Mouse Pluripotent Stem Cell Differentiation Under Physiological Oxygen Reduces Residual Teratomas

小鼠多能干细胞在生理氧条件下分化可减少残留畸胎瘤

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作者:Jeffrey R Millman, Jit Hin Tan, Clark K Colton

Conclusions

Low pO2 culture alone or in combination with other methods is a potentially straightforward method that could be applied to future cell therapy protocols to minimize the possibility of tumor formation.

Methods

Here, we demonstrate that control of the oxygen partial pressure (pO2) to physiological levels typical of the developing embryo, enabled by culture on a highly oxygen permeable substrate, reduces the fraction of PSC within and the tumorigenic potential of differentiated populations.

Results

Differentiation and/or extended culture at low pO2 reduced measured pluripotency markers by up to four orders of magnitude for mouse PSCs (mPSCs). Combination with cell sorting increased the reduction to as much as six orders of magnitude. Upon implantation into immunocompromised mice, mPSCs differentiated at low pO2 either did not form tumors or formed tumors at a slower rate than at high pO2. Conclusions: Low pO2 culture alone or in combination with other methods is a potentially straightforward method that could be applied to future cell therapy protocols to minimize the possibility of tumor formation.

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