Generation of human/rat xenograft animal model for the study of human donor stem cell behaviors in vivo
Generation of human/rat xenograft animal model for the study of human donor stem cell behaviors in vivo作者机构：Center of Experimental Animals Sun Yat-sen University Guangzhou 510080 Guangdong Province China Institute of Comparative Medicine and Center of Experimental Animals Southern Medical University Guangzhou 510515 Guangdong Province China Clinic Experimental Department Kunming General Hospital Chengdu Military District of PLA Kunming 650032 Yunnan Province China
出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)
年 卷 期：2007年第13卷第19期
页 面：2707-2716页
核心收录：
学科分类：1001[医学-基础医学(可授医学、理学学位)] 08[工学] 100101[医学-人体解剖与组织胚胎学] 09[农学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种] 10[医学]
基 金：Supported by The National Natural Science Foundation of China, No. 30271177 and No. 39870676 the National 9th Five-year Program, No. 101033 The Major Science and Technology Projects of Guangdong Province, No. B602 Natural Science Foundation of Guangdong Province, No. 021903 The Postdoctoral Fellowship Foundation of China (Series 29) The Special Fund of Scientifi c Instrument Collaborative Share-net in Guangzhou, No. 2006176
主 题：Human umbilical cord blood-derived cells In utero xenogeneic transplantation Human-rat chimeras Embryonic microenvironment In vivo model
摘 要：AIM： TO accurately and realistically elucidate human stem cell behaviors in vivo and the fundamental mechanisms controlling human stem cell fates in vivo, which is urgently required in regenerative medicine and treatments for some human diseases, a surrogate human-rat chimera model was developed. METHODS： Human-rat chimeras were achieved by in utero transplanting low-density mononuclear cells from human umbilical cord blood into the fetal rats at 9-11 d of gestation, and subsequently, a variety of methods, including flow cytometry, PCR as well as immunohistochemical assay, were used to test the human donor contribution in the recipients. RESULTS： Of 29 live-born recipients, 19 had the presence of human CD45^＋ cells in peripheral blood （PB） detected by flow cytometry, while PCR analysis on genomic DNA from 11 different adult tissues showed that 14 selected from flow cytometry-positive 19 animals possessed of donor-derived human cell engraftment in multiple tissues （i.e. liver, spleen, thymus, heart, kidney, blood, lung, muscle, gut and skin） examined at the time of tissue collection, as confirmed by detecting human 132- microglobulin expression using immunohistochemistry. Tn this xenogeneic system, the engrafted donor-derived human cells persisted in multiple tissues for at least 6 mo after birth. Moreover, transplanted human donor cells underwent site-specific differentiation into CK18-positive human cells in chimeric liver and CEHS-positive human cells in chimeric spleen and thymus of recipients. CONCLUSION： Taken together, these findings suggest that we successfully developed human-rat chimeras, in which xenogeneic human cells exist up to 6 mo later. This humanized small animal model, which offers an in vivo environment more closely resembling to the situations in human, provides an invaluable and effective approach for in vivo investigating human stem cell behaviors, and further in vivo examining fundamental mechanisms controlling human stem cell fates in the fut
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