Mitochondrial DNA (mtDNA) mutations occur naturally in skeletal muscle fibers from aged rhesus macaques. In addition, mtDNA mutations have been observed in germinal vesicle oocytes from fertile monkeys. The goal of this study was to determine whether the rhesus macaque mitochondrial common deletion was present in oocytes and embryos generated by in-vitro embryo production (IVP), as well as in rhesus adult and embryonic stem cell lines. The rhesus common deletion was detected in IVP-generated embryos, three IVP-derived embryonic stem cell lines (ORMES 1, 2 and 7), one in-vivo-derived embryonic stem cell line (R4) and multiple passages of an adult bone marrow stromal cell (BMSC) line. Mitochondrial DNA from an adult adipose stromal cell (ATSC) line was compared with mtDNA from an immortalized line transfected with a retroviral vector expressing telomerase, ATSC-TERT. Multiple passages of the ATSC line harboured a dramatically higher level of the rhesus common deletion than the immortalized ATSC-TERT line. Accumulation of mtDNA mutations in oocytes, embryos and subsequent embryonic stem cell lines, as well as adult stem cell lines, may contribute to mitochondrial dysfunction, and thereby impair ATP production. The authors believe this information establishes a compelling argument for the parallel development of embryonic stem cell technology in non-human primates and humans.
Despite acknowledgement in the scientific community of sex-based differences in cartilage biology, the implications for study design remain unclear, with many studies continuing to arbitrarily assign demographics. Clinically, it has been well-established that males and females differ in cartilage degeneration, and accumulating evidence points to the importance of sex differences in the field of cartilage repair. However, a comprehensive review of the mechanisms behind this trend and the influence of sex on cartilage regeneration has not yet been presented. This paper aims to summarize current findings regarding sex-dependent variation in knee anatomy, sex hormones’ effect on cartilage, and cartilaginous degeneration and regeneration, with a focus on stem cell therapies. Findings suggest that the stem cells themselves, as well as their surrounding microenvironment, contribute to sex-based differences. Accordingly, this paper underscores the contribution of both stem cell donor and recipient sex to sex-related differences in treatment efficacy. Cartilage regeneration is a field that needs more research to optimize strategies for better clinical results; taking sex into account could be a big factor in developing more effective and personalized treatments. The compilation of this information emphasizes the importance of investing further research in sex differences in cartilage biology.
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