Posts Tagged stem cells

[WEB PAGE] Differences Between Stem Cells and Somatic Cells

Any cell type in a multicellular organism, except germline cells, is called a somatic cell.

In contrast, stem cells are unspecialized cells with self-renewal capacity that can divide limitlessly to produce new stem cells, as well can differentiate to different cell types in the body.

What are Somatic Cells?

Somatic cells are diploid cells, which contain two pairs of chromosomes, one received from each parent. Any cell other than germ cells (sperm and egg), gametocytes (cells that divide to form germ cells), and undifferentiated stem cells are known as somatic cells.

Unlike germ cells, somatic cells are not capable of producing offspring; instead, they form all the internal organs and tissues and contribute significantly to their functionalities.

Meiosis. Cell division diagram. Image Credit: Designua / Shutterstock

Meiosis. Cell division diagram. Image Credit: Designua / Shutterstock

What are Stem Cells?

Stem cells are unspecialized cells with self-renewal capacity. They can divide through mitosis limitlessly to replenish other cell types of multicellular organisms throughout their life.

After stem cell division, each newly produced cell can either remain as a stem cell or differentiate to form any other cell type with more defined functions, such as muscle cell, blood cell, or neural cell.

Under special circumstances, differentiation of stem cells can also be induced to generate tissue- or organ-specific cell types with special functions. There are mainly two types of stem cells: embryonic stem cells, which are derived from embryos, and somatic or adult stem cells, which are undifferentiated cells residing in a tissue or organ along with other differentiated cells (somatic cells).

Stem cells. These inner cell mass from a blastocyst. Image Credit: Designua / Shutterstock

Stem cells. These inner cell mass from a blastocyst. Image Credit: Designua / Shutterstock

The major difference between embryonic and somatic stem cells is that embryonic stem cells have the potential to differentiate into all cell types of the body, as they are pluripotent stem cells (cells that are able to differentiate into three primary germ cell layers of the early embryo and, thus, into any cell type of the body); whereas, it is believed that somatic stem cells can differentiate only into different cell types present in the tissue of their origin.

Another type of genetically modified stem cell is induced pluripotent stem cell (iPSC). These cells are somatic stem cells that are genetically reprogramed to become like embryonic stem cells by inducing expressions of specific genes and other components necessary for maintaining embryonic stem cell properties.

Differences Between Stem Cells and Somatic Cells

Adult stem cells reside along with somatic cells in many tissues and organs, including peripheral blood, blood vessels, bone marrow, skeletal muscle, teeth, skin, gut, liver, ovary, testis, brain, and heart.

They are present in a small number and located in a specific area of each tissue called ‘stem cell niche’. Unlike somatic cells, stem cells can be in an inactive, non-dividing state for a long time until they are activated by certain internal or external signals, such as tissue injury or diseased conditions.

Adult stem cells can undergo normal differentiation pathways to give rise to specialized cells of the tissue wherein they are located. Some examples of stem cell differentiation into specialized somatic cells are as follows:

Hematopoietic stem cells – differentiate into all types of blood cells, including red blood cells (RBC), B lymphocytes, T lymphocytes, neutrophils, basophiles, eosinophils, monocytes, natural killer cells, and macrophages.

Mesenchymal stem cells – also known as bone marrow stromal stem cells, differentiate into different cell types, including bone cells, cartilage cells, fat cells, and stromal cells, that regulate blood production.

Neural stem cells – are present in the brain and can differentiate into three major brain cell types namely neurons (nerve cells), astrocytes, and oligodendrocytes.

Epithelial stem cells – are present in the epithelial lining of the gastrointestinal tract and can differentiate into different cell types, including absorptive cells, goblet cells, and enteroendocrine cells.

Skin stem cells – are of two types: epidermal stem cells that are found in the basal layer of the epidermis and can differentiate into keratinocytes; and follicular stem cells that are found at the base of hair follicles and can differentiate into both follicular cells and keratinocytes.

Besides normal differentiation, adult stem cells sometimes undergo transdifferentiation, a process by which stem cells from a particular tissue differentiate into specialized cell types of another tissue. For instance, stem cells from the brain that give rise to blood cells.

Despite many functional differences between stem cells and somatic cells, the ability of stem cells to differentiate into specialized cell types of the body has uncovered a potential way toward cell-based therapies, where stem cells can be used as a renewable source for replacing damaged somatic cells to treat many detrimental disorders, including heart diseases, stroke, spinal cord injury, macular degeneration, diabetes, rheumatoid arthritis, etc.

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[ARTICLE] Application of Stem Cells in Stroke: A Multifactorial Approach – Full Text

Stroke has a debilitating effect on the human body and a serious negative effect on society, with a global incidence of one in every six people. According to the World Health Organization, 15 million people suffer stroke worldwide each year. Of these, 5 million die and another 5 million are permanently disabled. Motor and cognitive deficits like hemiparesis, paralysis, chronic pain, and psychomotor and behavioral symptoms can persist long term and prevent the patient from fully reintegrating into society, therefore continuing to add to the costly healthcare burden of stroke. Regenerative medicine using stem cells seems to be a panacea for sequelae after stroke. Stem cell-based therapy aids neuro-regeneration and neuroprotection for neurological recovery in patients. However, the use of stem cells as a therapy in stroke patients still needs a lot of research at both basic and translational levels. As well as the mode of action of stem cells in reversing the symptoms not being clear, there are several clinical parameters that need to be addressed before establishing stem cell therapy in stroke, such as the type of stem cells to be administered, the number of stem cells, the timing of dosage, whether dose-boosters are required, the route of administration, etc. There are upcoming prospects of cell-free therapy also by using exosomes derived from stem cells. There are several ongoing pre-clinical studies aiming to answer these questions. Despite still being in the development stage, stem cell therapy holds great potential for neurological rehabilitation in patients suffering from stroke.


Stroke is one of the leading causes of chronic disability and mortality, with 102 million disability-adjusted life years lost annually (Steven, 2008). The Global Burden of Disease, Injuries, and Risk Factors Study (GBD 2015) reported a shift from communicable diseases toward non-communicable diseases like cerebrovascular events. While the incidence of stroke is decreasing in the developed world, it has peaked in low- and middle-income countries like India due to demographic transition and rapid shifts in the socioeconomic milieu (Thomson, 1998). The estimated adjusted prevalence rate of stroke is reported to have a range of 84–262/100,000 in rural and 334–424/100,000 in urban India (Wichterle et al., 2002Nagai et al., 2010).

The only neuroprotective agent developed for stroke in clinical use is recombinant tissue plasminogen activator (rtPA), which is employed for thrombolysis and has a therapeutic window of merely 3–4.5 h. There is thus a compelling need to develop therapeutic agents that extend beyond the first few hours after onset of stroke. This requires a paradigm shift to the usage of new strategies from neuroprotection to neuro-restoration that treat the injured or compromised brain tissue.

The majority of stroke survivors are left with some degree of disability, particularly upper limb dysfunction, despite several neurorehabilitation therapies. Physical therapy incorporating exercises, motor learning principles, motor cortex stimulation (using rTMS, TDCS), and assistive technologies aid the restoration of functional movements (Tae-Hoon and Yoon-Seok, 2012). The emergence of regenerative medicine has fueled interest across readers and clinicians to study its potential. Over the last decade, an enormous amount of work has been done exploring the potential of a variety of cells like adult stem cells, umbilical cord blood, and cells from adipose tissue and skin.

