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. 2022 Aug 6;7:272. doi: 10.1038/s41392-022-01134-4

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — Adipose tissue-derived mesenchymal stem cells (AT-MSCs) and the nature of their tissue of origin support their use in therapeutic applications. a Adipose tissue is considered an endocrine organ, supporting and regulating various functions, including appetite regulation, immune regulation, sex hormone and glucocorticoid metabolism, energy production, the orchestration of reproduction, the control of vascularization, and blood flow, the regulation of coagulation, and angiogenesis and skin regeneration. b In terms of metabolic disorders, such as type 2 diabetes mellitus (T2DM), as adipose tissue is directly involved in the metabolism of glucose and lipids and the regulation of appetite, the detrimental effects of T2DM also alter the functions of AT-MSCs, which in turn, hampers their therapeutic effects. Hence, the use of autologous AT-MSCs is not recommended for the treatment of metabolic disorders, including T2DM, suggesting that allogeneic AT-MSCs from healthy donors could be a better alternative approach. c AT-MSCs are suitable for the treatment of reproductive disorders due to their unique ability to mobilize and home to the thecal layer of the injured ovary, enhance the regeneration and maturation of thecal cells, increase the structure and function of damaged ovaries via exosome-activated SMAD, decrease oxidative stress and autophagy, and increase the proliferation of granulosa cells via PI3K/AKT pathways. These functions are regulated specifically by growth hormones produced by AT-MSCs in response to the surrounding environment, including HGF, TGF-β, IGF-1, and EGF. d AT-MSCs are also good candidates for skin healing and regeneration as their growth factors strongly support neovascularization and angiogenesis by reducing PLL4, increase anti-apoptosis via the activation of PI3K/AKT pathways, regulate inflammation by downregulating NADPH oxidase isoform 1, and increase immunoregulation through the inhibition of NF-κB activation. The figure was created with BioRender.com