Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell Stem Cell. 2011 Mar 4;8(3):309-17. doi: 10.1016/j.stem.2011.01.012.
Embryonic stem cells (ESCs) are an attractive source for tissue regeneration and repair therapies because they can be differentiated into virtually any cell type in the adult body. However, for this approach to succeed, the transplanted ESCs must survive long enough to generate a therapeutic benefit. A major obstacle facing the engraftment of ESCs is transplant rejection by the immune system. Here we show that blocking leukocyte costimulatory molecules permits ESC engraftment. We demonstrate the success of this immunosuppressive therapy for mouse ESCs, human ESCs, mouse induced pluripotent stem cells (iPSCs), human induced pluripotent stem cells, and more differentiated ESC/(iPSCs) derivatives. Additionally, we provide evidence describing the mechanism by which inhibition of costimulatory molecules suppresses T cell activation. This report describes a short-term immunosuppressive approach capable of inducing engraftment of transplanted ESCs and iPSCs, providing a significant improvement in our mechanistic understanding of the critical role costimulatory molecules play in leukocyte activation.
胚胎干细胞（ESCs）是组织再生和修复疗法的有吸引力的来源，因为它们可以分化为成年体内几乎任何类型的细胞。然而，为了使这种方法取得成功，移植的 ESCs 必须存活足够长的时间才能产生治疗效果。ESCs 移植面临的主要障碍是免疫系统的移植排斥。在这里，我们表明阻断白细胞共刺激分子允许 ESC 植入。我们证明了这种免疫抑制疗法对小鼠 ESCs、人类 ESCs、小鼠诱导多能干细胞（iPSCs）、人类诱导多能干细胞以及更分化的 ESC/(iPSCs)衍生物的成功。此外，我们提供了证据描述了抑制共刺激分子抑制 T 细胞激活的机制。本报告描述了一种短期免疫抑制方法，能够诱导移植的 ESCs 和 iPSCs 的植入，大大提高了我们对共刺激分子在白细胞激活中发挥关键作用的机制理解。
