The evidence of a macrophage barrier in the xenotransplantation of human hematopoietic stem cells to severely immunodeficient rats
The evidence of a macrophage barrier in the xenotransplantation of human hematopoietic stem cells to severely immunodeficient rats
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人类造血干细胞异种移植至严重免疫缺陷大鼠中巨噬细胞屏障的证据
DOI：
10.1111/xen.12702
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发表时间：
2021
影响因子：
3.9
通讯作者：
Oda Tatsuya
中科院分区：
文献类型：
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作者：
Furuya Kinji;Zheng Yun-Wen;Ge Jian-Yun;Zhang Ludi;Furuta Tomoaki;Liang Chen;Abe Haruna;Yagi Hiroya;Hamada Hiromi;Isoda Hiroko;Hui Lijian;Ohkohchi Nobuhiro;Oda Tatsuya
背景与人-鼠造血干细胞移植（human-to-rat hematopoietic stem cell transplantation，HSCT）模型不同，人-鼠造血干细胞移植（human-to-rat hematopoietic stem cell transplantation，HSCT）模型较为罕见。特别是在生理学、毒理学和药理学领域，需要大鼠模型。除了淋巴细胞外，巨噬细胞也被认为对异种移植很重要。我们产生了一个大鼠异种移植模型，以证明巨噬细胞作为异种transplantation barrier.MethodsImmunodeficiency在SRG大鼠，这是Sprague-Dawley（SD）大鼠lackingRag 2和IL 2 rg，通过流式细胞术和脾脏免疫染色证实。在筑波大学医院预定剖宫产后收集人脐带血。将脐带血单核细胞（CB-MNC）移植到SRG大鼠中，给予多次注射氯膦酸盐脂质体（CL），导致巨噬细胞耗竭。通过流式细胞术观察人细胞的存活。进行大鼠巨噬细胞吞噬试验以检查大鼠巨噬细胞对注射的人/大鼠血细胞的种属特异性作用。ResultsSRG大鼠缺乏T/B/NK细胞。在没有CL预处理的情况下，在移植后7小时内从SRG大鼠中取出人CB-MNC。经CL预处理的大鼠移植后可存活。仅在一次性CL注射后观察到生存期延长超过4周。大鼠巨噬细胞具有种属特异性的潜力，吞噬人体血细胞在vivo.ConclusionIn人-大鼠HSCT，早期巨噬细胞控制，导致巨噬细胞免疫耐受的短期，是重要的植入。所生成的模型可用于创建未来的异种移植模型或其他临床研究。
BackgroundThe human‐to‐rat hematopoietic stem cell transplantation (HSCT) model is rare, unlike its human‐to‐mouse counterpart. The rat models are desired, especially in areas of physiology, toxicology, and pharmacology. In addition to lymphocytes, macrophages are also considered to be important for xenotransplantation. We generated a rat xenotransplantation model to prove the role of macrophages as a xenotransplantation barrier.MethodsImmunodeficiency in SRG rats, which are Sprague–Dawley (SD) rats lackingRag2andIl2rg, was confirmed by flow cytometry and spleen immunostaining. Human umbilical cord blood was collected after scheduled cesarean section at the University of Tsukuba Hospital. Cord blood mononuclear cells (CB‐MNCs) were transplanted into the SRG rats administered several injections of clodronate liposome (CL), which cause macrophage depletion. Survival of human cells was observed by flow cytometry. Rat macrophage phagocytosis assay was performed to check the species‐specific effects of rat macrophages on injected human/rat blood cells.ResultsSRG rats were deficient in T/B/NK cells. Without CL pretreatment, human CB‐MNCs were removed from SRG rats within 7 hours after transplantation. The rats pretreated with CL could survive after transplantation. Prolonged survival for more than 4 weeks was observed only following a one‐time CL injection. Rat macrophages had a species‐specific potential for the phagocytosis of human blood cells in vivo.ConclusionIn human‐to‐rat HSCT, the short period of early macrophage control, leading to macrophage immunotolerance, is important for engraftment. The generated model can be useful for the creation of future xenotransplantation models or other clinical research.