Mouse embryonic stem cell-derived thymic epithelial cell progenitors enhance T-cell reconstitution after allogeneic bone marrow transplantation
Mouse embryonic stem cell-derived thymic epithelial cell progenitors enhance T-cell reconstitution after allogeneic bone marrow transplantation
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DOI：
10.1182/blood-2011-03-340794
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发表时间：
2011-09-22
期刊：
影响因子：
20.3
通讯作者：
Zhao, Yong
中科院分区：
文献类型：
--
作者：
Lai, Laijun;Cui, Cheng;Zhao, Yong
我们已经报道了小鼠胚胎干细胞（mESCs）可以在体外选择性诱导分化为胸腺上皮细胞祖细胞（TEPs）。当放置在体内时，这些mesc来源的TEPs分化为皮质和髓质胸腺上皮细胞，重建正常的胸腺结构，并在同源骨髓移植（BMT）后增强胸腺细胞再生。在这里，我们发现mesc来源的TEPs移植可以有效地建立胸腺细胞嵌合，并在年轻和年老的同种异体骨髓移植受体中产生幼稚T细胞。GVHD未被诱导，而移植物抗肿瘤活性显著增强。重要的是，重组的免疫系统对宿主、mESC和骨髓移植供体抗原具有耐受性。因此，esc来源的TEPs可能为BMT后快速持久地纠正t细胞免疫缺陷以及诱导对esc来源的组织和器官移植的耐受提供了一种新的方法。此外，esc衍生的TEPs也可以作为逆转年龄依赖性胸腺退化的手段，从而增强免疫功能并降低老年人的感染率。(血。2011;118 (12):3410 - 3418)
We have reported that mouse embryonic stem cells (mESCs) can be selectively induced in vitro to differentiate into thymic epithelial cell progenitors (TEPs). When placed in vivo, these mESC-derived TEPs differentiate into cortical and medullary thymic epithelial cells, reconstitute the normal thymic architecture, and enhance thymocyte regeneration after syngeneic BM transplantation (BMT). Here, we show that transplantation of mESC-derived TEPs results in the efficient establishment of thymocyte chimerism and subsequent generation of naive T cells in both young and old recipients of allogeneic BM transplant. GVHD was not induced, whereas graft-versus-tumor activity was significantly enhanced. Importantly, the reconstituted immune system was tolerant to host, mESC, and BM transplant donor antigens. Therefore, ESC-derived TEPs may offer a new approach for the rapid and durable correction of T-cell immune deficiency after BMT, and the induction of tolerance to ESC-derived tissue and organ transplants. In addition, ESC-derived TEPs may also have use as a means to reverse age-dependent thymic involution, thereby enhancing immune function and decreasing infection rates in the elderly. (Blood. 2011;118(12):3410-3418)