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Therapeutic Effect of Schwann Cell-Like Cells Differentiated from Human Tonsil-Derived Mesenchymal Stem Cells on Diabetic Neuropathy in db/db Mice

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Diabetic neuropathy (DN) is the most common complication of diabetes, and approximately 50% of patients with this disease suffer from peripheral neuropathy. Nerve fiber loss in DN occurs due to myelin defects and is characterized by symptoms of impaired nerve function. Schwann cells (SCs) are the main support cells of the peripheral nervous system and play important roles in several pathways contributing to the pathogenesis and development of DN. We previously reported that human tonsil-derived mesenchymal stem cells differentiated into SCs (TMSC-SCs), named neuronal regeneration-promoting cells (NRPCs), which cells promoted nerve regeneration in animal models with peripheral nerve injury or hereditary peripheral neuropathy.

Methods:

In this study, NRPCs were injected into the thigh muscles of BKS-db/db mice, a commonly used type 2 diabetes model, and monitored for 26 weeks. Von Frey test, sensory nerve conduction study, and staining of sural nerve, hind foot pad, dorsal root ganglia (DRG) were performed after NRPCs treatment.

Results:

Von Frey test results showed that the NRPC treatment group (NRPC group) showed faster responses to less force than the vehicle group. Additionally, remyelination of sural nerve fibers also increased in the NRPC group. After NRPCs treatment, an improvement in response to external stimuli and pain sensation was expected through increased expression of PGP9.5 in the sole and TRPV1 in the DRG.

Conclusion:

The NRPCs treatment may alleviate DN through the remyelination and the recovery of sensory neurons, could provide a better life for patients suffering from complications of this disease.

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Data availability statement

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This study was supported by a Korean Fund for Regenerative Medicine (KFRM) grant, funded by the Korea government (the Ministry of Science and ICT, the Ministry of Health & Welfare) (22C0627L1-11), a Basic Science Research Program through the NRF funded by the Ministry of Education (2022R1I1A01064295) and the RP-Grant 2023 of Ewha Womans University.

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Author notes

  1. Yoonji Yum and Saeyoung Park have contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, College of Medicine, Ewha Womans University, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul, 07804, Republic of Korea

    Yoonji Yum, Saeyoung Park, Yu Hwa Nam, Juhee Yoon, Hyeryung Song & Sung-Chul Jung

  2. Graduate Program in System Health Science and Engineering, Ewha Womans University, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul, 07804, Republic of Korea

    Sung-Chul Jung

  3. Cellatoz Therapeutics Lnc., 17, Pangyo-ro 228beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13487, Republic of Korea

    Ho Jin Kim & Jaeseung Lim

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Contributions

S-CJ conceived and designed the study; YY, SP, YHN, JY and SH performed experiments; YY, SP and S-CJ analyzed the data; HJK and JL resources; YY, SP and S-CJ wrote the paper All authors have read and agreed to the final version of the manuscript.

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Correspondence to Sung-Chul Jung.

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Conflict of interest

H.J.K. and J.L. are employees of Cellatoz Therapeutics, Inc.; S.-C.J. is a scientific advisory board member of Cellatoz Therapeutics, Inc.; The other authors declare no conflict of interest.

Ethical statement

The study protocol was approved by the Ewha Womans University Medical Center (EWUMC) institutional review board (IRB number: EUMC-2021-09-036). All the experimental procedures were reviewed and approved by the ethics committee for animal research at Ewha Woman’s University (EWHA MEDIACUC 22-005-3). Informed Consent Statement: Informed written consent was obtained from all the patients participating in the study.

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Yum, Y., Park, S., Nam, Y.H. et al. Therapeutic Effect of Schwann Cell-Like Cells Differentiated from Human Tonsil-Derived Mesenchymal Stem Cells on Diabetic Neuropathy in db/db Mice. Tissue Eng Regen Med (2024). https://doi.org/10.1007/s13770-024-00638-0

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