Pattern of Stroke Recovery

The recovery after stroke has been explained as a rich cascade of events encompassing cellular, molecular, genetic, demographic, and behavioral components. Such factors have been proven as covariates in therapeutic trials of restorative agents with a sound neurobiological basis. Advances in functional neuroimaging and brain mapping methods have provided a valuable parallel system of data collection for stroke recovery in humans. The recovery in a stroke-affected individual will largely depend on the size of lesion, the internal milieu of the brain injury, and the age and comorbid status of the patient. In general, the first epoch encompasses the initial hours after a stroke, when rapid change occurs in blood flow, edema, pro-inflammatory mechanisms. A second epoch is related to spontaneous behavioral recovery, which begins a few days after stroke onset and lasts several weeks. During this epoch, the brain is galvanized to initiate repair, as endogenous repair-related events reaching peak levels, suggesting a golden period for initiating exogenous restorative therapies. A third epoch begins weeks to months after stroke, when spontaneous behavioral gains have generally reached a plateau, and this stable state is responsive to many restorative interventions (Steven, 2008).

Mechanisms of Action of Stem Cells in Neural Repair

Stem cells have the capacity to differentiate into all types of cells. Exogenously administered cells appear to stimulate endogenous reparative processes and do not replace injured cerebral tissue. It was once thought that intravenously administered cells would home in on the injured site and replace the dead neurons, but the current ideology for the use of these cells holds that these cells release many trophic factors like VEGF, IGF, BDNF, and tissue growth factors that stimulate brain plasticity and recovery mechanisms. Upregulation of growth factors, prevention of ongoing cell death, and enhancement of synaptic connectivity between the host and graft are some of the common pathways through which intravenous stem cells work as “chaperones.” Regarding the timing of transplantation, preclinical studies have shown that cell therapy increases functional recovery after acute, sub-acute, and chronic stroke (Bliss et al., 2010), but few studies have compared different time windows, with differing results according to the model system and cell type studied. All of the possible modes of action of stem cells have been described in Figure 1.

Figure 1. Mechanisms of action of Mesenchymal Stem Cells in treating stroke.


Continue —->  Frontiers | Application of Stem Cells in Stroke: A Multifactorial Approach | Neuroscience

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[WEB SITE] Do You Know the 5 Types of Stem Cells?

Do You Know The 5 Types Of Stem Cells?

As you start to learn about stem cells, one of the most common questions to have is, “What types of stem cells exist?” There is not an agreed-upon number of stem cell types, because one can classify stem cells either by differentiation potential (what they can turn into) or by origin (from where they are sourced). This post is dedicated to explaining the five types of stem cells, based on differentiation potential.

5 Types of Stem Cells by Differentiation Potential

The five different types of stem cells discussed in this article are:

All stem cells that exist can be classified into one of five groups based on their differentiation potential. Each of these stem cell types is explored in greater detail below.

1. Totipotent (or Omnipotent) Stem Cells

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These stem cells are the most powerful that exist.

They can differentiate into embryonic, as well as extra-embryonic tissues, such as chorion, yolk sac, amnion, and the allantois. In humans and other placental animals, these tissues form the placenta.

The most important characteristic of a totipotent cell is that it can generate a fully-functional, living organism.

The best-known example of a totipotent cell is a fertilized egg (formed when a sperm and egg unite to form a zygote).

It is at or around four days post-fertilization that these cells begin to specialize into pluripotent cells, which as described below are flexible cell types, but cannot produce an entire organism. 

2. Pluripotent Stem Cells

The next most powerful type of stem cell is the pluripotent stem cell.

The importance of this cell type is that it can self-renew and differentiate into any of the three germ layers, which are: ectoderm, endoderm, and mesoderm. These three germ layers further differentiate to form all tissues and organs within a human being.

Embryonic Stem Cells

There are several known types of pluripotent stem cells.

Among the natural pluripotent stem cells, embryonic stem cells are the best example. However, a type of “human-made” pluripotent stem cell also exists, which is the induced pluripotent stem cell (iPS cell).

Induced Pluripotent Stem Cells

iPS cells were first produced from mouse cells in 2006 and human cells in 2007, and are tissue-specific cells that can be reprogrammed to become functionally similar to embryonic stem cells.

Because of their powerful ability to differentiate in a wide diversity of tissues and their non-controversial nature, induced pluripotent stem cells are well-suited for use in cellular therapy and regenerative medicine.

3. Multipotent Stem Cells

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Multipotent stem cells are a middle-range type of stem cell, in that they can self-renew and differentiate into a specific range of cell types.

An excellent example of this cell type is the mesenchymal stem cell (MSC).

Mesenchymal Stem Cells

Mesenchymal stem cells can differentiate into osteoblasts (a type of bone cell), myocytes (muscle cells), adipocytes (fat cells), and chondrocytes (cartilage cells).

These cells types are fairly diverse in their characteristics, which is why mesenchymal stem cells are classified as multipotent stem cells.

4. Oligopotent Cells

The next type of stem cells, oligopotent cells, are similar to the prior category (multipotent stem cells), but they become further restricted in their capacity to differentiate.

While these cells can self-renew and differentiate, they can only do so to a limited extent. They can only do so into closely related cell types.

An excellent example of this cell type is the hematopoietic stem cell (HSC).

Hematopoietic Stem Cells

HSCs are cells derived from mesoderm that can differentiate into other blood cells. Specifically, HSCs are oligopotent stem cells that can differentiate into both myeloid and lymphoid cells.

Myeloid cells include basophils, dendritic cells, eosinophils, erythrocytes, macrophages, megakaryocytes, monocytes, neutrophils, and platelets, while lymphoid cells include B cells, T cells, and natural kills cells.

5. Unipotent Stem Cells

Unipotent Stem Cells | Do You Know The 5 Types Of Stem Cells

Finally, we have the unipotent stem cells, which are the least potent and most limited type of stem cell.

An example of this stem cell type would be muscle stem cells.

Muscle Stem Cells

While muscle stem cells can self-renew and differentiate, they can only do so into a single cell type. They are unidirectional in their differentiation capacity.

Purpose of Classifying the Stem Cell Types

The purpose of these stem cell categories is to assess the functional capacity of stem cells based on their differentiation potential.

Importantly, each category has different stem cell research applications, medical applications, and drug development applications.

Different Types of Stem Cells | Do You Know The 5 Types Of Stem Cells

Watch this video and learn about the 5 types of stem cells:

If you found this article valuable, subscribe to BioInformant’s stem cell industry updates.

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In your opinion, which of the following types of stem cells have the best potential to form any tissue type? Mention them in the comments section below.

To learn more, view: Stem Cell Fact Sheet – Types of Stem Cells and their Use in Medicine


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[Infographic] 5 Types of Stem Cells by Differentiation Potential

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[TED Talk] The brain may be able to repair itself — with help | Jocelyne Bloch – YouTube

Through treating everything from strokes to car accident traumas, neurosurgeon Jocelyne Bloch knows the brain’s inability to repair itself all too well. But now, she suggests, she and her colleagues may have found the key to neural repair: Doublecortin-positive cells. Similar to stem cells, they are extremely adaptable and, when extracted from a brain, cultured and then re-injected in a lesioned area of the same brain, they can help repair and rebuild it. “With a little help,” Bloch says, “the brain may be able to help itself.”

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[WEB SITE] Is Stem Cell Therapy Effective?

Is stem cell therapy safe and effective?

Find out if the therapy is beneficial for a specific disease,
how and why it works and what the treatment involves

This article is written by Eremin Ilya – Vice Director for Science and Research at Swiss Medica clinic.

