Guillot Pascale V, Gotherstrom Cecilia, Chan Jerry, Kurata Hiroshi, Fisk Nicholas M
Experimental Fetal Medicine Group, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, U.K.
Stem Cells. 2007 Mar;25(3):646-54. doi: 10.1634/stemcells.2006-0208. Epub 2006 Nov 22.
The biological properties of stem cells are key to the success of cell therapy, for which MSC are promising candidates. Although most therapeutic applications to date have used adult bone marrow MSC, increasing evidence suggests that MSC from neonatal and mid-gestational fetal tissues are more plastic and grow faster. Fetal stem cells have been isolated earlier in development, from first-trimester blood and hemopoietic organs, raising the question of whether they are biologically closer to embryonic stem cells and thus have advantages over adult bone marrow MSC. In this study, we show that human first-trimester fetal blood, liver, and bone marrow MSC but not adult MSC express the pluripotency stem cell markers Oct-4, Nanog, Rex-1, SSEA-3, SSEA-4, Tra-1-60, and Tra-1-81. In addition, fetal MSC, irrespective of source, had longer telomeres (p < .001), had greater telomerase activity (p < .01), and expressed more human telomerase reverse transcriptase (p < .01). Fetal MSC were also more readily expandable and senesced later in culture than their adult counterparts (p < .01). Compared with adult MSC, first-trimester fetal tissues constitute a source of MSC with characteristics that appear advantageous for cell therapy.
干细胞的生物学特性是细胞治疗成功的关键,间充质干细胞(MSC)是很有前景的候选细胞。尽管迄今为止大多数治疗应用都使用成人骨髓间充质干细胞,但越来越多的证据表明,来自新生儿和妊娠中期胎儿组织的间充质干细胞更具可塑性且生长更快。胎儿干细胞在发育早期就已从孕早期血液和造血器官中分离出来,这就引发了一个问题,即它们在生物学上是否更接近胚胎干细胞,从而比成人骨髓间充质干细胞具有优势。在本研究中,我们发现人类孕早期胎儿血液、肝脏和骨髓间充质干细胞而非成人间充质干细胞表达多能干细胞标志物Oct-4、Nanog、Rex-1、SSEA-3、SSEA-4、Tra-1-60和Tra-1-81。此外,无论来源如何,胎儿间充质干细胞的端粒更长(p <.001),端粒酶活性更高(p <.01),并且表达更多的人类端粒酶逆转录酶(p <.01)。与成人间充质干细胞相比,胎儿间充质干细胞在培养中也更容易扩增且衰老更晚(p <.01)。与成人间充质干细胞相比,孕早期胎儿组织构成了一种间充质干细胞来源,其特性似乎对细胞治疗有利。