Intracerebral transplantation of MRI-trackable autologous bone marrow stromal cells for patients with subacute ischemic stroke.

Autor:	Kawabori M; Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan. Electronic address: kawabori@med.hokudai.ac.jp., Kuroda S; Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan., Shichinohe H; Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, Hokkaido 060-8638, Japan., Kahata K; Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, Hokkaido 060-8638, Japan., Shiratori S; Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido 060-8638, Japan., Ikeda S; Department of Rehabilitation, Hokkaido University Hospital, Sapporo, Hokkaido 060-8638, Japan., Harada T; Department of Diagnostic Imaging, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan., Hirata K; Department of Diagnostic Imaging, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan., Tha KK; Global Center for Biomedical Science and Engineering, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido 060-8638, Japan., Aragaki M; Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, Hokkaido 060-8638, Japan., Terasaka S; Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan., Ito YM; Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, Hokkaido 060-8638, Japan., Nishimoto N; Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, Hokkaido 060-8638, Japan., Ohnishi S; Laboratory of Molecular and Cellular Medicine, Hokkaido University Graduate School of Pharmacology, Sapporo, Hokkaido 060-8638, Japan., Yabe I; Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-8638, Japan., Kudo K; Department of Diagnostic Imaging, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan., Houkin K; Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan., Fujimura M; Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
Jazyk:	angličtina
Zdroj:	Med (New York, N.Y.) [Med] 2024 May 10; Vol. 5 (5), pp. 432-444.e4. Date of Electronic Publication: 2024 Mar 27.
DOI:	10.1016/j.medj.2024.02.009
Abstrakt:	Background: Ischemic stroke is one of the leading causes of death and neurological disability worldwide, and stem cell therapy is highly expected to reverse the sequelae. This phase 1/2, first-in-human study evaluated the safety, feasibility, and monitoring of an intracerebral-transplanted magnetic resonance imaging (MRI)-trackable autologous bone marrow stromal cell (HUNS001-01) for patients with subacute ischemic stroke. Methods: The study included adults with severe disability due to ischemic stroke. HUNS001-01 cultured with human platelet lysates and labeled with superparamagnetic iron oxide was stereotactically transplanted into the peri-infarct area 47-64 days after ischemic stroke onset (dose: 2 or 5 × 10 7 cells). Neurological and radiographic evaluations were performed throughout 1 year after cell transplantation. The trial was registered at UMIN Clinical Trial Registry (number UMIN000026130). Findings: All seven patients who met the inclusion criteria successfully achieved cell expansion, underwent intracerebral transplantation, and completed 1 year of follow-up. No product-related adverse events were observed. The median National Institutes of Health Stroke Scale and modified Rankin scale scores before transplantation were 13 and 4, which showed improvements of 1-8 and 0-2, respectively. Cell tracking proved that the engrafted cells migrated toward the infarction border area 1-6 months after transplantation, and the quantitative susceptibility mapping revealed that cell signals at the migrated area constantly increased throughout the follow-up period up to 34% of that of the initial transplanted site. Conclusions: Intracerebral transplantation of HUNS001-01 was safe and well tolerated. Cell tracking shed light on the therapeutic mechanisms of intracerebral transplantation. Funding: This work was supported by the Japan Agency for Medical Research and Development (AMED; JP17bk0104045 and JP20bk0104011). Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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