Devine Steven M, Cobbs Carrington, Jennings Matt, Bartholomew Amelia, Hoffman Ron
Section of Hematology/Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, USA.
Blood. 2003 Apr 15;101(8):2999-3001. doi: 10.1182/blood-2002-06-1830. Epub 2002 Dec 12.
Ex vivo-expanded mesenchymal stem cells (MSCs) were transduced with a green fluorescent protein (GFP) retroviral construct and subsequently infused into 3 adult baboons following lethal total body irradiation and hematopoietic support or without any prior conditioning. To study the long-term fate of these MSCs, necropsies were performed between 9 and 21 months following MSC infusion, and an average of 16 distinct tissues were recovered from each recipient and evaluated for the presence of the GFP transgene in purified genomic DNA by sensitive real-time polymerase chain reaction (PCR). Two baboons received autologous and one allogeneic GFP-transduced MSCs. Both allogeneic and autologous MSCs appeared to distribute in a similar manner. Gastrointestinal tissues harbored high concentrations of transgene per microgram of DNA. Additional tissues including kidney, lung, liver, thymus, and skin were also found to contain relatively high amounts of DNA equivalents. Estimated levels of engraftment in these tissues ranged from 0.1% to 2.7%. The nonconditioned recipient appeared to have less abundant engraftment. These data suggest that MSCs initially distribute broadly following systemic infusion and later may participate in ongoing cellular turnover and replacement in a wide variety of tissues.
用绿色荧光蛋白(GFP)逆转录病毒构建体转导体外扩增的间充质干细胞(MSC),随后在致死性全身照射和造血支持后或无任何预处理的情况下,将其注入3只成年狒狒体内。为了研究这些MSC的长期命运,在注入MSC后9至21个月进行尸检,从每个受体中平均回收16个不同组织,并通过灵敏的实时聚合酶链反应(PCR)评估纯化基因组DNA中GFP转基因的存在情况。两只狒狒接受了自体和一只接受了同种异体GFP转导的MSC。同种异体和自体MSC的分布方式似乎相似。胃肠道组织每微克DNA含有高浓度的转基因。还发现包括肾脏、肺、肝脏、胸腺和皮肤在内的其他组织含有相对大量的DNA当量。这些组织中的估计植入水平为0.1%至2.7%。未预处理的受体植入情况似乎较少。这些数据表明,MSC全身注入后最初广泛分布,随后可能参与多种组织中正在进行的细胞更新和替代。