Study of the Biodistribution of a Tissue-Engineered Product Based on Human Chondrocytes of Various Sources After Implantation into Balb/c Nude Mice

In this research, we develop a tissue-engineered product (TEP) based on chondrocytes of various genesis in the form of 3D structures (chondrospheres) after subcutaneous implantation in immunodeficient Balb/c Nude mice and investigate its biodistribution profile. Initially, chondrospheres based on chondrocytes and chondrocytes from differentiated induced pluripotent stem cells (iPSCs), including lines with a knockout of the β2m gene, were implanted. The animals were monitored for nine months. Further, after euthanasia, organ and tissue samples were obtained for histological analysis, evaluation of the viability of the implant, its integration and biodistribution research by PCR. Chondrospheres from differentiated iPSCs derivatives of both types successfully integrated into the surrounding tissues in the inoculation zones and formed cartilage tissue. In the samples near the implantation zone of the experimental groups of animals, no human DNA was detected. Human DNA was found in the samples of organs of the control groups (introduction of MDA231 and mesenchymal stem cells). Thus, three and nine months after implantation, the studied TEP samples demonstrated the absence of biodistribution to other tissues and organs of mice, which indicates the safety of the drug being developed.