Final Results of Allogeneic Adipose Tissue–Derived Mesenchymal Stem Cells in Acute Ischemic Stroke (AMASCIS): A Phase II, Randomized, Double-Blind, Placebo-Controlled, Single-Center, Pilot Clinical Trial

Abstract

Acute ischemic stroke is currently a major cause of disability despite improvement in recanalization therapies. Stem cells represent a promising innovative strategy focused on reduction of neurologic sequelae by enhancement of brain plasticity. We performed a phase IIa, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. Patients aged ≥60 years with moderate to severe stroke (National Institutes of Health Stroke Scale [NIHSS] 8–20) were randomized (1:1) to receive intravenous adipose tissue–derived mesenchymal stem cells (AD-MSCs) or placebo within the first 2 weeks of stroke onset. The primary outcome was safety, evaluating adverse events (AEs), neurologic and systemic complications, and tumor development. The secondary outcome evaluated treatment efficacy by measuring modified Rankin Scale (mRS), NIHSS, infarct size, and blood biomarkers. We report the final trial results after 24 months of follow-up. Recruitment began in December 2014 and stopped in December 2017 after 19 of 20 planned patients were included. Six patients did not receive study treatment: two due to technical issues and four for acquiring exclusion criteria after randomization. The final study sample was composed of 13 patients (4 receiving AD-MSCs and 9 placebo). One patient in the placebo group died within the first week after study treatment delivery due to sepsis. Two non-treatment-related serious AEs occurred in the AD-MSC group and nine in the placebo group. The total number of AEs and systemic or neurologic complications was similar between the study groups. No injection-related AEs were registered, nor tumor development. At 24 months of follow-up, patients in the AD-MSC group showed a nonsignificantly lower median NIHSS score (interquartile range, 3 [3–5.5] vs 7 [0–8]). Neither treatment group had differences in mRS scores throughout follow-up visits up to month 24. Therefore, intravenous treatment with AD-MSCs within the first 2 weeks from ischemic stroke was safe at 24 months of follow-up.

Stem cell-based therapy for human diseases

“… 205 A phase II, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial using AT-MSCs in the treatment of acute ischemic stroke published a data set that supports the safety of the therapy, although patients who received AT-MSCs showed a nonsignificant improvement after 24 months of follow-up. 206 In all of the above studies, the safety of using either AT-MSCs or UC-MSCs was evaluated, and no significant reactions were reported after infusion.…”

“…205 A phase II, randomized, doubleblind, placebo-controlled, single-center, pilot clinical trial using AT-MSCs in the treatment of acute ischemic stroke published a data set that supports the safety of the therapy, although patients who received AT-MSCs showed a nonsignificant improvement after 24 months of follow-up. 206 In all of the above studies, the safety of using either AT-MSCs or UC-MSCs was evaluated, and no significant reactions were reported after infusion. Therefore, based on the number of recovered patients posttransplantation and the number of recruited patients in largescale trials using BM-MSCs, it seems that BM-MSCs are the prominent cells in regard to treating neurodegenerative disease with potentially good outcomes (Table 1).…”

Clinical application of mesenchymal stem cell in regenerative medicine: a narrative review

“…The results of that study represented the absolute change of LEVF within 12 months, improvement in cardiac function, induction of remodeling and regeneration, and improvement in quality of life [ 108 ]. Recently, Celis-Ruiz and coworkers conducted a study in which intravenous administration of adipose MSCs within the first 2 weeks of ischemic stroke onset is safe at 24 months of follow-up [ 106 ]. In a study conducted by Hare et al [ 112 ], 37 non-ischemic dilated cardiomyopathy patients were divided into two groups and received 10 × 10 7 allogeneic and autologous BMSCs.…”

Editing a gateway for cell therapy across the blood–brain barrier

“…50 , 54 , 56 , 57 , 59 , 60 However, in other studies, the IV injection of adipose-derived-MSCs, BM-MSCs or BM-MNCs for treating acute, subacute or chronic stroke have not achieved significant improvement in any of the studied functional outcome scores compared to the control cohort. 48 , 49 , 51 , 52 , 55 A biodistribution clinical study determined that IV administration of BM-MNCs resulted in lung entrapment and low cell counts in brain which might explain the failure observed in clinical trials ( Table 3 and Supplementary Table 1 ). 84 However, the determination of the optimal cell type, cell dose and injection timing are also crucial for improving the recovery of stroke patients following endovascular cell administration.…”