Swiss Medica specializes in the most cutting edge stem cell therapies for 8 years. Their head office is based in Switzerland and they have treatment centers in Russia, Moscow and Serbia, Belgrade.
As a result, patients have seen a halt in the progression and/or symptoms of a vast array of diseases, such as arthritis, diabetes, multiple sclerosis, autism, Parkinson’s and other hard to treat diseases.

What are stem cells?
Stem cells are the unique types of cells that are able to replicate itself and to launch the regeneration processes. Stem cells are circulating into the body and looking for damaged areas to repair them. They are also able to put out the inflammation.

This helps to eliminate the cause of the disorders, to reduce its symptoms or even to get a full recovery, depends on the initial condition. And the most important, stem cell treatment is a gentle way of healing that is safe and side-effect free in most cases.

When you undergo cell-based treatment, you get 100+ million viable stem cells in one dose. Cells are harvested from the patient’s body and then cultivated to this quantity. Donated stem cells can be also used for immediate treatment.

Not for all cases, but there is a high percentage of getting health improvements that can be reached in variety diseases.


What are the expected results?
Using stem cells in therapy helps to reduce symptoms and can even stop or reverse the progression of some diseases, mostly autoimmune and/or diseases associated with tissue damage. These types of cells trigger the healing process and help to:

– relieve inflammation;
– reduce pain;
– repair wounds and damaged tissues;
– stimulate the formation of neurons and new blood vessels;
– restore lost functions;
– eliminate the signs of aging.

Depending on the patient’s condition, we use cell products based on autologous (patient’s own) or donor cells. Activated stem cells can be administered in several ways, depending on the purpose of the therapy, the disease, and the patient’s condition (IV, intrathecal, intramuscular, retrobulbar or local injection).


It is important to understand that stem cells are not a guaranteed cure for every disease.The patient may be denied stem cell procedures for various reasons. The effectiveness of the therapy for a particular disease depends on multiple factors: duration of the illness, age of the patient, the existence of chronic conditions, hereditary predisposition, lifestyle, etc.

Applying only stem cells for some cases may be not enough. Cell therapy works more effectively when combined with other therapeutic methods that help decrease inflammation, restore mobility, activate the tissue repair process


How do stem cells work?
The main therapeutic effect of stem cells is their ability to produce cytokines and growth factors in the intercellular space. These special chemicals are able to activate the regenerative functions of distant cells and promote tissue recovery. This mechanism is called paracrine regulation.

Cytokines help block the signals of inflammation in various diseases, including autoimmune processes [1]. An important feature of these signal molecules is that their concentrations may be regulated by inflammation and may be strictly limited by the stage of tissue regeneration. We can boost the production of cytokines using cell products based on stromal cells, leading to improved function of the damaged tissue.

When stem cells are introduced into a patient’s body during therapy, they circulate in the blood system until they are attracted to proteins secreted around inflamed or damaged tissue. Stem cells then rush to that injured area and start producing:
– various growth factors (promoting tissue recovery);
– chemokines (helping cells to migrate);
– adhesion molecules (regulating cell interactions at the molecular level).

How the procedure is carried out?
First, the patient undergoes a full examination to determine the current state of health. Then specialist makes a conclusion about the appropriateness and expected effects of therapy.
Next, the question is whether self-sourced or donor stem cells will be used. In the first case, the biopsy is performed and stromal cells are isolated from the patient’s own biomaterial. Then the harvested cells are cultivated to the required volume. Usually, this takes 3-4 weeks depending on the proliferative potential of the MMSCs. After that, the cultivated cells can be used for therapy or stored in a cryobank for an unlimited period of time. In the case of donor cells, the cell product can be used immediately in the initial treatment.

The use of cell products is carried out under medical supervision. The volume of cell mass required for treatment is calculated depending on the patient’s body weight. Before use, a test for sterility and infectious/bacteriological safety is carried out. Then a passport of the cell product is drawn up. This passport indicates the name of the cell product, the source of cells, date of extraction, cells characteristics, description of final product formulation, etc.

When the cell product is ready for use, it can be administered in several ways, depending on the purpose of therapy, the disease, and the patient’s condition:

  • IV drip;
  • Intramuscularly;
  • Intrathecal (spinal tap);
  • Retrobulbar (in the eye area);
  • Locally (cutaneous covering, joint, cavernous bodies of the penis, etc.).

What are the indications, contraindications and side effects?

Treatment with cell products is usually appealed in cases where the standard therapy of the underlying disease is not adequately effective or is associated with complications.

Before therapy, it is necessary to exclude contraindications for cell treatment, including:
– Previous bad experience with cell products;
– Any acute infectious disease;
– Cancer or a precancerous condition;
– Stroke or transient ischemic attack in the last 3 months;
– Deviations of some indicators in blood tests;
– Mental disorders and addictions;
– Contraindications to anesthesia and/or high risk of bleeding and/or pathological processes in the area of the proposed biopsy (does not exclude the possibility of using donor cell products);
– Pregnancy and lactation, and some others.

Along with the expected improvements in cell therapy, unwanted side effects are rare and include allergic and pyrogenic posttransfusion reactions (short-term fever), which are both easily managed.

In a majority of cases, it is possible to decline the manifestations of the disease, weaken pain symptoms, and correct the function that was affected. The therapies generally improve the standard of living.

Safety of stem cell therapy
The procedures are usually well tolerated in the majority of patients. Clinical trial results confirmed the safety of local injections and treatment with MMSCs from the perspective of tumor formation after a follow-up period [6]. Individual intolerance (short-term fever), while rare, cannot be excluded. Swiss Medica specialists will monitor your condition for safer and more beneficial results. [2], [3].
When it comes to improvement?
It usually takes a few weeks or months until transplanted cells start to fully take effect, although the first improvements can be felt in the days after administration. Often, reduced pain, enhanced mobility of affected joints, improved energy and activity, improved indicators of diagnostic tests can be realized relatively quickly.

Transplanted stem cells are active for 3 months on average, 6 months as a maximum. After this period, the stem cells are no longer active, but the processes started by them continue. A complex effect is possible where not only the manifestations of the underlying disease are reduced, but also the general condition of the patient is improved.

Your doctor may recommend you to seek a second consultation after 3 and/or 6 months after cell introduction in order to assess the effectiveness of the therapy. To achieve a greater and more persistent effect, the therapy can be repeated after a recommended period of time. […]


For more visit site —->  Swiss Medica Article – Is Stem Cell Therapy Effective?

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[WEB SITE] Can Stem Cells be Used to Treat Epilepsy?

The primary pathogenesis of genetic forms of epilepsy is an abnormal expression of certain receptors in the brain that lead to an enhanced excitation and reduced inhibition. Some cases occur following oxygenation deprivation during birth.

Other later-life forms of epilepsy may be attributed to damage to the brain e.g. stroke, brain tumours, traumatic brain injury, drug misuse or a brain infection.

To date, there are several key treatment strategies to help people have fewer seizures. Predominantly, anti-epileptic drugs are used to treat the frequency and severity of epilepsy. However, these have to be taken routinely, and are not a long-term solution. They also have many undesired side-effects. However, anti-epileptic drugs may not work for everyone, therefore other treatments are used, including surgery and dietary modifications (e.g. keto-diet). Therefore, the need to find effective long-term solutions is needed to treat epilepsy.

Epileptic seizure. Image Credit: Rainer Fuhrmann / Shutterstock

Epileptic seizure. Image Credit: Rainer Fuhrmann / Shutterstock

What are Stem Cells?

