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Trial Results Suggest Safety of Trisomy 7 MSCs in Treating Meniscus Injuries

Previous research from the laboratory of Ichiro Sekiya (Tokyo Medical and Dental University, Tokyo, Japan) described the development of a mesenchymal stem cell (MSC)-based therapy for the treatment of meniscus injuries [1]. Importantly, MSCs can often display trisomy of chromosome 7 in older donors [2-7], which can prompt tumor formation [8]. In their recent STEM CELLS Translational Medicine article, researchers from the Sekiya group now report on the proportion of synovial MSCs with trisomy 7 in patients undergoing cell therapy, the relative safety of MSCs with trisomy 7, and the rate of tumor formation in patients at five years after cell therapy [9]. Overall, Mizuno et al. establish that the presence of trisomy 7 in transplanted synovial MSCs may not entail any significant problems from a safety point of view.

An initial analysis of the autologous synovial MSCs employed in the transplants using G-bands and digital karyotyping encountered trisomy 7 in three of the ten patients; in these cases, between 5 and 10% of synovial MSCs showed trisomy 7. Interestingly, a transcriptional comparison of MSCs with and without trisomy 7 failed to encounter the differential expression of representative oncogenes (i.e., CDKN1A, CDKN2A, MYC, and KIT) or chromosome 7-resident genes (i.e., EGFR, HGF, IL6, PPIA, and CAV2); furthermore, subsequent whole-genome sequencing, DNA methylation analysis, and proliferation assays also failed to detect significant differences between the two cell populations. Looking beyond safety, an assessment of in vitro analysis highlighted a similar degree of chondrogenic potential in MSCs with and without trisomy 7.

Subsequent in vivo confirmatory analysis demonstrated a lack of tumorigenic potential of human synovial MSCs with trisomy 7 after transplantation into mouse knees. Meanwhile, the five-year follow-ups of the ten human patients found that the meniscus tear became obscured after three years (by magnetic resonance imaging), but also underscored a lack of serious adverse events (including tumorigenesis), including in the three patients who received MSCs with trisomy 7.

While the results of this study strongly suggest the safety of autologous synovial MSC transplantation into the knee as a therapy for meniscus injuries, the authors do note some limitations with their study. The most critical limitation they highlight relates to the relatively small amount of MSCs containing trisomy 7, which may inhibit the detection of some phenotypes.

For more on the safety and efficacy of MSC therapy and the impact of trisomy 7, stay tuned to the Stem Cells Portal!


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