Human Nasal Inferior Turbinate-Derived Neural Stem Cells Improve the Niche of Substantia Nigra Par Compacta in a Parkinson's Disease Model by Modulating Hippo Signaling.

Autor: Choi J; Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.; Postech-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Park SW; Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.; Postech-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Lee H; Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.; Postech-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Kim DH; Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea., Kim SW; Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea. kswent@catholic.ac.kr.; Postech-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. kswent@catholic.ac.kr.
Jazyk: angličtina
Zdroj: Tissue engineering and regenerative medicine [Tissue Eng Regen Med] 2024 Jul; Vol. 21 (5), pp. 737-748. Date of Electronic Publication: 2024 Apr 10.
DOI: 10.1007/s13770-024-00635-3
Abstrakt: Background: Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, following Alzheimer's disease. The onset of PD is characterized by the loss of dopaminergic neurons in the substantia nigra. Stem cell therapy has great potential for the treatment of neurodegenerative diseases, and human nasal turbinate-derived stem cells (hNTSCs) have been found to share some characteristics with mesenchymal stem cells. Although the Hippo signaling pathway was originally thought to regulate cell size in organs, recent studies have shown that it can also control inflammation in neural cells.
Methods: Dopaminergic neuron-like cells were differentiated from SH-SY5Y cells (DA-Like cells) and treated with 1-Methyl-4-phenylpyridinium iodide to stimulate Reactive oxidative species (ROS) production. A transwell assay was conducted to validate the effect of hNTSCs on the Hippo pathway. We generated an MPTP-induced PD mouse model and transplanted hNTSCs into the substantia nigra of PD mice via stereotaxic surgery. After five weeks of behavioral testing, the brain samples were validated by immunoblotting and immunostaining to confirm the niche control of hNTSCs.
Results: In-vitro experiments showed that hNTSCs significantly increased cell survival and exerted anti-inflammatory effects by controlling ROS-mediated ER stress and hippocampal signaling pathway factors. Similarly, the in-vivo experiments demonstrated an increase in anti-inflammatory effects and cell survival rate. After transplantation of hNTSCs, the PD mouse model showed improved mobility and relief from PD symptoms.
Conclusion: hNTSCs improved the survival rate of dopaminergic neurons by manipulating the hippocampal pathway through Yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding motif (TAZ) by reducing inflammatory cytokines. In this study, we found that controlling the niche of hNTSCs had a therapeutic effect on PD lesions.
(© 2024. The Author(s).)
Databáze: MEDLINE
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