| RRC ID |
85418
|
| Author |
Nakagomi T, Nakano-Doi A, Kubo S, Sawano T, Kuramoto Y, Yamahara K, Matsuyama T, Takagi T, Doe N, Yoshimura S.
|
| Title |
Transplantation of Human Brain-Derived Ischemia-Induced Multipotent Stem Cells Ameliorates Neurological Dysfunction in Mice After Stroke.
|
| Journal |
Stem Cells Transl Med
|
| 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.
|
| Volume |
12(6)
|
| Pages |
400-414
|
| Published |
2023-6-15
|
| DOI |
10.1093/stcltm/szad031
|
| PII |
7177376
|
| PMID |
37221140
|
| PMC |
PMC10267578
|
| MeSH |
Animals
Brain / pathology
Brain Ischemia* / metabolism
Brain Ischemia* / therapy
Humans
Mice
Mice, Transgenic
Multipotent Stem Cells
Neural Stem Cells*
Neurogenesis / physiology
Stroke* / pathology
Stroke* / therapy
|
| IF |
6.429
|
| Resource |
| Mice |
RBRC06355 |