Stem cells are cells that have the ability to develop into different specialised cell types of the body. Most cells in the body are post-mitotic, meaning they are unable to divide and grow into new types of tissues. However, stem cells are able to divide after periods of no apparent activity and are able to transform into different body cell types, including muscle cells, nerve cells and blood cells.

Embryonic stem cells. Illustration Credit: Nobeastsofierce / Shutterstock

Embryonic stem cells. Illustration Credit: Nobeastsofierce / Shutterstock

Traditionally, stem cells were only able to be isolated from embryos (animal and human) and some adult somatic stem cells, such as those found in e.g. bone marrow. However, due to advances in science and technology, adult cells taken from tissues such as e.g. skin, are now able to be reprogrammed into stem-cell like cells called induced pluripotent stem cells (iPSCs). These iPSCs may be able to function in very similar ways to those previously only obtainable through embryo donation.

iPSCs can be genetically manipulated to form a variety of different body cells e.g. neurons and muscle cells. However, much more work is needed before iPSCs can be used to replace dysfunctional cells within the body, though many advances have been made, especially in animal studies, including successful replacement of damaged heart cells with lab grown heart cells from the animals.

Can Stem Cells be Used to Treat Epilepsy?

As most cases of epilepsy can be attributed to receptor expression differences within the brain (due to mutations), correcting these may in theory reduce the likelihood of electrical seizures developing in the brain.

In addition, during status epilepticus, the excitation overload sometimes kills neurons, especially within the hippocampus. This can actually worsen the condition over time and lead to the development of temporal lobe epilepsy (TLE). Whilst anti-epileptic medication may treat the seizures, the damage caused to the temporal lobe is often irreversible and permanent, and current therapies do not address this.

As previously discussed, the reduction in inhibition in the brain, primarily due to loss of GABA-ergic interneurons, coupled with increased excitation of neurons, is key in the development of epilepsy including TLE.

Scientists therefore have speculated that enhancing inhibition by GABA-neurons may alleviate status epilepticus due to renewed inhibitory balance.

A study by Upadhya and colleagues (published in 2019 in PNAS); aimed to investigate whether iPSCs grafted into the brain of rats could reduce seizures and reverse damage in the hippocampus. They found that medial ganglionic eminence (MGE) cells derived from human-derived iPSCs, grafted into the hippocampus successfully reduced the frequency of seizures and reduced GABA-ergic neuronal loss.

Furthermore, there was an improvement to cognition and mood. Although this study was performed in rats, the implications of this research has far reaching potential to be used clinically.

Another study, a Phase I clinical trial in 22 patients, using autologous mesenchymal stem cells in epilepsy patients was shown to reduce overall seizure frequency (published in Advances in Medical Sciences by Hlebokazov and colleagues in 2017). Stem cells were obtained from patients’ own bone marrow, and administered intravenously and through a single injection into the spinal cord. After 1 year, 3 out of 10 patients achieved complete remission (no seizures) and another 5 patients that previously did not respond to drugs began to respond favourably. No side effects were observed in any of the patients.

This study is promising and showed a good safety profile for the patients. It appears that stem cells were associated with  alleviation of pathological hallmarks as well as the symptoms of epilepsy. Though this was only a Phase I trial with a very small cohort, additional controlled trials with placebos are needed in a larger cohort to make any definitive conclusions on the efficacy and safety.

In summary, stem cell based therapies, show promising results in the treatment of diseases including epilepsy. Animal and clinical studies have shown the remarkable efficacy of stem cells’ regenerative properties. However, larger clinical trials are needed before stem cell therapy can become routine. It is also expensive with therapies starting at around $5,000-$8,000 per treatment, though they can be as expensive as $25,000. In the UK, the NHS does not offer stem cell therapy routinely, only for a very small number of people in designated centres for diseases such as MS.

In the United States, the only type of stem cell therapy that has been extensively studied and approved for human treatment involves use of hematopoietic stem cells for patients with certain types of cancer.


  1., 2019. Epilepsy.
  2., 2019. Stem Cell Information.
  3. Upadhya et al, 2019. Human induced pluripotent stem cell-derived MGE cell grafting after status epilepticus attenuates chronic epilepsy and comorbidities via synaptic integration. PNAS. 116(1):287-96.
  4. Hlebokazov et al, 2017. Treatment of refractory epilepsy patients with autologous mesenchymal stem cells reduces seizure frequency: An open label study. Adv Med Sci. 62(2):273-279.

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Last Updated: Jul 5, 2019

Osman Shabir


Written by

Osman Shabir

Osman is a Neuroscience PhD Research Student at the University of Sheffield studying the impact of cardiovascular disease and Alzheimer’s disease on neurovascular coupling using pre-clinical models and neuroimaging techniques.


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[ARTICLE] Cell-Based Therapies for Stroke: Are We There Yet? – Full Text

Stroke is the second leading cause of death and physical disability, with a global lifetime incidence rate of 1 in 6. Currently, the only FDA approved treatment for ischemic stroke is the administration of tissue plasminogen activator (tPA). Stem cell clinical trials for stroke have been underway for close to two decades, with data suggesting that cell therapies are safe, feasible, and potentially efficacious. However, clinical trials for stroke account for <1% of all stem cell trials. Nevertheless, the resources devoted to clinical research to identify new treatments for stroke is still significant (53–64 million US$, Phase 1–4). Notably, a quarter of cell therapy clinical trials for stroke have been withdrawn (15.2%) or terminated (6.8%) to date. This review discusses the bottlenecks in delivering a successful cell therapy for stroke, and the cost-to-benefit ratio necessary to justify these expensive trials. Further, this review will critically assess the currently available data from completed stroke trials, the importance of standardization in outcome reporting, and the role of industry-led research in the development of cell therapies for stroke.



Stroke has a devastating effect on the society worldwide. In addition to its significant mortality rate of 50% as reported in 5-year survival studies (1), it affects as many as 1 in 6 people in their lifetimes, and is the leading cause of disability worldwide (2). A stroke results in a complex interplay of inflammation and repair with effects on neural, vascular, and connective tissue in and around the affected areas of the brain (3). Therefore, sequelae of stroke such as paralysis, chronic pain, and seizures can persist long term and prevent the patient from fully reintegrating into society. Stroke therefore remains the costliest healthcare burden as a whole (4). In 2012, the total cost of stroke in Australia was estimated to be about $5 billion with direct health care costs attributing to $881 million of the total (5).

Unfortunately, treatment options for stroke are still greatly limited. Intravenous recombinant tissue plasminogen activator (tPA) and endovascular thrombectomy (EVT) are currently the only effective treatments available for acute stroke. However, there is only a brief window of opportunity where they can be successfully applied. EVT is performed until up to 24 h of stroke onset (6), while tPA is applied within 4.5 h of stroke onset. Notably, the recent WAKE-UP (NCT01525290) (7) and EXTEND (NCT01580839) trials have shown that this therapeutic window can be safely extended to 9 h from stroke onset. Furthermore, advancements in acute stroke care and neurorehabilitation have shown to be effective in improving neurological function (8). However, there are no treatments that offer restoration of function and as a result, many patients are left with residual deficits following a stroke. Cell-based therapies have shown promising results in animal models addressing the recovery phase following stroke (9). This is encouraging as currently, there are no approved treatment options addressing the reversal of neurological damages once a stroke has occurred (10).

