Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Enhanced effects of Wharton’s jelly–derived MSC secretome and microbial exopolysaccharide on cellular responses and tissue repair in diabetic wound healing

Articles in Press

Document Type : Original Article

Authors
Hossein Rostami 1
Seyed Mohamad Amin Haramshahi 2, 3
Nasim Vousooghi 1
Somayeh Shamlou 1
Zeinab Shahmahmoudi 2, 3
Peiman Brouki Milan 2, 3
Javad Verdi 1
1 Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
3 Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
10.22038/ijbms.2026.95558.20615
Abstract
Objective(s): Diabetic wounds are characterized by impaired healing and chronic inflammation. This study evaluated a combination therapy using an exopolysaccharide derived from Rhodotorula mucilaginosa sp. GUMS16 (EPS-GUMS16) and Wharton’s jelly-derived mesenchymal stem cell-conditioned medium (WCM) to accelerate wound repair.
Materials and Methods: Human foreskin fibroblasts (HFFs) and human umbilical vein endothelial cells (HUVECs) were treated with an optimized concentration of the WCM/EPS-GUMS16 (WCM/EPS) combination. In vitro assays, including MTT and scratch wound assays, were conducted to assess cell proliferation and migration. In vivo, full-thickness wounds in diabetic rats were treated with WCM/EPS via subcutaneous injection and topical application. Wound healing was monitored by measuring the reduction in wound surface area, and histopathological evaluation was performed using hematoxylin and eosin (H&E) and Masson’s trichrome (MT) staining.
Results: In vitro assessments showed that WCM/EPS enhanced fibroblast proliferation and migration (P<0.05) and significantly upregulated CDK-4 expression (P<0.05). In vivo, treated wounds exhibited increased epidermal thickness and altered blood vessel density compared with controls. Semi-quantitative histopathological analysis further revealed enhanced re-epithelialization, more organized granulation tissue, and reduced inflammation and edema. These findings indicate that WCM/EPS effectively modulates inflammation and angiogenesis, thereby promoting tissue regeneration in diabetic wounds.
Conclusion: Overall, this combination is a promising strategy for improving diabetic wound healing and highlights the potential of integrating microbial exopolysaccharides with stem cell-derived conditioned media in regenerative therapies.
Keywords
Diabetes mellitus
Wound healing
Mesenchymal stem cells
Secretome
Fibroblasts
Endothelial cells
Exopolysaccharide
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 31 August 2026