ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Stem Cell Research
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1659444
This article is part of the Research TopicExternal Factors Influencing Stem Cells’ Pluripotency, Senescence, and DifferentiationView all 9 articles
Mesenchymal stem cell-conditioned medium accelerates type 2 diabetic wound healing by targeting TNF and chemokine signaling
Provisionally accepted
- 1Fujian Provincial Hospital, Fuzhou, China
- 2The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
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Introduction: Given the crucial role of paracrine signaling in the therapeutic function of adipose tissue-derived mesenchymal stem cells (ADSCs) for skin wound repair, this study aimed to evaluate the efficacy of ADSC-conditioned medium (ACM) in enhancing type 2 diabetic (T2D) wound healing. Methods: The effect of ACM on human umbilical vein endothelial cells (HUVEC) viability and angiogenesis was firstly evaluated by CCK 8 assay and q-PCR analysis, respectively. Next, a T2D rat model was induced by the combination of high fat diet and streptozotocin. Following by the establishment of full-thickness skin defects in T2D rats, ACM or serum free cultured medium was daily injected around the wound edge sfor 7 days. Afterwards, the skin wound healing rate was analyzed, and the skin tissues were assessed by histopathological examination. The mRNA levels of TNF-α, IL-1β, IL-6, and COX-2, as well as IL-12 and IFN-γ were evaluated by q-PCR analysis. Additionally, the transcriptome sequencing and immunohistochemistry were used to reveal the potential mechanism of ACM for T2D skin wound healing. Results: ACM significantly enhanced HUVEC proliferation and angiogenesis while upregulating EGF, bFGF, VEGF, and KDR expression. In T2D rats, ACM accelerated wound closure and suppressed pro-inflammatory mediators (TNF-α, IL-1β, IL-6, COX-2, IL-12, IFN-γ). Notably, transcriptome analysis revealed ACM-mediated downregulation of TNF and chemokine signaling pathways. Discussion: ACM promotes diabetic wound healing through dual mechanisms: (1) stimulating vascularization via growth factor induction and (2) modulating the inflammatory microenvironment by inhibiting TNF/chemokine cascades. These findings position ACM as a promising cell-free therapy for impaired wound healing in diabetes.
Keywords: Adipose tissue-derived mesenchymal stem cells, conditioned medium, type 2 diabetes, skin wound, And regeneration
Received: 07 Jul 2025; Accepted: 02 Sep 2025.
Copyright: © 2025 Huang, Lin, Liu, Lin, Liao and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Naishun Liao, The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
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