Introduction

Residual pluripotent stem cells (PSC) within differentiated populations are problematic because of their potential to form tumors. Simple methods to reduce their occurrence are needed.

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 pO_2.

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.

中文翻译：

---

生理氧下小鼠多能干细胞分化减少残留畸胎瘤

介绍

分化群体中残留的多能干细胞 (PSC) 是有问题的，因为它们有可能形成肿瘤。需要简单的方法来减少它们的发生。

方法

在这里，我们证明了将氧分压 (pO ₂ ) 控制到发育中胚胎的典型生理水平，通过在高透氧性基质上进行培养，降低了 PSC 在内部的比例和分化群体的致瘤潜力。

结果

对于小鼠 PSC (mPSC) ，在低 pO ₂下的分化和/或扩展培养可将测量的多能性标记减少多达四个数量级。与细胞分选相结合将减少量提高到六个数量级。植入免疫功能低下的小鼠后，在低 pO ₂下分化的 mPSC要么不形成肿瘤，要么以比高 pO _{2 慢的速度形成肿瘤。}

结论

单独的低 pO ₂培养或与其他方法结合是一种潜在的简单方法，可应用于未来的细胞治疗方案，以最大限度地减少肿瘤形成的可能性。