A Toxicity study of exosomes derived from mesenchymal stem cells

Abstract

Background & Aim Exosomes are being developed as therapeutics including regenerative and immune-modulatory therapies, and drug delivery vehicles. Especially, mesenchymal stem cells-derived exosomes (MSC-Exo) have been suggested and highlighted as therapeutics for variety of human diseases. For the development of therapeutics, toxicity evaluation is the important first step in the nonclinical phase to ensure the safety of exosome therapeutics. Currently, the efficacies of MSC-Exo have been verified in a variety of disease animal models, but the toxicity evaluation is limited. The aim of this study was to evaluate toxicological profiles with MSC-Exo in according to the OECD guidelines and GLP regulation. Methods, Results & Conclusion We conducted toxicological studies of MSC-Exo according to the OECD guidelines such as skin sensitization (OECD TG 442B), photosensitization (OECD TG 432), eye irritation (OECD TG 437), skin irritation (OECT TG 439), and acute oral toxicity studies (OECD TG 423). As results, MSC-Exo were classified as a potential non-sensitizer in skin sensitization test, UN GHS no category in eye irritation test, and a skin non-irritant in skin irritation test, respectively. Additionally, MSC-Exo did not induce any toxicity in phototoxicity test and acute oral toxicity test. MSC-Exo have proven to be safe without side effects when topical treatment on skin, and can be applied for the development of exosomes therapeutics for topical formulation. Exosomes are being developed as therapeutics including regenerative and immune-modulatory therapies, and drug delivery vehicles. Especially, mesenchymal stem cells-derived exosomes (MSC-Exo) have been suggested and highlighted as therapeutics for variety of human diseases. For the development of therapeutics, toxicity evaluation is the important first step in the nonclinical phase to ensure the safety of exosome therapeutics. Currently, the efficacies of MSC-Exo have been verified in a variety of disease animal models, but the toxicity evaluation is limited. The aim of this study was to evaluate toxicological profiles with MSC-Exo in according to the OECD guidelines and GLP regulation. We conducted toxicological studies of MSC-Exo according to the OECD guidelines such as skin sensitization (OECD TG 442B), photosensitization (OECD TG 432), eye irritation (OECD TG 437), skin irritation (OECT TG 439), and acute oral toxicity studies (OECD TG 423).