The majority of data from animal studies and clinical trials demonstrate the therapeutic potential of stem cells in the restoration of central nervous system (CNS) function (1112), applicable to neurodegenerative diseases as well as traumatic brain injury. Transplanted stem cells were reportedly able to differentiate into neurons and glial cells, whilst supporting neural reconstruction and angiogenesis in the ischemic region of the brain (13). Previous work demonstrated the ability of mesenchymal stem cells (MSCs) to differentiate into neurons, astrocytes (14), endothelial cells (1516), and oligodendrocyte lineage cells (17) such as NG2-positive cells (18in vitro, and undergo neuronal or glial differentiation in vivo (19). Bone marrow-derived mesenchymal stem cells (BMSCs) have shown potential to differentiate into endothelial cells in vitro (20). Additionally, both BMSCs and adipose stem cells (ASCs) have been shown to demonstrate neural lineage differentiation potential in vitro (2123). Furthermore, stem cells are able to modulate multiple cell signaling pathways involved in endogenous neurogenesis, angiogenesis, immune modulation and neural plasticity, sometimes in addition to cell replacement (3). The delivery of stem cells from the brain, bone marrow, umbilical cord, and adipose tissue, have been reported to reduce infarct size and improve functional outcomes regardless of tissue source (9). While these were initially exciting reports, they raise the question as to the validity of the findings to date since these preclinical reports are almost uniformly positive. The absence of scientific skepticism and robust debate may in fact have negated progress in this field.

Cell-based therapies have been investigated as a clinical option since the 1990s. The first pilot stroke studies in 2005 investigated the safety of intracranial delivery of stem cells (including porcine neural stem cells) to patients with chronic basal ganglia infarcts or subcortical motor strokes (2425). However, since the publication of these reports, hundreds of preclinical studies have shown that a variety of cell types including those derived from non-neural tissues can enhance structural and functional recovery in stroke. Cell therapy trials, mainly targeted at small cohorts of patients with chronic stroke, completed in the 2000s, showed satisfactory safety profiles and suggestions of efficacy (10). Current treatments such as tPA and EVT only have a narrow therapeutic window, limited efficacy in severe stroke and may be accompanied by severe side effects. Specifically, the side effects of EVT include intracranial hemorrhage, vessel dissection, emboli to new vascular territories, and vasospasm (26). The benefit of tPA for patients with a severe stroke with a large artery occlusion can vary significantly (27). This is mainly due to the failure (<30%) of early recanalisation of the occlusion. Thus, despite the treatment options stroke is still a major cause of mortality and morbidity, and there is need for new and improved therapies.

Stem cells have been postulated to significantly extend the period of intervention and target subacute as well as the chronic phase of stroke. Numerous neurological disorders such as Parkinson’s disease (1228), Alzheimer’s disease (29), age-related macular degeneration (30), traumatic brain injury (31), and malignant gliomas (32) have been investigated for the applicability of stem cell therapy. These studies have partly influenced the investigation of stem cell therapies for stroke. A small fraction of stem cell research has been successfully translated to clinical trials. As detailed in Table 1, most currently active trials use neuronal stem cells (NSCs), MSCs or BMSCs (3537), including conditionally immortalized neural stem-cell line (CTX-DP) CTX0E03 (38), neural stem/progenitor cells (NSCs/NPSCs) (e.g., NCT03296618), umbilical cord blood (CoBis2, NCT03004976), adipose (NCT02813512), or amnion epithelial cells (hAECs, ACTRN 1261800076279) (39).

Table 1. Challenges and bottlenecks of stem cell therapy and clinical trials using stem cells (3334).



Continue —>  Frontiers | Cell-Based Therapies for Stroke: Are We There Yet? | Neurology

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[FEATURE] The Role of PTs in Regenerative Medicine – PT in Motion

Physical therapists are playing a key role in the rehabilitation of patients who undergo regenerative procedures such as stem cell therapy and platelet-rich plasma injections.

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Kristin Bowne, PT, DPT, MS, clearly remembers the day in 2011 when she received the email that changed her career.

“It was an invitation to the First Annual Symposium on Regenerative Rehabilitation at the University of Pittsburgh,” she notes. The symposium, the message explained, would explore the emerging role of physical therapy in regenerative medicine, a field that focuses on treatment interventions including stem cell therapy and bio-scaffolding to repair, replace, or regenerate impaired or nonfunctional human tissue.

“I’d been in orthopedics and sports medicine for more than 20 years, and it just so happened that when I got that email I was thinking about what to do next—how my career might evolve,” Bowne says. “So, I flew out to Pennsylvania and went to the conference. It was so intriguing and exciting! I knew I’d found it. This was the future, and I wanted to be part of it.”

Fast-forward 5 years. Bowne’s growing outpatient private practice, Kristin Bowne Physical Therapy in Scotts Valley, California, bills itself as “the premier rehabilitation clinic for emerging regenerative therapies,” and as a center for clinical research into the field’s newest methods.

Her business “still is a general orthopedic, community-based practice,” Bowne notes, but each year she sees more and more patients and clients who come to her office immediately after having undergone regenerative procedures to address ailments such as joint pain, osteoarthritis (OA), and annular tears (rips in the tough exterior of an intervertebral disc). “Often, they’re opting for these procedures as an alternative to joint-replacement surgery,” she explains. “They’ll get the procedure done, then come in to start rehab the very next day.”

One recent patient, for example, arrived at Bowne’s clinic less than 24 hours after having received an injection to his knee consisting of autologous bone marrow aspirate concentrate (BMAC) combined with platelet-rich plasma (PRP). Another patient—a former professional tennis player—had just been given stem cell injections to treat advanced OA in his knees and hips.

For these patients and others like them, “you definitely have to take a different approach” from that taken with a typical patient, Bowne says. “First, we always try to see them before the procedure, if possible, to clear up their biomechanics and train them in exercises that will help them prepare. It’s also important to maintain an open line of communication with their regenerative physicians. You also need to understand molecular biology, the science behind these procedures, and how different treatments affect healing times and the healing process.”

In the years Bowne has worked with individuals who have undergone regenerative therapy, she has developed her own regenerative rehabilitation program. It combines appropriate rest, biomechanical loading, tissue mobilization, and a number of procedure-specific protocols designed to guide patients through the recovery process and ultimately help them regain function. Now, she says, she’s spending part of her time teaching these principles and therapeutic techniques to other physical therapists (PTs) around the country (including, notably, members of the physical therapy department at the Mayo Clinic in Rochester, Minnesota).

“Here’s the problem,” Bowne says. “The consensus is that rehab is vital to success” after regenerative interventions such as PRP and stem cell transplantation, “but many physicians—understandably, I think—still are very cautious regarding to whom they’ll send their patients after these procedures. While they recognize that rehab is important, they’re not yet convinced that PTs have the training, or are sufficiently well-versed in the specifics of what is needed by a regenerative patient, to make that referral for physical therapy.”

Her goal in teaching others what she knows, she says, is to facilitate collaborative relationships between regenerative physicians and PTs. It also is to ensure that individuals who undergo regenerative procedures can receive the rehab they need from a local PT. “I have some patients who travel a long way to get here, but that’s really not best for them,” she says. “What’s best is for them to connect with therapists in their area who know what they’re doing and are keeping up on the science as it evolves.”

