Human adipose-derived multipotent stromal cells enriched with IL-10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shift

Abstract

Diabetic wounds present a significant challenge in regenerative medicine due to impaired healing, characterized by prolonged inflammation and deficient tissue repair, primarily caused by a skewed pro-inflammatory macrophage phenotype. This study investigates the therapeutic potential of interleukin-10 (IL-10) chemically modified mRNA (modRNA)-enriched human adipose-derived multipotent stromal cells (hADSCs) in a well-established murine model of diabetic wounds. The modRNAs used in this study were chemically modified using N1-methylpseudouridine-5′-triphosphate (m1Ψ) by substituting uridine-5-triphosphate. In vitro experiments demonstrated that IL-10 modRNA-transfected hADSCs effectively modulated macrophage polarization towards an anti-inflammatory phenotype. In vivo experiments with a well-established murine model demonstrated that transplantation of hADSCsmodIL-10 on postoperative day 5 (POD5) significantly improved wound healing outcomes, including accelerated wound closure, enhanced re-epithelialization, promoted M2 polarization, improved collagen deposition, and increased neovascularization. This study concludes that IL-10 modRNA-enriched hADSCs offer a promising therapeutic approach for diabetic wound healing, with the timing of IL-10 administration playing a crucial role in its effectiveness. These cells modulate macrophage polarization and promote tissue repair, demonstrating their potential for improving the management of diabetic wounds.