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Mesenchymal Stem Cell-Based Therapy for Diabetes Mellitus: Enhancement Strategies and Future Perspectives

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Abstract

Diabetes mellitus (DM), a chronic disorder of carbohydrate metabolism, is characterized by the unbridled hyperglycemia resulted from the impaired ability of the body to either produce or respond to insulin. As a cell-based regenerative therapy, mesenchymal stem cells (MSCs) hold immense potency for curing DM duo to their easy isolation, multi-differentiation potential, and immunomodulatory property. However, despite the promising efficacy in pre-clinical animal models, naive MSC administration fails to exhibit clinically satisfactory therapeutic outcomes, which varies greatly among individuals with DM. Recently, numbers of innovative strategies have been applied to improve MSC-based therapy. Preconditioning, genetic modification, combination therapy and exosome application are representative strategies to maximize the therapeutic benefits of MSCs. Therefore, in this review, we summarize recent advancements in mechanistic studies of MSCs-based treatment for DM, and mainly focus on the novel approaches aiming to improve the anti-diabetic potentials of naive MSCs. Additionally, the potential directions of MSCs-based therapy for DM are also proposed at a glance.

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Data Availability

The literatures in this study are available from the corresponding authors on reasonable request.

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Acknowledgments

This work was supported by grants from National Key Research and Development Program of China (Grant No. 2017YFA0103902 & 2019YFA0111400), the National Natural Science Foundation of China (Grant No. 31771283), Innovative Research Team of High-level Local Universities in Shanghai (Grant No. SSMU-ZDCX20180700) and a Key Laboratory Program of the Education Commission of Shanghai Municipality (Grant No. ZDSYS14005).

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Author notes

  1. Haisen Li and Hao Zhu contributed equally to this work.

Authors and Affiliations

  1. Department of Plastic and Reconstructive Surgery, Shanghai Institute of Precision Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China

    Haisen Li, Zhifeng Wang & Chao Zhang

  2. Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China

    Haisen Li, Zhifeng Wang & Chao Zhang

  3. Sinoneural Cell Engineering Group Holdings Co., Ltd., Shanghai 201100, China

    Haisen Li, Hao Zhu & Zhifeng Wang

  4. Xinxiang First People’s Hospital, Xinxiang 453000, China

    Ting Ge

Authors
  1. Haisen Li
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  2. Hao Zhu
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  3. Ting Ge
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  4. Zhifeng Wang
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  5. Chao Zhang
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Contributions

HS.L. performed the literature search, devised the conceptual ideas, and wrote the manuscript. H.Z. performed the literature search, and wrote the manuscript. T.G. performed the literature search. ZF.W. devised the conceptual ideas, wrote the manuscript, and critically revised the manuscript. C.Z. initiated the study, revised the manuscript, and supervised the project.

Corresponding authors

Correspondence to Zhifeng Wang or Chao Zhang.

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Li, H., Zhu, H., Ge, T. et al. Mesenchymal Stem Cell-Based Therapy for Diabetes Mellitus: Enhancement Strategies and Future Perspectives. Stem Cell Rev and Rep 17, 1552–1569 (2021). https://doi.org/10.1007/s12015-021-10139-5

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