Kucia M, Wysoczynski M, Ratajczak J, Ratajczak M Z
Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Cell Tissue Res. 2008 Jan;331(1):125-34. doi: 10.1007/s00441-007-0485-4. Epub 2007 Sep 9.
Bone marrow (BM) develops in mammals by the end of the second/beginning of the third trimester of gestation and becomes a major hematopoietic organ in postnatal life. The alpha-chemokine stromal derived factor-1 (SDF-1) to CXCR4 (G ai-protein-coupled seven transmembrane-spanning chemokine receptor) axis plays a major role in BM colonization by stem cells. By the end of the second trimester of gestation, BM becomes colonized by hematopoietic stem cells (HSC), which are chemoattracted from the fetal liver in a CXCR4-SDF-1-dependent manner. Whereas CXCR4 is expressed on HSC, SDF-1 is secreted by BM stroma and osteoblasts that line BM cavities. Mounting evidence indicates that BM also contains rare CXCR4(+) pluripotent stem cells (PSC). Recently, our group has identified a population of CXCR4(+) very small embryonic like stem cells in murine BM and human cord blood. We hypothesize that these cells are deposited during development in BM as a mobile pool of circulating PSC that play a pivotal role in postnatal tissue turnover, both of non-hematopoietic and hematopoietic tissues.
在哺乳动物中,骨髓在妊娠中期第二个月末/第三个月初开始发育,并在出生后成为主要的造血器官。α趋化因子基质衍生因子-1(SDF-1)与CXCR4(Gαi蛋白偶联的七跨膜趋化因子受体)轴在干细胞对骨髓的定植过程中起主要作用。到妊娠中期第二个月末,骨髓开始被造血干细胞(HSC)定植,造血干细胞以CXCR4-SDF-1依赖的方式从胎儿肝脏被化学吸引而来。CXCR4在造血干细胞上表达,而SDF-1由骨髓基质和成骨细胞分泌,成骨细胞排列在骨髓腔壁上。越来越多的证据表明,骨髓中还含有罕见的CXCR4(+)多能干细胞(PSC)。最近,我们团队在小鼠骨髓和人脐带血中鉴定出了一群CXCR4(+)的非常小的类胚胎干细胞。我们推测,这些细胞在发育过程中作为循环多能干细胞的流动库沉积在骨髓中,在出生后非造血组织和造血组织的组织更新中起关键作用。