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Human amniotic epithelial stem cell-derived dopaminergic neuron-like cells ameliorate motor dysfunction in a rat model of Parkinson's disease.
- Source :
-
Life Sciences . Aug2024, Vol. 351, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
-
Abstract
- Parkinson's disease (PD) remains a substantial clinical challenge due to the progressive loss of midbrain dopaminergic (DA) neurons in nigrostriatal pathway. In this study, human amniotic epithelial stem cells (hAESCs)-derived dopaminergic neuron-like cells (hAESCs-DNLCs) were generated, with the aim of providing new therapeutic approach to PD. hAESCs, which were isolated from discarded placentas, were induced to differentiate into hAESCs-DNLCs by following a "two stages" induction protocol. The differentiation efficiency was assessed by quantitative real-time PCR (qRT-PCR), immunocytochemistry (ICC), and ELISA. Immunogenicity, cell viability and tumorigenicity of hAESCs-DNLC were analyzed before in vivo experiments. Subsequently, hAESCs-DNLCs were transplanted into PD rats, behavioral tests were monitored after graft, and the regeneration of DA neurons was detected by immunohistochemistry (IHC). Furthermore, to trace hAESCs-DNLCs in vivo , cells were pre-labeled with PKH67 green fluorescence. hAESCs were positive for pluripotent markers and highly expressed neural stem cells (NSCs) markers. Based on this, we established an induction method reliably generates hAESCs-DNLCs, which was evidenced by epithelium-to-neuron morphological changes, elevated expressions of neuronal and DA neuronal markers, and increased secretion of dopamine. Moreover, hAESCs-DNLCs maintained high cell viability, no tumorigenicity and low immunogenicity, suggesting hAESCs-DNLCs an attractive implant for PD therapy. Transplantation of hAESCs-DNLCs into PD rats significantly ameliorated motor disorders, as well as enhanced the reinnervation of TH+ DA neurons in nigrostriatal pathway. Our study has demonstrated evident therapeutic effects of hAESCs-DNLCs, and provides a safe and promising solution for PD. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00243205
- Volume :
- 351
- Database :
- Academic Search Index
- Journal :
- Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 178148932
- Full Text :
- https://doi.org/10.1016/j.lfs.2024.122816