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Transplantation of Human Brain-Derived Ischemia-Induced Multipotent Stem Cells Ameliorates Neurological Dysfunction in Mice After Stroke.
Nakagomi, Takayuki; Nakano-Doi, Akiko; Kubo, Shuji; Sawano, Toshinori; Kuramoto, Yoji; Yamahara, Kenichi; Matsuyama, Tomohiro; Takagi, Toshinori; Doe, Nobutaka; Yoshimura, Shinichi.
Afiliação
  • Nakagomi T; Institute for Advanced Medical Sciences, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan.
  • Nakano-Doi A; Department of Therapeutic Progress in Brain Diseases, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan.
  • Kubo S; Institute for Advanced Medical Sciences, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan.
  • Sawano T; Department of Therapeutic Progress in Brain Diseases, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan.
  • Kuramoto Y; Institute for Advanced Medical Sciences, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan.
  • Yamahara K; Department of Biomedical Sciences, Ritsumeikan University, Kusatsu, Japan.
  • Matsuyama T; Department of Neurosurgery, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan.
  • Takagi T; Institute for Advanced Medical Sciences, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan.
  • Doe N; Department of Therapeutic Progress in Brain Diseases, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan.
  • Yoshimura S; Department of Neurosurgery, Hyogo Medical University (Nishinomiya Campus), Nishinomiya, Hyogo, Japan.
Stem Cells Transl Med ; 12(6): 400-414, 2023 06 15.
Article em En | MEDLINE | ID: mdl-37221140
ABSTRACT
We recently demonstrated that injury/ischemia-induced multipotent stem cells (iSCs) develop within post-stroke human brains. Because iSCs are stem cells induced under pathological conditions, such as ischemic stroke, the use of human brain-derived iSCs (h-iSCs) may represent a novel therapy for stroke patients. We performed a preclinical study by transplanting h-iSCs transcranially into post-stroke mouse brains 6 weeks after middle cerebral artery occlusion (MCAO). Compared with PBS-treated controls, h-iSC transplantation significantly improved neurological function. To identify the underlying mechanism, green fluorescent protein (GFP)-labeled h-iSCs were transplanted into post-stroke mouse brains. Immunohistochemistry revealed that GFP+ h-iSCs survived around the ischemic areas and some differentiated into mature neuronal cells. To determine the effect on endogenous neural stem/progenitor cells (NSPCs) by h-iSC transplantation, mCherry-labeled h-iSCs were administered to Nestin-GFP transgenic mice which were subjected to MCAO. As a result, many GFP+ NSPCs were observed around the injured sites compared with controls, indicating that mCherry+ h-iSCs activate GFP+ endogenous NSPCs. In support of these findings, coculture studies revealed that the presence of h-iSCs promotes the proliferation of endogenous NSPCs and increases neurogenesis. In addition, coculture experiments indicated neuronal network formation between h-iSC- and NSPC-derived neurons. These results suggest that h-iSCs exert positive effects on neural regeneration through not only neural replacement by grafted cells but also neurogenesis by activated endogenous NSPCs. Thus, h-iSCs have the potential to be a novel source of cell therapy for stroke patients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Isquemia Encefálica / Acidente Vascular Cerebral / Células-Tronco Neurais Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Stem Cells Transl Med Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Isquemia Encefálica / Acidente Vascular Cerebral / Células-Tronco Neurais Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Stem Cells Transl Med Ano de publicação: 2023 Tipo de documento: Article