PMID- 35301883 OWN - NLM STAT- MEDLINE DCOM- 20220509 LR - 20220509 IS - 1555-3892 (Electronic) IS - 0963-6897 (Print) IS - 0963-6897 (Linking) VI - 31 DP - 2022 Jan-Dec TI - 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. PG - 9636897221083863 LID - 10.1177/09636897221083863 [doi] LID - 09636897221083863 AB - 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. FAU - de Celis-Ruiz, Elena AU - de Celis-Ruiz E AUID- ORCID: 0000-0002-9224-9422 AD - Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital, Universidad Autonoma de Madrid), Madrid, Spain. FAU - Fuentes, Blanca AU - Fuentes B AD - Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital, Universidad Autonoma de Madrid), Madrid, Spain. FAU - Alonso de Lecinana, Maria AU - Alonso de Lecinana M AD - Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital, Universidad Autonoma de Madrid), Madrid, Spain. FAU - Gutierrez-Fernandez, Maria AU - Gutierrez-Fernandez M AD - Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital, Universidad Autonoma de Madrid), Madrid, Spain. FAU - Borobia, Alberto M AU - Borobia AM AD - Department of Clinical Pharmacology, Hospital la Paz Institute for Health Research-IdiPAZ (La Paz University Hospital, Universidad Autonoma de Madrid), Madrid, Spain. FAU - Gutierrez-Zuniga, Raquel AU - Gutierrez-Zuniga R AD - Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital, Universidad Autonoma de Madrid), Madrid, Spain. FAU - Ruiz-Ares, Gerardo AU - Ruiz-Ares G AD - Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital, Universidad Autonoma de Madrid), Madrid, Spain. FAU - Otero-Ortega, Laura AU - Otero-Ortega L AD - Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital, Universidad Autonoma de Madrid), Madrid, Spain. FAU - Laso-Garcia, Fernando AU - Laso-Garcia F AD - Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital, Universidad Autonoma de Madrid), Madrid, Spain. FAU - Gomez-de Frutos, Mari Carmen AU - Gomez-de Frutos MC AD - Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital, Universidad Autonoma de Madrid), Madrid, Spain. FAU - Diez-Tejedor, Exuperio AU - Diez-Tejedor E AD - Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital, Universidad Autonoma de Madrid), Madrid, Spain. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell Transplant JT - Cell transplantation JID - 9208854 SB - IM MH - *Brain Ischemia/drug therapy MH - Double-Blind Method MH - *Hematopoietic Stem Cell Transplantation MH - Humans MH - *Ischemic Stroke MH - *Mesenchymal Stem Cells MH - *Stroke/drug therapy MH - Treatment Outcome PMC - PMC8943307 OTO - NOTNLM OT - Acute ischemic stroke OT - allogeneic adipose tissue-derived mesenchymal stem cells OT - clinical trial OT - safety OT - stem cell therapy COIS- Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: BF reports grants from Spanish Ministry of Health and European Commission (Horizon2020 program) during the conduct of the study and from Daichi-Sankyo, Bayer, BMS-Pfizer, Novonordisk, and Novartis outside the submitted work. MG-F (CP15/00069; CPII20/00002) reports grants from the Spanish Ministry of Health and European Commission (Horizon2020 program) during the conduct of the study; nonfinancial support was received from Cellerix/Tigenix and Histocell, outside the submitted work. AMB reports grants from Instituto de Salud Carlos III, during the conduct of the study; personal fees from Mundipharma and Menarini outside the submitted work; and was Principal Investigator in Clinical Trials for GSK, Daiichi Sankyo, and Janssen. ED-T reports grants from the Spanish Ministry of Health and European Commission (Horizon2020 program) during the conduct of the study and nonfinancial support from Cellerix/Tigenix, Histocell, Daichi-Sankyo, Bayer, Sanofy Aventis, and Novartis outside the submitted work. EdC-R, RG-Z, MAdL, JCMV, GR-A, MCGdF (FI17/00188), FL-G (FI18/00026), and LO-O (CP20/00024) report nothing to disclose. EDAT- 2022/03/19 06:00 MHDA- 2022/05/10 06:00 PMCR- 2022/03/18 CRDT- 2022/03/18 08:39 PHST- 2022/03/18 08:39 [entrez] PHST- 2022/03/19 06:00 [pubmed] PHST- 2022/05/10 06:00 [medline] PHST- 2022/03/18 00:00 [pmc-release] AID - 10.1177_09636897221083863 [pii] AID - 10.1177/09636897221083863 [doi] PST - ppublish SO - Cell Transplant. 2022 Jan-Dec;31:9636897221083863. doi: 10.1177/09636897221083863.