Toxicological Evaluation of Human Adipose-derived Mesenchymal Stem Cells (hADSCs) and hADSCs-derived Exosomes

Autor: Xin-Liao Zhang, Yang Zhou, Pei-Xin Li, Jian Cheng, Jun Zhang, Yu Fu, Yi-jun Lu, Jing Zhang, Ning-Yan Zhang, Bo Zhao
Rok vydání: 2021
Předmět:
DOI: 10.21203/rs.3.rs-626854/v1
Popis: Background: Human adipose tissue-derived stem cells (hADSCs) are considered an ideal source of cells for regenerative medicine. Mesenchymal stem cells derived-exosomes (MSC-Exos) are being opined as new cell-free therapeutics for numerous human diseases. For future clinical applications, the safety of allogenic hADSCs and hADSCs-derived exosomes (hADSCs-Exos) needs to be addressed and verified in pre-clinical animal models. This study sought to evaluate the toxicity of hADSCs and hADSCs-Exos by performing in vivo and in vitro toxicological assessments.Methods: We used IVIS to track the biodistribution of GFP-labeled hADSCs and the PKH26-labeled in a mouse model. The tumorigenicity of hADSCs and hADSCs-Exos was analyzed by soft agar colony formation assay and nude mice tumorigenicity test in vitro and in vivo. The acute animal toxicity and allergenicity test were used to explore the toxicological profile of hADSCs and hADSCs-Exos in mice.Results: We found that hADSCs-Exos accumulated faster in the tissues of mice and were also cleared more rapidly compared to hADSCs. Both hADSCs and hADSCs-Exos have little risk of tumorigenicity, and hADSCs-Exos had lower toxicity and lower immunogenicity than hADSCs.Conclusion: Our study is the first to compare the safety between hADSCs and hADSCs-Exos, and revealed that hADSCs-Exos are safer for application as systemic therapy, without complications in toxicological assessment, and have a better prospective utility as a treatment agent and for drug delivery.
Databáze: OpenAIRE