Synergistic effect of Wharton's jelly-derived mesenchymal stem cells and insulin on Schwann cell proliferation in Charcot-Marie-Tooth disease type 1A treatment
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...
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Elsevier
2024-12-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996124003279 |
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| author | Shin Ji Oh Hyeongseop Kim Sang Eon Park Jeong Hee Kim Yong Jun Kim Suk-joo Choi Soo-young Oh Hong Bae Jeon Jong Wook Chang |
| author_facet | Shin Ji Oh Hyeongseop Kim Sang Eon Park Jeong Hee Kim Yong Jun Kim Suk-joo Choi Soo-young Oh Hong Bae Jeon Jong Wook Chang |
| author_sort | Shin Ji Oh |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0c8322bbe1cc49f499deea4f40ade682 |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-0c8322bbe1cc49f499deea4f40ade6822024-12-14T06:29:52ZengElsevierNeurobiology of Disease1095-953X2024-12-01203106725Synergistic effect of Wharton's jelly-derived mesenchymal stem cells and insulin on Schwann cell proliferation in Charcot-Marie-Tooth disease type 1A treatmentShin Ji Oh0Hyeongseop Kim1Sang Eon Park2Jeong Hee Kim3Yong Jun Kim4Suk-joo Choi5Soo-young Oh6Hong Bae Jeon7Jong Wook Chang8Cell & 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 KoreaCell & Gene Therapy Research Institute, ENCell Co. Ltd., Seoul 06072, Republic of Korea; Cell and Gene Therapy Institute, Samsung Medical Center, Seoul 06351, Republic of KoreaCell & Gene Therapy Research Institute, ENCell Co. Ltd., Seoul 06072, Republic of Korea; Cell and Gene Therapy Institute, Samsung Medical Center, Seoul 06351, Republic of KoreaDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment 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 KoreaDepartment of Obstetrics and Gynecology, Samsung Medical Center, Seoul 06351, Republic of KoreaDepartment of Obstetrics and Gynecology, Samsung Medical Center, Seoul 06351, Republic of KoreaCell & Gene Therapy Research Institute, ENCell Co. Ltd., Seoul 06072, Republic of Korea; Correspondence to: Hong Bae Jeon, Cell & Gene Research Therapy Institute, ENCell Co. Ltd., 701 Yeongdong-daero, Gangnam-gu, Seoul 06072, Republic of Korea.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; Correspondence to: Jong Wook Chang, Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea.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.http://www.sciencedirect.com/science/article/pii/S0969996124003279Charcot-Marie-Tooth disease type 1AWharton's jelly-derived mesenchymal stem cellMesenchymal stem cellInsulinCombination therapyRegenerative medicine |
| spellingShingle | Shin Ji Oh Hyeongseop Kim Sang Eon Park Jeong Hee Kim Yong Jun Kim Suk-joo Choi Soo-young Oh Hong Bae Jeon Jong Wook Chang Synergistic effect of Wharton's jelly-derived mesenchymal stem cells and insulin on Schwann cell proliferation in Charcot-Marie-Tooth disease type 1A treatment Neurobiology of Disease Charcot-Marie-Tooth disease type 1A Wharton's jelly-derived mesenchymal stem cell Mesenchymal stem cell Insulin Combination therapy Regenerative medicine |
| title | Synergistic effect of Wharton's jelly-derived mesenchymal stem cells and insulin on Schwann cell proliferation in Charcot-Marie-Tooth disease type 1A treatment |
| title_full | Synergistic effect of Wharton's jelly-derived mesenchymal stem cells and insulin on Schwann cell proliferation in Charcot-Marie-Tooth disease type 1A treatment |
| title_fullStr | Synergistic effect of Wharton's jelly-derived mesenchymal stem cells and insulin on Schwann cell proliferation in Charcot-Marie-Tooth disease type 1A treatment |
| title_full_unstemmed | Synergistic effect of Wharton's jelly-derived mesenchymal stem cells and insulin on Schwann cell proliferation in Charcot-Marie-Tooth disease type 1A treatment |
| title_short | Synergistic effect of Wharton's jelly-derived mesenchymal stem cells and insulin on Schwann cell proliferation in Charcot-Marie-Tooth disease type 1A treatment |
| title_sort | synergistic effect of wharton s jelly derived mesenchymal stem cells and insulin on schwann cell proliferation in charcot marie tooth disease type 1a treatment |
| topic | Charcot-Marie-Tooth disease type 1A Wharton's jelly-derived mesenchymal stem cell Mesenchymal stem cell Insulin Combination therapy Regenerative medicine |
| url | http://www.sciencedirect.com/science/article/pii/S0969996124003279 |
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