Clinical outcome and safety of stem cell therapy for ischemic stroke: A systematic review and meta-analysis

Abstract

Background: Several reports on stem cell administration have emerged proving it to be an ideal therapeutic approach for improving neurological functions in ischemic stroke patients. However, some studies also show disappointing results, with some reporting no statistically significant improvements among several different parameters. Several challenges also arise relating to safety and nonscientific aspects, such as ethics.

Methods: We performed a systematic review and meta-analysis to evaluate the effect of stem cell therapy on the clinical outcomes of ischemic stroke patients. A systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A thorough literature search was conducted on PubMed, Scopus, and Cochrane databases. Articles were selected systematically based on the PRISMA protocol and reviewed completely. A total of 19 publications pertaining to stem cell therapy on the ischemic route were included and reviewed. Efficacy outcomes were measured with the National Institutes of Health Stroke Scale, modified Rankin Scale, or Barthel Index.

Results: The results of the meta-analysis indicate that the efficacy outcomes suggest favorable results after stem cell therapy, although not all study results are statistically significant. Stem cell therapy in stroke cases showed a better outcome than standard conservative therapy alone, although our analysis shows that many factors can influence this outcome, and significant effects can only be seen after several months.

Conclusion: The results of this study show promising and satisfying efficacy and a relatively low rate of serious adverse events.

Keywords: Clinical outcome; Ischemic stroke; Safety; Stem cell therapy.

Figure 1:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines flowchart.

Figure 2:

Result of ROBINS-I assessment. (a), Risk assessment of bias using ROBINS-I for nonrandomized studies in each study. (b), the proportion of bias risk assessment results using ROBINS-I for the nonrandomized study.

Figure 3:

Result of RoB 2 assessment. (a) Risk assessment of bias using RoB 2 for randomized studies in each study. (b) The proportion of bias risk assessment results using RoB 2 for the randomized study.

Figure 4:

Calculation of the mean difference in NIHSS scores after 6 months between stem cell therapy and control groups in three studies. The mean difference was statistically greater in the stem cell therapy group and this result was statistically significant (MD = −1.48; 95% CI −2.68–−0.28; P = 0.02; and I² = 83%).

Figure 5:

Calculation of the mean difference in mRS scores after 6 months between the stem cell therapy and control groups in three studies. The mean difference was statistically greater in the stem cell therapy group, although this result was not statistically significant (MD = −0.27; 95% CI −0.52–0.17; P = 0.33; and I² = 93%).

Figure 6:

Calculation of mean difference in BI scores after 6 months between stem cell therapy and control groups in three studies. The mean difference was statistically greater in the stem cell therapy group, although this result was not statistically significant (MD = −0.27; 95% CI −0.52–0.17; P = 0.33; and I² = 93%).

Figure 7:

Calculation of the mean difference in NIHSS scores after 12 months between the stem cell therapy and control groups in two studies. The mean difference was statistically greater in the stem cell therapy group, although this result was not statistically significant (MD = −1.17; 95% CI −4.69–2.36; P = 0.52; and I² = 96%).

Figure 8:

Calculation of the mean difference in mRS scores after 12 months between the stem cell therapy and control groups in two studies. The mean difference was statistically greater in the stem cell therapy group, and this result was statistically significant (MD = −0.53; 95% CI −0.92– −0.15; P = 0.007; and I² = 80%).

Figure 9:

Calculation of the mean difference in NIHSS scores after 24 months between the stem cell therapy and control groups in two studies. The mean difference was statistically greater in the stem cell therapy group, although this result was not statistically significant (MD = −0.12; 95% CI −2.81–2.58; P = 0.93; and I² = 90%).

Figure 10:

Calculation of the mean difference in mRS scores after 24 months between the stem cell therapy and control groups in two studies. The mean difference was statistically greater in the stem cell therapy group, although this result was not statistically significant (MD = −0.35; 95% CI −0.74–0.03; P = 0.07; and I² = 67%).

Figure 11:

Calculation of the mean difference in BI scores after 24 months between the stem cell therapy and control groups in two studies. The mean difference was statistically greater in the control group, although this result was not statistically significant (MD = −0.62; 95% CI −10.89–9.64; P = 0.93; and I² = 80%).