Mesenchymal Stem Cell Transplantation Ameliorates Ara-C-Induced Motor Deficits in a Mouse Model of Cerebellar Ataxia

Autor: Narae Park, Chanchal Sharma, Un Ju Jung, Sehwan Kim, Youngpyo Nam, Kyung-Suk Kim, Kyoungho Suk, Ho-Won Lee, Sang Ryong Kim
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Clinical Medicine, Vol 12, Iss 5, p 1756 (2023)
Druh dokumentu: article
ISSN: 12051756
2077-0383
DOI: 10.3390/jcm12051756
Popis: This study investigated the therapeutic effects of transplanting human mesenchymal stem cells (hMSCs) into wild-type mice that were intraperitoneally administered cytosine arabinoside (Ara-C) to develop cerebellar ataxia (CA) during the first three postnatal days. hMSCs were intrathecally injected into 10-week-old mice once or thrice at 4-week intervals. Compared to the nontreated mice, the hMSC-treated mice showed improved motor and balance coordination, as measured using the rotarod, open-field, and ataxic scoring assessments, and increased protein levels in Purkinje and cerebellar granule cells, as measured using calbindin and NeuN protein markers. Multiple hMSC injections preserved Ara-C-induced cerebellar neuronal loss and improved cerebellar weight. Furthermore, the hMSC implantation significantly elevated the levels of neurotrophic factors, including brain-derived and glial cell line-derived neurotrophic factors, and suppressed TNF-α-, IL-1β-, and iNOS-mediated proinflammatory responses. Collectively, our results demonstrate that hMSCs exhibit therapeutic potential for Ara-C-induced CA by protecting neurons through the stimulation of neurotrophic factors and inhibition of cerebellar inflammatory responses, which can improve motor behavior and alleviate ataxia-related neuropathology. In summary, this study suggests that hMSC administration, particularly multiple treatments, can effectively treat ataxia-related symptoms with cerebellar toxicity.
Databáze: Directory of Open Access Journals
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