人脂肪源性间充质干细胞的体内分布

Stem Cells. 2006 Sep 7; （IF 6.094）

        使用3种异种移植模型：NOD/SCID，nude/NOD/SCID，NOD/SCID/MPSVII 小鼠来检测人脂肪源性间充质干细胞（AMSC）的多向分化潜能。增强绿色荧光蛋白（eGFP）被逆转录病毒导入纯化的AMSC以鉴别移植后的细胞。转染后的细胞通过静脉、腹腔和皮下注入亚致死剂量辐照的免疫缺陷小鼠体内。移植后75天，收获组织，DNA PCR检测特定的载体序列和人Alu重复序列。双定量PCR用于检测人B－球蛋白和小鼠RAPSYN引物来评估人类细胞在各个组织的分布。新NOD/SCID/MPSVII小鼠作为受体可允许使用酶反应迅速鉴别人体细胞而不依赖表面蛋白和外源基因的转染。移植后75天，在多种组织中可检测到供体来源的细胞，各种给药途径的结果是一致的而且不依赖转染率。组织定位研究显示初始MSC并没有在宿主体内大量增殖。我们认为人AMSC是一种移植后具有独特组织分布模型的干细胞种群。AMSC易于获得并便于逆转录病毒的转染，使它们成为一种可用于多种的终末靶组织优秀的细胞治疗途径。

In vivo Distribution of Human Adipose-Derived MSC.

Meyerrose TE, De Ugarte DA, Hofling AA, Herrbrich PE, Cordonnier TD, Shultz LD, Eagon JC, Wirthlin L, Sands MS, Hedrick MA, Nolta JA. 

Division of Oncology, Hematopoietic Development and Malignancy Section, Saint Louis, Missouri.

The potential for human adipose-derived mesenchymal stem cells (AMSC) to traffic into various tissue compartments was examined using three murine xenotransplantation models: NOD/SCID, nude/NOD/SCID and NOD/SCID/MPSVII mice. Enhanced green fluorescent protein (eGFP) was introduced into purified AMSC via retroviral vectors to assist in identification of cells post-transplantation. Transduced cells were administered to sub-lethally irradiated immune deficient mice through intravenous, intraperitoneal, or subcutaneous injection. Up to 75 days post-transplantation, tissues were harvested and DNA PCR was performed for specific vector sequences as well as for human Alu repeat sequences. Duplex quantitative PCR using human B-globin and murine RAPSYN primers assessed the contribution of human cells to each tissue. The use of the novel NOD/SCID/MPSVII mouse as a recipient allowed rapid identification of human cells in the murine tissues, using an enzyme reaction that was independent of surface protein expression or transduction with an exogenous transgene. For up to 75 days post-transplantation, donor-derived cells were observed in multiple tissues, consistently across the various administration routes and independent of transduction parameters. Tissue localization studies showed that the primary MSC did not proliferate extensively at the sites of lodgement. We conclude that human AMSC represent a population of stem cells with a ubiquitous pattern of tissue distribution after administration. AMSC are easily obtained and highly amenable to current transduction protocols for retroviral transduction, making them an excellent avenue for cell-based therapies that involve a wide range of end tissue targets.