“Exciting” Times

The evolving science has been a point of interest for Steve Wolf, PT, PhD, FAPTA, FAHA, since at least 2002. During a session at APTA’s annual conference that year, he cited regenerative medicine and rehabilitation as being among several emerging fields that one day would have a place within the physical therapy profession. Wolf, a professor in the physical therapy division in the Department of Rehabilitation Medicine at Emory University in Atlanta, later helped organize a group of APTA members and non-physical therapists to start a project named FiRST (Frontiers in Rehabilitative Science Technologies), which identified 4 areas, including regenerative rehab, as critical to the future of rehabilitation.

FiRST, Wolf explains, is about building the profession’s knowledge base—through research and education—in technology-focused fields. (The other 3 areas under the FiRST umbrella are bioengineering, genomics, and telehealth). And when it comes to regenerative rehabilitation, Wolf says, that base is growing “exponentially” every year. “Just to give you an idea” he says, “there were almost as many papers published in the last 18 months under the title ‘regenerative rehabilitation’ as a subcategory of ‘regenerative medicine’ as there had been in all the years prior. So the knowledge is increasing, and it’s all very promising. But,” he adds, “we’re still not there yet.”

The profession isn’t “there yet,” Wolf continues, because, while regenerative therapy is “beginning to enter the classroom, and we’re seeing the topic more at various symposia,” the evidence for the effectiveness of regenerative rehabilitation “has not yet been convincingly ascertained.” He’s not saying, he emphasizes, that PTs shouldn’t be trusted by physicians to help guide individuals within this patient population back to health. It’s just that the therapeutic strategies and principles around these medical procedures won’t gain widespread acceptance until they’re “completely understood by the PT community.”

Fabrisia Ambrosio, PT, MPT, PhD, agrees. Ambrosio, assistant professor in the Department of Physical Medicine and Rehabilitation at the University of Pittsburgh and director of the Cellular Rehabilitation Laboratory there, says, “We have started to see regenerative rehabilitation gain momentum, especially in terms of recognizing that we need more research in the area.”

To that end, last September, the Alliance for Regenerative Rehabilitation Research and Training (AR3T)—a group Ambrosio founded with her colleagues at Pitt’s McGowan Institute for Regenerative Medicine and individuals at several other institutions—was awarded a $1.1 million grant by the National Institutes of Health’s National Center for Medical Rehabilitation Research.

AR3T, Ambrosio explains, was created to bring regenerative-medicine scientists together with rehabilitation researchers and clinicians. “Our goals are twofold,” she says. “First, to focus on education—on giving rehabilitation clinicians foundational knowledge in regenerative medicine and stem cell biology,” as well as the tools they need to collaborate effectively with regenerative-medicine physicians. The second goal is to promote that collaboration in the laboratory, “so clinicians and scientists are working side-by-side to develop and answer the research questions that will continue to move the field forward.”

Ambrosio, who back in 2011 was responsible for the email that Kristin Bowne and other PTs received—and who now is preparing for the fifth iteration of the same event, to be held this October at Emory—calls the current climate around regenerative medicine and physical therapy’s role in regenerative rehabilitation “exciting.” The basic-science community, she notes, citing as evidence a recent article in the cell and molecular biology-focused magazine The Scientist, “is now recognizing how vital rehab is to this area.”

That piece, published in December, stated that stem cell therapies and tissue engineering were “nearing medical prime time” and that a “growing number of scientists, clinicians, and physical therapists now are taking an interdisciplinary approach to rehabilitation, pairing exercise with technologies that regenerate bone, muscle, cartilage, ligaments, nerves, and other tissues.” In the article, Carmen Perez-Terzic, a cardiovascular disease researcher at the Mayo Clinic, described regenerative rehabilitation as “a new future” and predicted “It’s going to explode in the next 5 or 10 years.”

When she hears such statements, Ambrosio says, she knows regenerative rehab has turned the corner. “For a cell-biology publication to be making the case that, ‘Hey, you should be thinking about these rehabilitative protocols and how they’ll play a role in translating your technologies,’ I think that shows we’re making great progress.”

Working Outside the Boundaries

Further evidence of this progress can be found at MD Anderson Cancer Center in Houston, where Kimberly Presson, PT, DPT, CLT-LANA, is a senior PT in the Department of Rehabilitation Services. She works primarily with patients who are there to receive treatment for diseases and disorders that include leukemia, lymphoma, and myeloma. Almost all those patients have had stem cell transplants, she notes—including autologous transplants, in which the patient’s own stem cells are collected prior to chemotherapy and/or radiation, then transplanted back, and allogeneic transplants, in which patients are given healthy donor stem cells in place of their own.

The typical stem cell hematology patient remains at the hospital for about a month. (MD Anderson can accommodate up to 96 patients at any time.) “Our first goal,” Presson says, “is to see to them as early as we can,” before the transplant, if possible. She and her colleagues—including other PTs, physical therapist assistants (PTAs), and occupational therapists—lead patients through several low-intensity group-exercise classes each week. All patients who are able to attend are encouraged to do so. “We know that, given their chemotherapy, we’re probably not going to make them a lot stronger, but we do want them to maintain the strength they have,” Presson says.

Patients who are too weak to take the classes are seen 1-on-1, she adds. “Usually for them it’s about working on their mobility and core strength, and getting them out of bed, even if it’s just to a chair.”

Posttransplant, physical therapy interventions continue—provided the patient is able. “These patients have totally depleted bone marrow with very low hemoglobin and platelets, so we have to pay attention to their blood counts,” Presson says. “They also are fatigued. They’re so tired from the treatment, we do only as much as they can tolerate, even if it’s just a few exercises in the bed.”

Determining the approach to take with each patient requires close collaboration with other health care professionals, Presson adds. “We’re in constant communication with either the nurses or the clinical nurse leaders,” she says. “If somebody is on my list for the group class but hasn’t come in 2 or 3 days, and I haven’t seen that individual walking, the nurse probably has some valuable information for me.”

Every Thursday, all those involved in patient care spend an hour together in interdisciplinary rounds discussing each case. “The clinical nurse leaders, PTs, OTs, the dietician, the case manager, the social worker, the chaplain, ethicists, we all sit down together and make sure everyone knows exactly what’s going on.”

Presson first worked with stem cell patients during a clinical rotation at MD Anderson when she was still was in school. After graduation she spent 2 years in outpatient orthopedics before returning when a position opened up. “Most of what I’ve learned about regenerative rehabilitation has been through on-the-job training,” she says. “At a lot of the hematology courses a PT might attend, they’ll tell you that you can’t work with a patient with a hemoglobin under 8 or a platelet count of less than 10. Well, if my patients have a hemoglobin in the mid- to high-7s, that’s a good day,” Presson says. “So, we’re basically working outside the boundaries of what most clinicians would consider normal. But we have to. If we don’t, the patient’s condition probably will get worse.”

The physicians with whom she works, she says, “really appreciate the benefit of our services” and recognize that undergoing therapy immediately posttransplant may be the key to their patients’ success. “Just the other day, I heard a physician telling all of his patients, ‘Look, you really need to listen to this lady and do what she asks. She’s the one who’s going to get you out of here,'” Presson notes.

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Justin Reyes, PTA, works with patients at the MD Anderson Cancer Center under the supervision of Kimberly Presson, PT, DPT, CLT-LANA.

Justin Reyes, PTA, who works with many of Presson’s patients before and after they’ve had their stem cell transplants, has heard similar advice from MD Anderson’s physicians. He also has seen the determination of those patients. “The majority of them come in here just hoping for a second chance. They’re motivated; they want to return to their lives. Sometimes they’re tired. Or maybe they’re nauseated. But they’re usually still willing to do something, even if they can’t do a lot.”

