Assessing biodistribution of biomedical cellular product based on human chondrocytes following implantation to BALB/C nude mice

Pikina AS1, Golubinskaya PA1, Ruchko ES2, Kozhenevskaya EV3, Pospelov AD3, Babayev AA3, Eremeev AV1,2
About authors

1 Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia

2 Koltzov Institute of Developmental Biology of Russian Academy of Sciences, Moscow, Russia

3 Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia

Correspondence should be addressed: Arina S. Pikina
Malaya Pirogovskaya, 1а, Moscow, 119435, Russia; ur.xednay@anikip.anira

About paper

Funding: the study was performed under the State Assignment “Chondrosphere”, R&D project ID АААА-А19-119052890054-4.

Acknowledgments: the authors express their gratitude to the research staff of the laboratory of cell biology, Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of FMBA of Russia, for methodological support provided during the study.

Author contribution: Pikina AS — literature review, literature source collection and analysis, manuscript writing; Golubinskaya PA — data acquisition and analysis, manuscript editing; Ruchko ES — data acquisition and analysis; Kozhenevskaya EV — carrying out work at the vivarium; Pospelov AD — histological analysis; Babayev AA — animal experiment management; Eremeev AV — experimental design, final correction of the manuscript. All authors confirm compliance of authorship to ICMJE international criteria.

Compliance with the ethical standards: the study was approved by the Boethics Commission of the Lobachevsky State University of Nizhny Novgorod (protocol № 73 dated 17 April 2023).

Received: 2023-11-05 Accepted: 2023-12-17 Published online: 2023-12-31

Despite the prospects of the approach to cell therapy of cartilage damage in humans involving autologous chondrocytes, similar technologies are just beginning to be introduced into medical practice in the Russian Federation. In this regard, the development of biomedical cell products (BCPs) for cartilage tissue repair is quite topical, while the use of organoid technology is the most close to the native tissue conditions. According to requirements of legislation of the Russian Federation, it is necessary to assess biodistribution characterizing migration potential of the cells, their tropism for body tissues following implantation within the framework of preclinical trials. The study was aimed to assess biodistribution of novel BCP based on human chondrocytes in the form of chondrospheres after subcutaneous implantation in Balb/c nude mice. Implantation to 12 mice was performed during the first phase, along with administration of saline to 12 control animals. Weighting and follow-up were conducted for 90 days. Then mice were withdrawn from the experiment to collect samples of organs and tissues for histological analysis of the implant, estimation of its viability, integration. During the second phase biodistribution was assessed by PCR in order to detect human DNA in the organ and tissue samples. Chondrospheres successfully integrated in the tissues surrounding the inoculation zones and formed cartilage tissue. No significant (p < 0.05) changes in weight were reported. No human DNA found in chondrosphere implantation zones was detected in the samples collected from other organs and tissues. BCP demonstrated no biodistribution across other tissues and organs of mice 90 days after implantation, which suggested that the product developed was safe.

Keywords: preclinical trials, biodistribution, chondrocytes, biomedical cellular product, chondrospheres