Adipose-Derived Stem Cell Conditioned Medium and Wound Healing: A Systematic Review.

Adipose-derived stem cells (ASCs) have been growing in popularity for their potential in wound healing and tissue engineering. Stem cell therapies are limited in application, with the need to maintain cell viability and function as well as safety concerns. It has been increasingly reported that the effects of ASCs are predominantly attributable to the paracrine effects of the secreted factors, which can be collected in conditioned medium (CM). The goal of this systematic review was to investigate the effects on wound healing of CM collected from ASC culture. Original articles relevant to ASC-CM and wound healing (in vitro: dermal fibroblast, epidermal keratinocytes, and their equivalent cell lines; in vivo: full-thickness wound models) were included. The agreement level of selections between two investigators was calculated by the kappa scores. And the information concerning to the publications, CM preparation, and its application and effects was extracted and reported in a systematic way and summarized in tables. In total, 121 publications were initially identified through a search of the PubMed/MEDLINE database with a specific search algorithm, and 36 articles were ultimately included after 2 screenings. Nineteen were in vitro studies that met the search criteria and 17 were in vivo studies with or without in vitro data. In summary, based on the included articles, treatment with ASC-CM, to a large extent, resulted in positive effects on wound healing in vitro and in vivo. Modulation of the culture conditions of ASCs producing the CM, including hypoxic conditions, alternative substrates, medium supplementation, as well as genetic modification of cells, favorably promoted the effects of ASC-CM. Finally, a discussion of the future perspectives and therapeutic potential of ASC-CM, which also addresses the limitations of the field, is presented. A limitation of the evidence is the inconsistency in CM preparation methods among included articles. In conclusion, ASC-CM is a promising novel cell-free therapy for wound healing in regenerative medicine and warrants further exploration. Impact Statement This systematic review researched in vitro and in vivo studies regarding therapeutic effects of adipose-derived stem cell (ASC) conditioned medium (CM) on wound healing, generally indicating favorable effects. ASC-CM can avoid safety concerns accompanying stem cell therapies and reduce the cost of treatment. Modulation in the process of ASC culture and CM preparation may promote its therapeutic potential. The limitation and future perspectives of the field of ASC-CM therapy were also presented. ASC-CM may be useful to its future application for a wide range of clinical targets including inflammatory and ischemic diseases.