Reyes describes working with a recent patient who “we really thought wasn’t going to make it.” But then, Reyes says, “that individual was able to push and work and go to rehab, then on to outpatient care, and now the patient is back home in El Paso. That kind of thing makes this job rewarding.”

PRP: Simulating Injuries To Stimulate Healing

While advances such as tissue-engineered bladders and vascular grafts are the headline-grabbers of regenerative medicine, far more common is a simpler procedure involving injections of platelet-rich plasma (PRP). “The number of physicians performing PRP procedures has skyrocketed during the past 5 years,” says Stephen Clark, PT, DPT, MBA, OCS, president and founder of Athletic Physical Therapy in Los Angeles. He’s even had them himself, he notes—in both Achilles tendons and in a knee.

The procedure, Clark explains, involves a series of injections of a patient’s own blood after it has gone through a multistage centrifugation process that increases platelet concentration to 5-8 times its normal level. Once administered, the PRP simulates an injury at the site of the injection, which in turn triggers the body’s healing response.

“One of the issues with PRP is that there’s no single protocol all physicians follow,” Clark says. “Different physicians will use different platelet concentrations for the same injury. Some add activators [to stimulate healing], while others don’t. One might do 30 fenestrations [at the injection site] while another does 5.” Thus, he notes, while “everybody calls it PRP, it’s highly variable.”

Still, Clark says, the patients he sees—primarily athletes who are dealing with nagging pain in their elbows, knees, hips, and Achilles tendons—”seem to benefit” from the procedure. “But they do need rehab afterward,” he adds, “because it’s just as if they’ve been hurt again.” For that reason, he explains, he treats most of his PRP patients as though they’ve experienced an acute injury.

“We basically start at square one, and if I can get to them before their injection, that’s even better.” For those patients, he’ll typically try to stimulate blood flow to the injured area using instrument-assisted soft-tissue massage. The idea is to “provoke the injury a little” to kickstart the inflammatory response.

After the injection is administered, it’s usually recommended that the patient rest for a few days before starting physical therapy. “Once they come in, the main thing”—and the biggest difference between a PRP patient and most others—”is that, instead of trying to calm the inflammatory process down, we’re trying to help it continue for 7-10 days.” Clark varies therapy according to each patient’s tolerance, but he also works closely with physicians to ensure that everyone is on the same page. “They’re often pretty conservative,” he says. “They don’t want you to go too fast.”

In his own case, Clark says, his PRP injections have worked as advertised for almost 10 years. And he’s seen similar results with his patients—watching them, after they’ve finished their therapy, return to the sports and activities they love. “Insurance companies still consider PRP to be experimental,” he notes, explaining that all of his PRP patients pay cash. But Clark believes it won’t be long before the procedure is covered.

Stem Cells in Orthopedics

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Angie Garrett, PT, MS, OCS, BCB-PMD, and a patient.

Angie Garrett, PT, MS, OCS, BCB-PMD,works closely with a physician to provide a new option for patients with osteoarthritis of the shoulder.

Garrett, a PT at Mission Hospital in Mission Viejo, California, explains, “Studies have shown that when stem cells are injected into an area of damaged tissue, they begin to differentiate into the tissue of the designated area, resulting in the regrowth of new healthy tissue. These procedures typically are minimally invasive,” she notes, resulting in lower risks than with a conventional surgery. In the case of the shoulder, she adds, “the theory is that stem cells will differentiate into articular cartilage, returning the joint to a healthier functional state.”

She works with orthopedic surgeon Ralph Venuto, MD, of Newport Beach, California. He performs an arthroscopic debridement on the patient prior to surgery to optimize the stem cell uptake by the joint surface. The patient also undergoes a course of rehabilitative physical therapy. “The purpose of physical therapy,” Garrett explains, “is to regain as much mobility in the shoulder as possible, control pain and inflammation, and prevent the development of adhesive capsulitis, effectively preparing the shoulder for the stem cell procedure.”

Venuto uses both PRP and stem cells from adipose tissue, as well as hematopoietic stem cells from the bone marrow. Then comes a waiting period. “Immediate physical therapy will accomplish nothing,” Garrett explains, because the stem cells first must transform into new, regenerated cartilage. Physical therapy often begins about 2 weeks after the procedure and will continue for several months afterward.

“Although it is in its infancy, regenerative medicine is providing an additional option to these patients,” Garrett says. “Not surprisingly, these procedures are creating a nascent physical therapy niche, as well.”

Kristin Bowne sees a similar future for stem cell injections and other regenerative techniques, and the PT-led rehabilitation that often follows the procedures.

“This stuff works,” she says. “Biological injections combined with rehabilitation are generating positive results,” she says. It saves people time, it saves them from lost work, and it’s going to start replacing a lot of surgical procedures.” She recently saw a patient who had both PRP and stem cell injections to heal tears in her thoracic spine. As the patient’s PT, Bowne’s job now is to “restore the altered biomechanics she’s developed due to compensatory patterns, so that she doesn’t wear the discs down again.”

Regenerative medicine offers “a great opportunity for rehab science, and for PTs to get involved.” Bowne says. “It’s so exciting—like this big, wide-open door.”

Chris Hayhurst is a freelance writer.

For More Information

American Physical Therapy Association

Regenerative Rehabilitation:

Learning Center: Course LMS-426: Physical Therapy and the Future of Regenerative Medicine (

Alliance for Regenerative Rehabilitation Research and Training (AR3T)

International Society for Stem Cell Research

Mayo Clinic Center for Regenerative Medicine

McGowan Institute for Regenerative Medicine

National Institutes of Health’s National Center for Medical Rehabilitation Research


Hello, my name is Sheila and I am interested in getting information on the type of physical therapy that you are doing for a stem cell treatment. I received stem cell/ Platelet injections for my hip four months ago. I started physical therapy about a month after the procedure. I’m their first stem cell patient. Their style is not typical but again if I could get some information of what you are doing it would be very helpful. I’m just a bit discouraged. Trying to do everything I can before making the decision for a hip replacement. I live in northern Ca. at least 4 hours away from you. Is there someone close to Ukiah or Santa Rosa That you could recommend. Thank you for any advise, Sheila Fetzer
Posted by Sheila Fetzer on 5/25/2016 11:39:22 PM
It’s important to distinguish the putative effects of stem cell therapy from the possibility that stem cells develop into other cell types, eg, cartilage or connective tissue. In many other fields, injections of various kinds of stem cells have produced positive results, but the stem cells themselves were gone in less than a week. That raises the possibility that stem cells may elicit growth factors themselves or from other cells in the region, cause other cells to proliferate and differentiate, and a do a variety of other functions, but without the stem cells themselves differentiating and providing desired functions. This is not to say that stem cells may not do so in certain circumstances, but improved structure and function can not necessarily be attributed to stem cells differentiating and becoming part of the local cellular make up. To show that, one would need to be able to identify progeny of the stem cells, such as by using some sort of molecular tag.
Posted by Dan Keller on 7/13/2016 2:18:33 PM
This is for Sheila Fetzer on 5/25/2016 comment and question. Sheila I would like to know how your hips are progressing after your PRP shots as I’m thinking of using the same procedure.
Posted by Fred Sistilli on 2/14/2017 4:07:12 PM


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[BLOG POST] Where does the controversial finding that adult human brains don’t grow new neurons leave ongoing research?

Scientists have known for about two decades that some neurons – the fundamental cells in the brain that transmit signals – are generated throughout life. But now a controversial new study from the University of California, San Francisco, casts doubt on whether many neurons are added to the human brain after birth.

