The skin regeneration potential of a pro-angiogenic secretome from human skin-derived multipotent stromal cells

Abstract

Multipotent stromal cells stimulate skin regeneration after acute or chronic injuries. However, many stem cell therapy protocols are limited by the elevated number of cells required and poor cell survival after transplantation. Considering that the beneficial effects of multipotent stromal cells on wound healing are typically mediated by paracrine mechanisms, we examined whether the conditioned medium from skin-derived multipotent stromal cells would be beneficial for restoring the skin structure of mice after wounding. A proteomic characterization of skin-derived multipotent stromal cell-conditioned medium was performed, and the angiogenic function of this secretome was investigated in vitro using an endothelial cell tube formation assay. We then applied the skin-derived multipotent stromal cell-conditioned medium directly to full-thickness excisional wounds or embedded it into carrageenan or poly(vinyl alcohol) hydrogels to monitor tissue regeneration in mice. Biological processes related to wound healing and angiogenesis were highlighted by the analysis of the skin-derived multipotent stromal cell secretome, and a pro-angiogenic capacity for promoting tubule-like structures was first confirmed in vitro. Skin wounds treated with skin-derived multipotent stromal cell-conditioned medium also displayed increased angiogenesis, independently of the association of the conditioned medium with hydrogels. However, improvements in wound closure and epidermis or decreased inflammatory cell presence were not observed. Hence, the use of the secretome obtained from human skin-derived multipotent stromal cells may be a potential strategy to aid the natural skin repair of full-thickness lesions mainly based on its pro-angiogenic properties.

Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration

“…[ 233 ] Another study observed that MSC‐CM embedded in a natural seaweed‐derived material, Carrageenan (CG), or a synthetic poly(vinyl alcohol) (PVA) polymer, enhanced angiogenesis in vitro and in vivo, although MSC‐CM without a biomaterial carrier showed no difference from untreated controls. [ 234 ] MSC‐EVs delivered in a chitosan/silk hydrogel [ 235 ] and in a self‐healing, anti‐bacterial polypeptide hydrogel [ 58 ] promoted cutaneous wound healing in diabetic rat models. One study demonstrated that an EV‐laden hydrogel reduced myofibroblast accumulation and scar formation in skin wounds, and showed that EV‐mediated inhibition of myofibroblast differentiation in vitro was facilitated by RNA and not protein EV cargo.…”

Prevention of excessive scar formation using nanofibrous meshes made of biodegradable elastomer poly(3-hydroxybutyrate-co-3-hydroxyvalerate)

“…The fibrous structure not only supports cell attachment and migration, but also induces orderly ECM deposition. Although PHBV-based scaffolds cannot completely reconstruct the skin tissues and prevent scar formation due to a lack of biochemical cues, 55 we believe PHBV nanofibrous meshes with a 3HV content of 30-60 mol% are promising materials for wound healing applications due to their superior mechanical offloading, mechanomodulation, biocompatibility, and slow degradation.…”

Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers

“…The process of wound healing includes several overlapping stages: for example, hemostasis, inflammation, proliferation, as well as re-epithelialization and remodeling. 40,41 The aggregation and activation of inflammatory cells is a critical step in the transition from the inflammatory phase to the repair phase. But the excessive inflammatory reaction will lead to a chronic inflammatory microenvironment and delayed wound healing.…”