Synergistic effect of Wharton's jelly-derived mesenchymal stem cells and insulin on Schwann cell proliferation in Charcot-Marie-Tooth disease type 1A treatment.

Autor: Oh SJ; Cell & Gene Therapy Research Institute, ENCell Co. Ltd., Seoul 06072, Republic of Korea; Cell and Gene Therapy Institute, Samsung Medical Center, Seoul 06351, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea., Kim H; Cell & Gene Therapy Research Institute, ENCell Co. Ltd., Seoul 06072, Republic of Korea; Cell and Gene Therapy Institute, Samsung Medical Center, Seoul 06351, Republic of Korea., Park SE; Cell & Gene Therapy Research Institute, ENCell Co. Ltd., Seoul 06072, Republic of Korea; Cell and Gene Therapy Institute, Samsung Medical Center, Seoul 06351, Republic of Korea., Kim JH; Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea., Kim YJ; Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; KHU-KIST Department of Converging Science and Technology, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea., Choi SJ; Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul 06351, Republic of Korea., Oh SY; Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul 06351, Republic of Korea., Jeon HB; Cell & Gene Therapy Research Institute, ENCell Co. Ltd., Seoul 06072, Republic of Korea. Electronic address: jhb@encellinc.com., Chang JW; Cell & Gene Therapy Research Institute, ENCell Co. Ltd., Seoul 06072, Republic of Korea; Cell and Gene Therapy Institute, Samsung Medical Center, Seoul 06351, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea. Electronic address: changjw@skku.edu.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2024 Dec; Vol. 203, pp. 106725. Date of Electronic Publication: 2024 Nov 12.
DOI: 10.1016/j.nbd.2024.106725
Abstrakt: Charcot-Marie-Tooth disease type 1A (CMT1A) is a demyelinating disease caused by PMP22 duplication and an exceedingly rare hereditary peripheral neuropathy, with an incidence of 1 in 2500. Currently, no cure exists for CMT1A; however, various therapeutic approaches are under development. Considering the known therapeutic effects of mesenchymal stem cells (MSCs) and the relation of blood sugar levels with nerve damage in CMT, this study aimed to confirm the therapeutic effects of MSCs and insulin on CMT, using both in-vitro and in-vivo models. CMT1A in-vitro models were exposed to Wharton's jelly-derived MSCs (WJ-MSCs) or insulin, and the resulting proliferation changes were measured. CMT1A mice were treated with WJ-MSCs or insulin, and their phenotypic changes were observed. We observed improvements in myelination of Schwann cells in vitro and motor function in vivo. Insulin also showed therapeutic efficacy by promoting Schwann cell proliferation. Furthermore, combination therapy using insulin and WJ-MSCs was more effective than WJ-MSCs or insulin alone. Insulin promoted the proliferation of Schwann cells and WJ-MSCs through activation of the ATK and PI3K-MAPK signaling pathways. Overall, this study is the first to confirm the therapeutic efficacy of WJ-MSCs and insulin in CMT1A, and their synergistic effect without causing insulin resistance.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shin Ji Oh, Sang Eon Park, Hong Bae Jeon, and Jong Wook Chang has patent #21772334.5 pending to ENCell Co. Ltd. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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