PainRelief.com Interview with:
Mitsuru Mizuno, DVM, Ph.D.
Assistant professor at CSCRM,
Principal investigator for this study
and Ichiro Sekiya, M.D., Ph.D..
PainRelief.com: What is the background for this study? What are the main findings? How are the stem cells obtained?
Response: We have developed a cell therapy for treating difficult-to-heal meniscus injury using mesenchymal stem cells (MSCs) derived from the synovium of the knee. However, trisomy 7 is often found in synovial cells obtained from patients with osteoarthritis, a disease that occurs with aging.
PainRelief.com: What are the main findings?
Response: We recruited 10 patients for the study and transplanted their own stem cells into the affected knee joints, then followed up with MRIs over the next five years. The images revealed that tears in the patients’ knee meniscus were obscured three years after transplantation. We also identified trisomy 7 in three of the patients, yet no serious adverse events including tumor formation were observed in any of them.
Interestingly, the mRNA expressions of representative oncogenes and genes on chromosome 7 did not differ between MSCs with and without trisomy 7. Whole-genome sequencing and DNA methylation analysis showed similar results for MSCs with and without trisomy 7. Transplantation of human synovial MSCs with trisomy 7 into 8 mouse knees did not result in tumor formation under the skin or in the knees after 8 weeks in any mouse. In vitro chondrogenic potentials were similar between MSCs with and without trisomy 7.
PainRelief.com: What should readers take away from your report?
Response: The present results suggest that transplantation of autologous synovial MSCs into the knee joint does not cause serious problems, since in vivo chromosomal aneuploidy is preserved if the number of passages is small. However, the type of problems that may arise in the case of allogeneic transplantation is not known. Even when MSCs are derived from the same cell source, different types of risks may exist depending on the route of transplantation. Therefore, each therapeutic target requires its own risk management strategy.
Synovial MSCs transplanted into a joint, as in this case, remain in the joint and have little effect on the whole body. However, MSCs administered intravenously can adhere to various tissues, such as the lungs, where they are maintained for a long time, so they may present as yet unknown risks in the future. The results of this study do not indicate that a uniform management approach can be applied without consideration of the type or method of administration of MSCs.
PainRelief.com: What recommendations do you have for future research as a result of this work?
Response: The maximum proportion of trisomy 7 in synovial MSCs was only 10%. This proportion might have been too small to detect phenotypes of synovial MSCs with trisomy 7, or the phenotypes might have been silenced on the chromosome. Further clarification will require simultaneous analysis of single-cell genome sequencing and single-cell mRNA analysis.
Mizuno, M, Endo, K, Katano, H, et al. Transplantation of human autologous synovial mesenchymal stem cells with trisomy 7 into the knee joint and 5 years of follow-up. STEM CELLS Transl Med. 2021; 1- 14. https://doi.org/10.1002/sctm.20-0491
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