人源化小鼠对人多能干细胞治疗的同种免疫反应。

Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics.

机构信息

Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA; Department of Medicine, Stanford University School of Medicine, Stanford, California, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA; Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.

出版信息

Cell Rep. 2017 Aug 22;20(8):1978-1990. doi: 10.1016/j.celrep.2017.08.003.

There is growing interest in using embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives. Furthermore, using an "allogenized" mouse model, we show the feasibility of reconstituting immunodeficient mice with a functional mouse immune system and describe a key role of innate immune cells in the rejection of mouse stem cell allografts.

人们越来越感兴趣地使用胚胎干细胞 (ESC) 和诱导多能干细胞 (iPSC) 衍生物进行组织再生。然而，为了维持长期移植物的持久性，有必要加深对人类免疫系统对干细胞衍生同种异体移植物的反应的理解。为了模拟这种同种异体免疫，用人造血和免疫细胞移植的人源化小鼠可能会被证明是有用的。在这项研究中，对移植物浸润的人淋巴细胞和脾细胞的深入分析表明，人源化小鼠不能完全模拟人类对同种异体干细胞及其衍生物的免疫反应。此外，我们使用“同种异体化”小鼠模型，展示了用功能性小鼠免疫系统重建免疫缺陷小鼠的可行性，并描述了固有免疫细胞在排斥小鼠干细胞同种异体移植物中的关键作用。