As a translational neuroscientist, this work immediately piqued my interest. It has direct implications for the research my lab does: We transplant young neurons into damaged brain areas in mice in an attempt to treat epileptic seizures and the damage they’ve caused. Like many labs, part of our work is based on a foundational belief that the hippocampus is a brain region where new neurons are born throughout life.

If the new study is right, and human brains for the most part don’t add new neurons after infancy, researchers like me need to reconsider the validity of the animal models we use to understand various brain conditions – in my case temporal lobe epilepsy. And I suspect other labs that focus on conditions including drug addiction, depression and post-traumatic stress disorder are thinking about what the UCSF study means for their investigations, too.

In the brain of a baby who died soon after birth, there are many new neurons (green in this image) in the hippocampus. Sorrells et alCC BY-ND

When and where are new neurons born?

No doubt, the adult human brain is able to learn throughout life and to change and adapt – a capability brain scientists call neuroplasticity, the brain’s ability to reorganize itself by rewiring connections. Yet, a central dogma in the field of neuroscience for nearly 100 years had been that a child is born with all the neurons she will ever have because the adult brain cannot regenerate neurons.

Just over half a century ago, researchers devised a way to study proliferation of cells in the mature brain, based on techniques to incorporate a radioactive label into new cells as they divide. This approach led to the startling discovery in the 1960s that rodent brains actually could generate new neurons.

Neurogenesis – the production of new neurons – was previously thought to only occur during embryonic life, a time of extremely rapid brain growth and expansion, and the rodent findings were met with considerable skepticism. Then researchers discovered that new neurons are also born throughout life in the songbird brain, a species scientists use as a model for studying vocal learning. It started to look like neurogenesis plays a key role in learning and neuroplasticity – at least in some brain regions in a few animal species.

Even so, neuroscientists were skeptical that many nerve cells could be renewed in the adult brain; evidence was scant that dividing cells in mammalian brains produced new neurons, as opposed to other cell types. It wasn’t until researchers extracted neural stem cells from adult mouse brains and grew them in cell culture that scientists showed these precursor cells could divide and differentiate into new neurons. Now it is generally well accepted that neurogenesis takes place in two areas of the adult rodent brain: the olfactory bulbs, which process smell information, and the hippocampus, a region characterized by neuroplasticity that is required for forming new declarative memories.

Adult neural stem cells cluster together in what scientists call niches – hotbeds for cultivating the birth and growth of new neurons, recognizable by their distinctive architecture. Despite the mounting evidence for regional growth of new neurons, these studies underscored the point that the adult brain harbors only a few stem cell niches and their capacity to produce neurons is limited to just a few types of cells.

With this knowledge, and new tools for labeling proliferating cells and identifying maturing neurons, scientists began to look for postnatal neurogenesis in primate and human brains.

What’s happening in adult human brains?

Many neuroscientists believe that by understanding the process of adult neurogenesis we’ll gain insights into the causes of some human neurological disorders. Then the next logical step would be trying to develop new treatments harnessing neurogenesis for conditions such as Alzheimer’s disease or trauma-induced epilepsy. And stimulating resident stem cells in the brain to generate new neurons is an exciting prospect for treating neurodegenerative diseases.

Because neurogenesis and learning in rodents increases with voluntary exercise and decreases with age and early life stress, some workers in the field became convinced that older people might be able to enhance their memory as they age by maintaining a program of regular aerobic exercise.

However, obtaining rigorous proof for adult neurogenesis in the human and primate brain has been technically challenging – both due to the limited experimental approaches and the larger sizes of the brains, compared to reptiles, songbirds and rodents.

Researchers injected a compound found in DNA, nicknamed BrdU to identify brand new neurons in human adult hippocampus – but the labeled cells were extremely rare. Other groups demonstrated that adult human brain tissue obtained during neurosurgery contained stem cell niches that housed progenitor cells that could generate new neurons in the lab, showing that these cells had an inborn neurogenic capacity, even in adults.

But even when scientists saw evidence for new neurons in the brain, they tended to be scarce. Some neurogenesis experts were skeptical that evidence based on incorporating BrdU into DNA was a reliable method for proving that new cells were actually being born through cell division, rather than just serving as a marker for other normal cell functions.

Further questions about how long human brains retain the capacity for neurogenesis arose in 2011, with a study that compared numbers of newborn neurons migrating in the olfactory bulbs of infants versus older individuals up to 84 years of age. Strikingly, in the first six months of life, the baby brains contained lots of chains of young neurons migrating into the frontal lobes, regions that guide executive function, long-range planning and social interactions. These areas of the human cortex are hugely increased in size and complexity compared to rodents and other species. But between 6 to 18 months of age, the migrating chains dwindled to a thin stream. Then, a very different pattern emerged: Where the migrating chains of neurons had been in the infant brain, a cell-free gap appeared, suggesting that neural stem cells become depleted during the first six months of life.

Questions still lingered about the human hippocampus and adult neurogenesis as a source for its neuroplasticity. One group came up with a clever approach based on radiocarbon dating. They measured how much atmospheric ¹⁴C – a radioactive isotope derived from nuclear bomb tests – was incorporated into people’s DNA. This method suggested that as many as 700 new cells are added to the adult human hippocampus every day. But these findings were contradicted by a 2016 study that found that the neurogenic cells in the adult hippocampus could only produce non-neuronal brain cells called microglia.

Rethinking neurogenesis research

Now the largest and most comprehensive study conducted to date presents even stronger evidence that robust neurogenesis doesn’t continue throughout adulthood in the human hippocampus – or if it does persist, it is extremely rare. This work is controversial and not universally accepted. Critics have been quick to cast doubt on the results, but the finding isn’t totally out of the blue.

So where does this leave the field of neuroscience? If the UCSF scientists are correct, what does that mean for ongoing research in labs around the world?

Because lots of studies of neurological diseases are done in mice and rats, many scientists are invested in the possibility that adult neurogenesis persists in the human brain, just as it does in rodents. If it doesn’t, how valid is it to think that the mechanisms of learning and neuroplasticity in our model animals are comparable to those in the human brain? How relevant are our models of neurological disorders for understanding how changes in the hippocampus contribute to disorders such as the type of epilepsy I study?

In my lab, we transplant embryonic mouse or human neurons into the adult hippocampus in mice, after damage caused by epileptic seizures. We aim to repair this damage and suppress seizures by seeding the mouse hippocampus with neural stem cells that will mature and form new connections. In temporal lobe epilepsy, studies in adult rodents suggest that naturally occurring hippocampal neurogenesis is problematic. It seems that the newborn hippocampal neurons become highly excitable and contribute to seizures. We’re trying to inhibit these newborn hyperexcitable neurons with the transplants. But if humans don’t generate new hippocampal neurons, then maybe we’re developing a treatment in mice for a problem that has a different mechanism in people.

Perhaps our species has evolved separate mechanisms for neuroplasticity, distinct from those used by species such as rats and mice. One possibility is that there are other sites in the human brain where neurogenesis occurs – its a big structure and more exploration will be necessary. If it turns out to be true that the human brain has a diminished capacity for neurogenesis after birth, the finding will have important implications for how neuroscientists like me think about tackling brain disorders.

Perhaps most importantly, this work underscores how crucial it is to learn how to increase the longevity of the neurons we do have, born early in life, and how we might replace or repair neurons that become damaged.

via Where does the controversial finding that adult human brains don’t grow new neurons leave ongoing research?


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