Innovative diabetes mellitus treatment strategies: Mesenchymal stem cell-based therapy and its impact on pro- and anti-inflammatory cytokines modulation

Amin Ullah; Yutao Wu; Rajeev K. Singla; Weidong Tian; Bairong Shen

doi:10.1016/j.jpha.2025.101497

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Amin Ullah, Yutao Wu, Rajeev K. Singla, Weidong Tian, Bairong Shen. Innovative diabetes mellitus treatment strategies: Mesenchymal stem cell-based therapy and its impact on pro- and anti-inflammatory cytokines modulation[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101497

Citation:

Amin Ullah, Yutao Wu, Rajeev K. Singla, Weidong Tian, Bairong Shen. Innovative diabetes mellitus treatment strategies: Mesenchymal stem cell-based therapy and its impact on pro- and anti-inflammatory cytokines modulation[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101497

Citation:

Amin Ullah, Yutao Wu, Rajeev K. Singla, Weidong Tian, Bairong Shen. Innovative diabetes mellitus treatment strategies: Mesenchymal stem cell-based therapy and its impact on pro- and anti-inflammatory cytokines modulation[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101497

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Innovative diabetes mellitus treatment strategies: Mesenchymal stem cell-based therapy and its impact on pro- and anti-inflammatory cytokines modulation

doi: 10.1016/j.jpha.2025.101497

a. Department of Endocrinology and Metabolism, Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China;
b. Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China;
c. School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, 144411, India

Funds:

This work was supported by the National Natural Science Foundation of China (Grant No.: 32270690) and the Sichuan Science and Technology Program, China (Grant Nos.: 2025YFHZ0213 and 2024YFHZ0205). Additional financial support was provided by West China Hospital, Sichuan University, China. Figs. 1−6 and the graphical abstract were created with BioRender.com. We thank LetPub (www.letpub.com.cn) and Caproslaxy Media (https://www.caproslaxymedia.com/) for linguistic assistance during the preparation of this manuscript.

Received Date: May 01, 2025
Accepted Date: Nov. 21, 2025
Rev Recd Date: Nov. 14, 2025
Available Online: Nov. 25, 2025

Abstract

Abstract

Diabetes mellitus (DM) is a metabolic condition defined by chronic hyperglycemia with serious complications, including retinopathy, neuropathy, cardiopathy, and nephropathy. DM often accelerates inflammatory responses, which traditional treatments frequently fail to control. Chronic inflammation, with an imbalance between pro-inflammatory and anti-inflammatory cytokines, causes pancreatic β-cell failure and tissue damage. Mesenchymal stem cells (MSCs) are emerging as a promising therapy because of their capacity to control immune responses and stimulate tissue repair. Interleukin-1β (IL-1β), IL-17, IL-6, and tumor necrosis factor-α (TNF-α) have crucial roles in the diabetes-associated inflammatory environment. MSC therapies reduce levels of pro-inflammatory cytokines and increase levels of anti-inflammatory cytokines, such as IL-10, IL-4, IL-13, and transforming growth factor-β (TGF-β), reducing inflammation and promoting wound healing. Moreover, the dual functions in inflammation and tissue repair of key cytokines, including TGF-β, IL-6, IL-2, IL-33, and IL-8, provide both challenges and opportunities in MSC therapy. This review explores innovative MSC-based therapies for treating DM, focusing on their modulation of pro- and anti-inflammatory cytokines. MSCs may help reduce diabetic complications by restoring the cytokine balance, increasing insulin sensitivity, and protecting organs. However, the unique source of MSCs and the complex cytokine milieu in DM warrant additional research to improve treatment strategies and ensure long-term safety and efficacy. By highlighting the potential of MSCs to improve DM treatment and enhance patient outcomes, this review attempts to provide a thorough understanding of the molecular mechanisms by which MSCs regulate cytokine activity.
- Diabetes mellitus,
- Mesenchymal stem cells,
- Pro- and anti-inflammatory cytokines,
- Immune modulation,
- Tissue repair

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References(150)

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