[Abstract] Controlled clinical trials of cell therapy in stroke: Meta-analysis at six months after treatment

Cell therapy is promising in experimental studies and has been assessed only in a few studies on humans.

To evaluate the effect of cell therapy in humans.

We included clinical trials with a control group that reported safety and efficacy six months following treatment. Quality was evaluated and clinical scales data were extracted. Quantitative analysis was based on the standardized means difference (SMD). Among 28 trials published from 1995 to 2016, nine studies (194 patients; 191 controls) were eligible. Publication biases were assessed with the funnel plot and pre-specified explanatory variables were tested with a group analysis and a meta-regression.

The overall quality was moderate. Cell therapy had a positive effect on the outcome (SMD: 0.57, 95% CI: 0.22–0.92; p = 0.002). The sensitivity analysis showed an upper level of effect size of 0.81 (95% CI: 0.34–1.27; p = 0.001) and a lower level of 0.455 (95% CI: 0.04–0.87; p = 0.03). None of the pre-specified explanatory variable was significantly correlated to outcome: age, ratio infarction/hemorrhage, delay from stroke to treatment, route of administration, cell type, randomization, and blinded outcome assessment. The significant heterogeneity (p = 0.03) was not explained by publication biases (p = 0.09) and was more likely due to methodological and quality differences between the trials.

This result suggests that cell therapy is beneficial in stroke and is expected to help in the designing of stem cells controlled clinical trials (CCT) in large populations.

1.Jauch EC, Saver JL, Adams HPJr, . Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke 2013; 44: 870947. Google Scholar CrossRef, Medline

2.Balami JS, Sutherland BA, Edmunds LD, . A systematic review and meta-analysis of randomized controlled trials of endovascular thrombectomy compared with best medical treatment for acute ischemic stroke. Int J Stroke 2015; 10: 11681178. Google Scholar Abstract
3.Jin K, Wang X, Xie L, . Evidence for stroke-induced neurogenesis in the human brain. Proc Natl Acad Sci USA 2006; 103: 1319813202. Google Scholar CrossRef, Medline
4.Favre I, Zeffiro TA, Detante O, Krainik A, Hommel M, Jaillard A. Upper limb recovery after stroke is associated with ipsilesional primary motor cortical activity: a meta-analysis. Stroke 2014; 45: 10771083.Google Scholar CrossRef, Medline
5.Murphy TH, Corbett D. Plasticity during stroke recovery: from synapse to behaviour. Nat Rev Neurosci 2009; 10: 861872. Google Scholar CrossRef, Medline
6.Parent JM, Vexler ZS, Gong C, Derugin N, Ferriero DM. Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol 2002; 52: 802813. Google Scholar CrossRef, Medline
7.Walker MR, Patel KK, Stappenbeck TS. The stem cell niche. J Pathol 2009; 217: 169180. Google Scholar CrossRef, Medline
8.Detante O, Jaillard A, Moisan A, . Biotherapies in stroke. Rev Neurol 2014; 170: 779798. Google Scholar CrossRef, Medline
9.Lees JS, Sena ES, Egan KJ, . Stem cell-based therapy for experimental stroke: a systematic review and meta-analysis. Int J Stroke 2012; 7: 582588. Google Scholar Link
10.Jeong H, Yim HW, Cho YS, . Efficacy and safety of stem cell therapies for patients with stroke: a systematic review and single arm meta-analysis. Int J Stem Cells 2014; 7: 6369. Google Scholar CrossRef, Medline
11.Wang Q, Duan F, Wang MX, Wang XD, Liu P, Ma LZ. Effect of stem cell-based therapy for ischemic stroke treatment: a meta-analysis. Clin Neurol Neurosurg 2016; 146: 111. Google Scholar CrossRef, Medline
12.Bang OY, Lee JS, Lee PH, Lee G. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 2005; 57: 874882. Google Scholar CrossRef, Medline
13.Rabinovitch SS, Seledtsov VI, Banul NV, . Cell therapy of brain stroke. Cell Tech Biol Med 2005; 1: 126128. Google Scholar
14.Kondziolka D, Steinberg GK, Wechsler L, . Neurotransplantation for patients with subcortical motor stroke: a phase 2 randomized trial. J Neurosurg 2005; 103: 3845. Google Scholar CrossRef, Medline
15.Bhasin A, Srivastava MV, Kumaran SS, . Autologous mesenchymal stem cells in chronic stroke. Cerebrovasc Dis Extra 2011; 1: 93104. Google Scholar CrossRef, Medline
16.Moniche F, Gonzalez A, Gonzalez-Marcos JR, . Intra-arterial bone marrow mononuclear cells in ischemic stroke: a pilot clinical trial. Stroke 2012; 43: 22422244. Google Scholar CrossRef, Medline
17.Bhasin A, Srivastava MV, Mohanty S, Bhatia R, Kumaran SS, Bose S. Stem cell therapy: a clinical trial of stroke. Clin Neurol Neurosurg 2013; 115: 10031008. Google Scholar CrossRef, Medline
18.Li ZM, Zhang ZT, Guo CJ, . Autologous bone marrow mononuclear cell implantation for intracerebral hemorrhage-a prospective clinical observation. Clin Neurol Neurosurg 2013; 115: 7276. Google Scholar CrossRef, Medline
19.Chen DC, Lin SZ, Fan JR, . Intracerebral implantation of autologous peripheral blood stem cells in stroke patients: a randomized phase ii study. Cell Transplant 2014; 23: 15991612. Google Scholar Medline
20.Prasad K, Sharma A, Garg A, . Intravenous autologous bone marrow mononuclear stem cell therapy for ischemic stroke: a multicentric, randomized trial. Stroke 2014; 45: 36183624. Google ScholarCrossRef, Medline
21.Langhorne P, Bernhardt J, Kwakkel G. Stroke rehabilitation. Lancet 2011; 377: 16931702. Google Scholar CrossRef, Medline

Source: Controlled clinical trials of cell therapy in stroke: Meta-analysis at six months after treatment – Mar 10, 2017



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