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

OBJECTIVES

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.