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

Abstract

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.

Bone Marrow-Derived IL-1Ra Increases TNF Levels Poststroke

“…Our results support the view that the immunosuppressive capacity of BM-derived MSCs is not innate but most likely induced under inflammatory conditions in situ [85]. In our view, there is no doubt that BM-derived MSCs have a beneficial effect in stroke as reviewed for both rodent and human stroke trials [1,65,[86][87][88]; however, further details are needed in order to understand the mechanism of these cells poststroke fully.…”

[18F]FDG-labelled stem cell PET imaging in different route of administrations and multiple animal species

“…These considerations are further fueled by the fact that clinical trials e.g. on cerebral infarction and chronic ischemic heart disease and stem cell therapy have yielded mixed results 39 , 40 . Beyond cardiovascular disease, recent studies also demonstrated that transplanted MSCs are mainly trapped in the lung, e.g.…”

Current status of ischemic stroke treatment: From thrombolysis to potential regenerative medicine

“…using IV transplantation of allogenic MSCs was successful, showing significant behavioral improvement in their Barthel Index (BI) scores, which measures a patient's ability to function in daily life [ 42 ]. Fortunately, all these clinical trials were safe in patients, showing significant improvement from older clinical trials that had severe adverse effects [ 43 ]. The most likely reason for the inconsistent results is the small size of these trials, which leads to a risk of bias [ 43 ].…”

“…Fortunately, all these clinical trials were safe in patients, showing significant improvement from older clinical trials that had severe adverse effects [ 43 ]. The most likely reason for the inconsistent results is the small size of these trials, which leads to a risk of bias [ 43 ]. Two phase III clinical trials are currently being conducted (MASTERS-2 and TREASURE), so a better understanding of MSC efficacy may be reached soon [ 44 ].…”