GMP manufacturing of umbilical cord blood mesenchymal stem cell-released exosomes and verification of wound healing efficacy.

Rationale: Drug development research using exosomes is being actively conducted worldwide. However, clear management standards and verification systems for the use of exosomes as drugs are still being developed. In this study, the effectiveness of exosomes as drug candidates was verified after production in accordance with the guidelines for donor suitability, cell bank construction of cell therapy drugs, and quality control of extracellular vesicles published by the Korean Ministry of Food and Drug Safety (KMFDS). Methods: Basic characteristics were identified using umbilical cord blood mesenchymal stem cells (UCBMSCs)-released exosomes produced in accordance with the three guidelines, and internal component analysis of proteins, lipids, and nucleic acids was performed. In addition, various types of in vitro and in vivo experiments confirmed the skin tissue regeneration efficacy of exosomes. Results: In addition, treatment of two types of skin cells (dermal fibroblast and keratinocyte) with exosomes resulted in a statistically significant increase in the proliferation and migration of skin cells and inhibition of the secretion of pro-inflammatory substances in an inflammatory environment. In an animal model of wound injury, exosome treatment accelerated the wound healing process. These in vitro and in vivo experiments confirm that UCBMSCs-released exosomes have tissue regeneration and inflammation suppression properties. Conclusions: This study presents the processes and quality control items that can produce exosomes as drugs in good manufacturing practice facilities and shows the possibility of developing drugs for various diseases based on the inherent efficacy of UCBMSCs-released exosomes. This study is the first to show how exosomes can be produced and quality-validated in a GMP facility for use as drugs, which will accelerate the time to market for future exosomes base bio-new drug.