[ARTICLE] A Review of Stem Cell Therapy for Acquired Brain Injuries and Neurodegenerative Central Nervous System Diseases – Full Text

Abstract

Cell-based therapies have been the subject of much discussion regarding their potential role in enhancing central nervous system function for a number of pathologic conditions. Much of the current research has been in preclinical trials, with clinical trials in the phase I or I/II stage. Nevertheless, there is considerable interest in the public about the potential regenerative role that stem cells may have in improving function for these neurologic conditions. This review will describe the different types of stem cells that are available, review their possible effects, and discuss some of the variables that investigators need to consider when designing their studies. Current clinical research in the areas of stroke, traumatic brain injury, and neurodegenerative diseases (amyotrophic lateral sclerosis and Parkinson disease) will be reviewed. As this article is aimed at a rehabilitation audience, outcome measures, and the role of concurrent rehabilitation therapies will also be mentioned.

Introduction

Potential Roles That Stem Cells May Play in Regeneration

Stem cells may exert positive effects on the recovery process in a number of ways. Some cells have the ability to replicate and play a direct role in the repair of damaged neural tissue. These neural progenitor or neural stem cells (NSCs) may differentiate into different cell types and may be subsumed to roles of previously damaged or lost neurons. Such cells have been studied in a number of clinical conditions, but ethical issues have arisen, primarily because embryonic or fetal tissues have often been used. As these are allogeneic transplants, efforts must be taken to suppress the immune response, which may lead to complications. Additionally, concerns regarding tumorigenicity are greater for these cells because of their replicative ability [1]. Adult neural stem cells can be found in some areas of the human brain including the subventricular zone and the hippocampal dentate gyrus [2]. These are pluripotent cells that can replicate and differentiate based on intrinsic and environmental factors. They also have the ability to migrate, and differentiation may be driven by their ultimate location [3]. There is the possibility that these cells can be cultured and engineered to carry out specific functions based on modulation of these factors, but much needs to be learned in order to achieve this goal [4].

Induced pluripotent stem cells (IPSCs) can also be generated from adult cells. They are reprogrammed by transcription factors into a more embryonic state. It is possible to perform this in an autologous fashion (the patient is the source for his or her IPSCs), although this can be difficult as this is an inefficient process that may take time to produce adequate cell numbers. Some concerns regarding tumorigenicity also exist for this strategy. Mesenchymal stem cells (MSCs) are another option for cell-based therapies. Autologous and allogeneic sources for these cells are available. These cells usually do not differentiate into neural cells. Rather, it is believed that their primary role in neural recovery is by producing trophic factors into their environment to stimulate endogenous neurogenesis and repair as well as modulating inflammation [5]. MSCs do not appear to have the potential to become tumorigenic. However, they may have an immunosuppressive effect that, among other complications, might increase the risk of tumor formation [6].

The United States Food and Drug Administration (FDA) has on several occasions produced policies that have provided guidance regarding the use of these products to both protect consumers and support the ongoing research and development of regenerative medicine products in general. The stem cells discussed here are regenerative medicine therapies, and there are procedures that must be followed in clinical trials. The FDA has recently made efforts to try to “fast-track” some regenerative medicine therapies, especially those that address “serious diseases and conditions” [7].[…]

 

Continue —> A Review of Stem Cell Therapy for Acquired Brain Injuries and Neurodegenerative Central Nervous System Diseases – PM&R

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