Multiple therapeutic effects of human neural stem cells derived from induced pluripotent stem cells in a rat model of post-traumatic syringomyelia.
Autor: | Xu T; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, BioClinicum J9:20, Karolinska Institutet, Stockholm, S17164, Sweden. Electronic address: 18243065861@163.com., Li X; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, BioClinicum J9:20, Karolinska Institutet, Stockholm, S17164, Sweden., Guo Y; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, BioClinicum J9:20, Karolinska Institutet, Stockholm, S17164, Sweden., Uhlin E; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden., Holmberg L; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, BioClinicum J9:20, Karolinska Institutet, Stockholm, S17164, Sweden., Mitra S; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden., Winn D; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden., Falk A; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden., Sundström E; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, BioClinicum J9:20, Karolinska Institutet, Stockholm, S17164, Sweden. |
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Jazyk: | angličtina |
Zdroj: | EBioMedicine [EBioMedicine] 2022 Mar; Vol. 77, pp. 103882. Date of Electronic Publication: 2022 Feb 16. |
DOI: | 10.1016/j.ebiom.2022.103882 |
Abstrakt: | Background: Post-traumatic syringomyelia (PTS) affects patients with chronic spinal cord injury (SCI) and is characterized by progressive deterioration of neurological symptoms. To improve surgical treatment, we studied the therapeutic effects of neuroepithelial-like stem cells (NESCs) derived from induced pluripotent stem cells (iPSCs) in a rat model of PTS. To facilitate clinical translation, we studied NESCs derived from Good Manufacturing Practice (GMP)-compliant iPSCs. Methods: Human GMP-compliant iPSCs were used to derive NESCs. Cryo-preserved NESCs were used off-the-shelf for intraspinal implantation to PTS rats 1 or 10 weeks post-injury, and rats were sacrificed 10 weeks later. In vivo cyst volumes were measured with micro-MRI. Phenotypes of differentiated NESCs and host responses were analyzed by immunohistochemistry. Findings: Off-the-shelf NESCs transplanted to PTS rats 10 weeks post-injury reduced cyst volume. The grafted NESCs differentiated mainly into glial cells. Importantly, NESCs also stimulated tissue repair. They reduced the density of glial scars and neurite-inhibiting chondroitin sulfate proteoglycan 4 (CSPG4), stimulated host oligodendrocyte precursor cells to migrate and proliferate, reduced active microglia/macrophages, and promoted axonal regrowth after subacute as well as chronic transplantation. Interpretation: Significant neural repair promoted by NESCs demonstrated that human NESCs could be used as a complement to standard surgery in PTS. We envisage that future PTS patients transplanted with NESCs will benefit both from eliminating the symptoms of PTS, as well as a long-term improvement of the neurological symptoms of SCI. Funding: This work was supported by Vinnova (2016-04134), Karolinska Institutet StratRegen, and the Chinese Scholarship Council. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.) |
Databáze: | MEDLINE |
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