Cell transplantation is a promising treatment strategy for many neurological disorders, including stroke, which can target multiple therapeutic mechanisms in a sustained fashion. We investigated the ability of human mesenchymal stromal cells (MSCs) and MSC-derived SB623 cells to rescue neural cells via trophic support following an in vitro stroke model. Following oxygen glucose deprivation, cortical neurons or hippocampal slices were cocultured with either MSCs or SB623 cells separated by a semiporous membrane (prohibits cell-cell contact) or with MSC- or SB623 cell-conditioned medium. MSCs, SB623 cells, MSC-conditioned media, and SB623 cell-conditioned media all significantly reduced neural cell damage/death compared to untreated conditions, and the rescue effect of the conditioned media was dose dependent. We identified 11 neurotrophic factors secreted by MSCs and/or SB623 cells. This study emphasizes the importance of trophic support provided by marrow-derived cells, which likely contributes to the efficacy of cell therapy for brain injury.
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http://dx.doi.org/10.3727/096368910X494885 | DOI Listing |
Exp Neurol
January 2025
Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. Electronic address:
Ischemic stroke results in significant long-term disability and mortality worldwide. Although existing therapies, such as recombinant tissue plasminogen activator and mechanical thrombectomy, have shown promise, their application is limited by stringent conditions. Mesenchymal stem cell (MSC) transplantation, especially using SB623 cells (modified human bone marrow-derived MSCs), has emerged as a promising alternative, promoting neurogenesis and recovery.
View Article and Find Full Text PDFMol Ther
January 2025
Gladstone Institute of Neurological Disease, San Francisco, CA, USA; University of California, San Francisco, Department of Neurology, and the Kavli Institute for Fundamental Neuroscience, San Francisco, CA, USA; University of California, San Francisco, Neurosciences Graduate Program, San Francisco, CA, USA. Electronic address:
Allogeneic modified bone marrow-derived human mesenchymal stromal/stem cells (hMSC-SB623 cells) are in clinical development for the treatment of chronic motor deficits after traumatic brain injury and cerebral ischemic stroke. However, their exact mechanisms of action remain unclear. Here, we investigated the effects of this cell therapy on cortical network excitability, brain tissue, and peripheral blood at a chronic stage after ischemic stroke in a rat model.
View Article and Find Full Text PDFNeurology
October 2024
From the Department of Neurological Surgery (D.O.O.), University of Pittsburgh Medical Center, PA; New England Institute for Neurology and Headache (P.M.), Stamford, CT; Department of Neurosurgery (A.S.A.), Loma Linda University Medical Center, CA; Department of Neurosurgery (Y.K.), The University of Tokyo Hospital, Japan; Department of Neurosurgery (M.K.), Hokkaido University Hospital, Sapporo, Japan; Department of Neurology (S.C.C.), University of California, Los Angeles; Westview Clinical Research (A.L.), Placentia, CA; Department of Translational Neurosciences (S.K.), Providence Saint John's Health Center, Santa Monica, CA; The Neurology Center of Southern California (B.M.F.), Carlsbad, CA; Department of Neurology (L.I.G.), University of California, Irvine; UCSF Weill Institute for Neurosciences (A.S.K.), Department of Neurology, University of California, San Francisco; Department of Neurology and Neurological Sciences (N.E.S.), and Stanford Stroke Center, Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurological Surgery (J.W.C.), University of California, Irvine; JCHO Tokyo Shinjuku Medical Center (H.I.), Japan; Department of Neurological Surgery (T.Y.), Okayama University Graduate School of Medicine, Japan; SanBio, Inc. (D.C., B.N., D.B.), Mountain View, CA; Watson & Stonehouse Enterprises LLC (A.H.S.), Pacific Grove, CA; Massachusetts General Hospital and Harvard Medical School (R.M.R.), Boston; Department of Neurosurgery and Stanford Stroke Center (G.K.S.), Stanford University School of Medicine and Stanford Health Care, CA; Biostatistical Consulting Inc. (E.C.P.), Mountain View, CA; and Neurotrauma Rehabilitation Associates LLC (A.H.W.), Littleton, CO.
Background And Objectives: Traumatic brain injury (TBI) is frequently characterized by chronic motor deficits. Therefore, this clinical trial assessed whether intracranial implantation of allogeneic modified mesenchymal stromal (SB623) cells can improve chronic motor deficits after TBI.
Methods: Post hoc analysis of the double-blind, randomized, prospective, surgical sham-controlled, phase 2, STEMTRA clinical trial (June 2016 and March 2019) with 48 weeks of follow-up was conducted.
Neuroscience
August 2024
SanBio Inc. Department of Research - In vitro, USA.
Mesenchymal stromal cells (MSCs) hold therapeutic potential for neurological disorders, but their impact on neuronal activity remains unclear. We investigated the effects of SB623 cells (Notch-1 intracellular domain-transfected MSCs) and parental MSCs on human induced pluripotent stem cell (iPSC)-derived neurons using multi-electrode arrays. SB623 cells significantly increased neuronal activity and oscillation in a dose-dependent manner, surpassing astrocytes in promoting network bursts.
View Article and Find Full Text PDFStem Cell Res Ther
May 2023
Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
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