Efficacy and Safety of Intravenous Mesenchymal Stem Cells for Ischemic Stroke

Abstract

ObjectiveTo test whether autologous modified mesenchymal stem cells (MSCs) improve recovery in patients with chronic major stroke.MethodsIn this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct within 90 days of symptom onset were assigned, in a 2:1 ratio, to receive preconditioned autologous MSC injections (MSC group) or standard treatment alone (control group). The primary outcome was the score on the modified Rankin Scale (mRS) at 3 months. The secondary outcome was to further demonstrate motor recovery.ResultsA total of 39 and 15 patients were included in the MSC and control groups, respectively, for the final intention-to-treat analysis. Mean age of patients was 68 (range, 28–83) years, and mean interval between stroke onset to randomization was 20.2 (range, 5–89) days. Baseline characteristics were not different between groups. There was no significant difference between the groups in the mRS score shift at 3 months (p = 0.732). However, secondary analyses showed significant improvements in lower extremity motor function in the MSC group compared to the control group (change in the leg score of the Motricity Index, p = 0.023), which was notable among patients with low predicted recovery potential. There were no serious, treatment-related adverse events.ConclusionsIntravenous application of preconditioned, autologous MSCs with autologous serum was feasible and safe in patients with chronic major stroke. MSC treatment was not associated with improvements in the 3-month mRS score, but we did observe leg motor improvement in detailed functional analyses.Classification of evidenceThis study provides Class III evidence that autologous mesenchymal stem cells do not improve 90-day outcomes in patients with chronic stroke.Trial registrationclinicaltrials.gov Identifier: NCT01716481.

Mesenchymal Stromal Cells Perspective: New Potential Therapeutic for the Treatment of Neurological Diseases

“…The recent clinical reports using MSCs for the treatment of ischemic stroke are summarized in Table 1 . Some studies have reported on the safety and feasibility of BM-MSCs in patients with ischemic stroke injury [ 48 , 49 , 50 , 51 ]. In these clinical trials, patients received intravenous injections of BM-MSCs, and an improvement in neurological functioning was observed, while no treatment-related adverse events were seen.…”

Strategies to Improve the Efficiency of Transplantation with Mesenchymal Stem Cells for the Treatment of Ischemic Stroke: A Review of Recent Progress

“…No significant improvement was observed in a randomized controlled intravenous phase II trial [ 122 ]. In 2021, Chung et al reported that MSC treatment is not associated with improvements in the 3-month modified Rankin score, and their study provided class III evidence that autologous MSCs do not improve 90-day outcomes in patients with chronic stroke [ 123 ].…”

Combination of Stem Cells and Rehabilitation Therapies for Ischemic Stroke

“…Robust functional improvement was found in patients undergoing the therapy [ 89 ]. Similarly, autologous modified MSC administration was safe and effective in chronic major stroke patients [ 90 ]. Compared to the control group, patients with MSC treatment demonstrated substantial mitigation of lower extremity motor impairments [ 90 ].…”

“…Similarly, autologous modified MSC administration was safe and effective in chronic major stroke patients [ 90 ]. Compared to the control group, patients with MSC treatment demonstrated substantial mitigation of lower extremity motor impairments [ 90 ]. Of note, phase I/II clinical trials conducted by Bang et al showed an increase in Barthel’s index 90 days post-stroke when given IV BM-MSCs to patients [ 91 ].…”

“…This incongruity is likely due to multiple factors such as: suboptimal dosage, lack of use of clinical-grade cell lines, and timing of stem cell administration [ 9 , 16 , 93 ]. With considerable evidence demonstrating clinical safety of MSCs in stroke patients [ 9 , 31 , 90 ], future clinical research should further evaluate the efficacy of MSCs as a stroke therapy and examine how stem cell therapeutic mechanisms can be better utilized to see greater preclinical translation to clinical investigations.…”