Meta-Analysis of the Safety and Efficacy of Stem Cell Therapies for Ischemic Stroke in Preclinical and Clinical Studies

Ouyang, Qian; Feng, Lei; Xie, Yong; Han, Jianbang; Zhang, Zhongfei; Feng, Zhiming; Su, Dazhuang; Zou, Xiaoxiong; Cai, Yuchen; Zou, Yuxiao; Tang, Yanping; Jiang, Xiao-dan

doi:10.1089/scd.2018.0218

Cited by 15 publications

(15 citation statements)

References 63 publications

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“…Fever, headache, and stroke recurrence were frequently reported cellrelated adverse effects in our review. But there was no significant difference compared with the control group according to previous results [13,14]. Antithrombotic treatment can reduce the risk of recurrent stroke, but only four RCTs and one NRSs reported antithrombotic treatment.…”

Section: Discussionmentioning

confidence: 70%

“…Since then, a number of clinical trials have been conducted to verify the efficacy and safety of stem cell-based therapies for ischemic stroke with different stem cell types, doses, and delivery routes at different phases of stroke [12]. But the outcomes in different stroke scales are inconsistent [13,14]. In this study, we attempted to investigate the effectiveness and safety of stem cell-based therapies for ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

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Stem cell-based therapies for ischemic stroke: a systematic review and meta-analysis of clinical trials

Dong

Tian

et al. 2020

Stem Cell Res Ther

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Recently, extensive researches about stem cell-based therapies for ischemic stroke have been published; our review evaluated the efficacy and safety of stem cell-based therapies for ischemic stroke. Our review was registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42019135805. Two independent observers searched PubMed, EMBASE, Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials), and Web of Science (Science Citation Index Expanded) for relevant studies up to 31 May 2019. We included clinical trials which compared efficacy outcomes (measured by National Institutes of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), or Barthel index (BI)) and safety outcomes (such as death and adverse effects) between the stem cell-based therapies and control in ischemic stroke. We performed random effect meta-analysis using Review Manager 5.3. Our review included nine randomized controlled trials (RCTs) and seven non-randomized studies (NRSs), involving 740 participants. Stem cell-based therapies were associated with better outcomes measured by NIHSS (mean difference (MD) − 1.63, 95% confidence intervals (CI) − 2.73 to − 0.53, I 2 =60%) and BI (MD 14.68, 95% CI 1.12 to 28.24, I 2 = 68%) in RCTs, and by BI (MD 6.40, 95% CI 3.14 to 9.65, I 2 = 0%) in NRSs. However, the risk of bias was high and the efficacy outcomes of RCTs were high heterogeneity. There was no significant difference in mortality between the stem cell group and the control group. Fever, headache, and recurrent stroke were the most frequently reported adverse effects. Our review shows that stem cell-based therapies can improve the neurological deficits and activities of daily living in patients with ischemic stroke.

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Stem cell-based therapies for ischemic stroke: a systematic review and meta-analysis of clinical trials

Dong

Tian

et al. 2020

Stem Cell Res Ther

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“…Their meta-analysis in the pre-clinical section did not assess functional outcome and focused only on neurological status improvement and structural outcomes. The results of their study showed a significant improvement in neurological status and structural outcomes in the cell therapy group [66]. Since most of the included studies in Vu et al, Lees et al, Sarmah et al and Ouyang et al meta-analyses were performed on the other types of MSCs (most BMSCs), the higher efficacy, which was observed in our study, can be related to the better biological activity of ADSCs compared to BMSCs in improvement of functional recovery after Stroke.…”

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Efficacy of adipose derived stem cells on functional and neurological improvement following ischemic stroke: a systematic review and meta-analysis

et al. 2020

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Background: The evidence on the efficacy of adipose derived stem cells (ADSCs) in the treatment of stroke is controversial. Therefore, the aim of present systematic review and meta-analysis is to evaluate the efficacy of ADSCs administration in the treatment of animal models of ischemic stroke. Methods: An extensive search was performed on electronic databases of Medline, Embase, Scopus, CENTRAL and Web of Science until December 31, 2018. Animal studies that used ADSCs in treatment of ischemic stroke were included. The data were recorded as mean and standard deviation and then a pooled standardized mean difference (SMD) with 95% confidence interval (95% CI) was reported. Results: Twenty articles were included in the present meta-analysis. It was observed that administration of ADSCs improves motor function (SMD = 2.52, 95% CI: 1.67 to 3.37, p < 0.0001) and neurological status (SMD = 2.05, 95% CI: 1.33 to 2.78, p < 0.0001) in animals following an ischemic stroke. Multivariate meta-regression showed the model of stroke induction (p = 0.017) and the number of transplanted cells (p = 0.007) affect the efficacy of ADSCs administration on motor function improvement following the stroke. Conclusion: Moderate to high levels of evidence indicate a strong efficacy of ADSCs transplantation on motor function and neurological improvement following ischemic stroke in animal models. However, no reports regarding the dose-response effect of ADSCs administration on stroke exist in the literature. As a result, further pre-clinical studies are recommended to be conducted on the matter.

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“…The migration, proliferation and differentiation of h-ESC-NPCs in the ischemic lesion has been confirmed in several studies. [28][29][30][31] On the other hand, this amount of transplanted cells cannot be differentiated to replace the damaged tissue in the ischemic region. So, they might apply their alterations via other mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Human embryonic derived neural progenitor cells improves neurological scores following brain ischemia/ reperfusion: Modulation of blood and brain tissue MicroRNA-210

Arab

Fanni

Nemati

et al. 2020

J. Contemp. Med. Sci.

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Objective: In this study, we evaluated the effects of human embryonic derived neural progenitor cells on neurological score, histopathological changes, and miRNA-210 as biomarkers of regeneration. Methods: The animals were randomly divided into the four groups: Sh (sham), MCAO (middle cerebral artery occlusion), MCAO+PBS, MCAO+Cell. One day after MCAO induction, embryonic derived neural progenitor cells (hESC-NPCsGFP) or PBS were injected intracerebroventriculary in MCAO+Cell or MCAO+PBS groups. On day 1, 2, 3, and 7 after ischemia induction, the neurological score was tested in each rat. At 48h, the expression of miRNA-210 was evaluated and 7 days after, the pathological assessments were performed by H&E staining. Results: Neurological score showed the promotion of functional recovery in MCAO+Cell group. Based on H&E staining, the percentage of neural death in ischemic region reduced in MCAO+Cell group. The miRNA-210 significantly upregulated in both brain and blood samples. Conclusion: According to the findings, hESC-NPCsGFP injection could up-regulate the miRNA-210 of tissue and blood to support the neuroprotective and regenerative effect of hESC-NPCsGFP in the ischemic lesion and improved the neurological score and reduce the neural death in ischemic region.

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Meta-Analysis of the Safety and Efficacy of Stem Cell Therapies for Ischemic Stroke in Preclinical and Clinical Studies

Cited by 15 publications

References 63 publications

Stem cell-based therapies for ischemic stroke: a systematic review and meta-analysis of clinical trials

Stem cell-based therapies for ischemic stroke: a systematic review and meta-analysis of clinical trials

Efficacy of adipose derived stem cells on functional and neurological improvement following ischemic stroke: a systematic review and meta-analysis

Human embryonic derived neural progenitor cells improves neurological scores following brain ischemia/ reperfusion: Modulation of blood and brain tissue MicroRNA-210

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