Transplantation of Donor-Origin Mouse Embryonic Stem Cell-Derived Thymic Epithelial Progenitors Prevents the Development of Chronic Graft-versus-Host Disease in Mice
Transplantation of Donor-Origin Mouse Embryonic Stem Cell-Derived Thymic Epithelial Progenitors Prevents the Development of Chronic Graft-versus-Host Disease in Mice
复制标题
移植供体来源的小鼠胚胎干细胞来源的胸腺上皮祖细胞可预防小鼠慢性移植物抗宿主病的发生。
DOI：
10.5966/sctm.2016-0012
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发表时间：
2017-01-01
影响因子：
6
通讯作者：
Lai, Laijun
中科院分区：
文献类型：
--
作者：
Hu, Rong;Liu, Yalan;Lai, Laijun
异基因造血干细胞移植（HSCT）是一种治疗多种恶性和非恶性疾病的有效方法。然而，慢性移植物抗宿主病（cGVHD）仍然是异基因HSCT后晚期发病率和死亡率的重要原因。cGVHD通常表现为自身免疫综合征。胸腺上皮细胞（TEC）在支持负选择和调节性T细胞（Treg）产生中起关键作用。研究表明，TEC中的损伤足以诱导cGVHD。我们以前曾报道，小鼠胚胎干细胞（mESCs）可以选择性诱导产生胸腺上皮祖细胞（TEPs）在体外。当移植到体内时，mESC-TEPs进一步发育成支持T细胞发育的TEC。我们在这里表明，供体来源的mESC-TEPs移植到cGVHD受体诱导对供体和宿主抗原的免疫耐受，并防止cGVHD的发展。这与更多的TEC和TdR有关。我们的研究结果表明，胚胎干细胞来源的TEPs可能提供一个新的工具来控制cGVHD。
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many malignant and nonmalignant diseases. However, chronic graft-versus-host disease (cGVHD) remains a significant cause of late morbidity and mortality after allogeneic HSCT. cGVHD often manifests as autoimmune syndrome. Thymic epithelial cells (TECs) play a critical role in supporting negative selection and regulatory T-cell (Treg) generation. Studies have shown that damage in TECs is sufficient to induce cGVHD. We have previously reported that mouse embryonic stem cells (mESCs) can be selectively induced to generate thymic epithelial progenitors (TEPs) in vitro. Whentransplanted in vivo, mESC-TEPs further develop into TECs that support T-cell development. We show here that transplantation of donor-origin mESC-TEPs into cGVHD recipients induces immune tolerance to both donor and host antigens and prevents the development of cGVHD. This is associated with more TECs and Tregs. Our results suggest that embryonic stem cell-derived TEPs may offer a new tool to control cGVHD.