Chromosomal variability of human mesenchymal stem cells cultured under hypoxic conditions.
Bottom Line: Bone marrow derived human mesenchymal stem cells (hMSCs) have attracted great interest from both bench and clinical researchers because of their pluripotency and ease of expansion ex vivo.However, these cells do finally reach a senescent stage and lose their multipotent potential.The safe, rapid expansion of hMSCs is critical for their clinical application.
Affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshidakonoecho, Sakyo-ku, Kyoto, Japan.Show MeSH
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Mentions: We compared spontaneous transformations in cells cultured under normal-oxygen (20%) and low-oxygen (5%) conditions. Figure 3A shows aberration-free survival curves for occurrence of spontaneous chromosomal aberrations as an end-point throughout in vitro expansion, which is estimated using the Kaplan–Meier method. In survival analysis, once abnormal karyotypes are detected or follow-up time is ended, the donor becomes not at risk. Under hypoxia, spontaneous transformations were detected in earlier passages than under normoxic conditions, which was statistically significant (log-rank test; P = 0.032). Overall increased risk of spontaneous transformations under hypoxic conditions was estimated at 2.70 (95% CI, 1.01–8.10) compared with normoxic conditions, presented as odds ratios in Table 2. Smoothed hazard modelling for occurrence of chromosomal aberrations illustrated the increased hazard risk after passage 4 in both sets of culture conditions (Fig. 3B). An increased hazard of primary karyotypic abnormality was detected when donors had hMSCs with an initial anomalous karyotype. We found significant effects of PDL and donor age on the risk of spontaneous transformation after controlling for culture conditions. Incremental risk associated with one increase in PDL was estimated at 1.14 (95% CI, 1.04–1.26) and the risk associated with overall expansion was estimated at 18.6 (95% CI, 2.61–158), as presented by the odds ratios in Table 2. Similarly, donor age range of 50s, 60s and 70s elevated the risk of spontaneous transformations compared with donors in their 40s, at 6.59 (95% CI, 0.99–130), 17.3 (3.00–329) and 7.33 (1.09–146), respectively (Table 2). The confidence intervals of estimated odds ratio for donor age were wide because the sample size was limited in this research.
Affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshidakonoecho, Sakyo-ku, Kyoto, Japan.