Lund Troy C, Tolar Jakub, Orchard Paul J
Pediatric Hematology-Oncology and Blood and Marrow Transplant Program, University of Minnesota, Mayo Mail Code 484, D-557 Mayo Building, 420 Delaware St. S.E., Minneapolis, MN 55455, USA.
Haematologica. 2008 Jun;93(6):908-12. doi: 10.3324/haematol.12384. Epub 2008 Apr 9.
Bone marrow mesenchymal stem cells are multipotent cells found lining the bone marrow cavity supporting the growth and differentiation of hematologic progenitors. There is growing evidence that these cells can, under the right circumstances, enter the peripheral circulation. We show that granulocyte colony-stimulating factor mobilized peripheral blood contains cells which form colonies and have a similar fibroblastic morphology (termed CFU-F) to bone marrow mesenchymal stem cells. These cells were found at a very low incidence (0.0002%). Mobilized peripheral blood CFU-F were successfully differentiated into osteogenic and adipogenic lineages. FACS analysis showed that the cells had a similar profile to bone marrow mesenchymal stem cells. Importantly, mobilized peripheral blood CFU-F had limited expansion potential and became senescent 20-25 days after isolation. Mobilized peripheral blood CFU-F also did not have any telomerase activity and displayed significant telomere shortening. The rarity of CFU-F in mobilized peripheral blood and the subsequent pressure to divide in cell culture probably contribute to early cellular senescence. Their potential for use in transplant or gene therapy is, therefore, limited.
骨髓间充质干细胞是一种多能细胞,位于骨髓腔内,支持血液祖细胞的生长和分化。越来越多的证据表明,在适当的情况下,这些细胞可以进入外周循环。我们发现,粒细胞集落刺激因子动员的外周血中含有能够形成集落的细胞,其成纤维细胞形态与骨髓间充质干细胞相似(称为CFU-F)。这些细胞的发生率非常低(0.0002%)。动员的外周血CFU-F成功分化为成骨和成脂谱系。流式细胞术分析表明,这些细胞的特征与骨髓间充质干细胞相似。重要的是,动员的外周血CFU-F的增殖潜力有限,分离后20-25天就会衰老。动员的外周血CFU-F也没有任何端粒酶活性,并且端粒明显缩短。动员的外周血中CFU-F的稀少以及细胞培养中随后的分裂压力可能导致细胞早期衰老。因此,它们在移植或基因治疗中的应用潜力有限。