Zhang Z L, Tong J, Lu R N, Scutt A M, Goltzman D, Miao D S
Calcium Research Laboratory, McGill University Health Centre and Department of Medicine, McGill University, Montreal, Quebec, Canada.
Bone Marrow Transplant. 2009 Jan;43(1):69-81. doi: 10.1038/bmt.2008.260. Epub 2008 Aug 18.
We demonstrated that non-adherent BM cells (NA-BMCs) can be expanded in suspension and give rise to multiple mesenchymal phenotypes including fibroblastic, osteoblastic, chondrocytic and adipocytic as well as glial cell lineages in vitro using the 'pour-off' BMC culture method. Mesenchymal stem cells (MSCs) derived from NA-BMCs (NA-MSCs) from wild-type mice were transplanted into VDR gene knockout (VDR(-/-)) mice that had received a lethal dose of radiation. Results revealed that NA-MSC can be used to rescue lethally irradiated mice and become incorporated into a diverse range of tissues. After lethal dose irradiation, all untransplanted mice died within 2 weeks, whereas those transplanted with NA-MSCs were viable for at least 3 months. Transplantation rescued these mice by reconstructing a hematopoietic system and repairing other damaged tissues. WBC, RBC and platelet counts recovered to normal after 1 month, and VDR gene expression was found in various tissues of viable VDR(-/-) recipients. Adult BM harbors pluripotent NA-MSCs, which can migrate in vivo into multiple body organs. In an appropriate microenvironment, they can adhere, proliferate and differentiate into specialized cells of target tissues and thus function in damaged tissue regeneration and repair.
我们证明,使用“倾倒法”骨髓细胞培养方法,非贴壁骨髓细胞(NA-BMCs)能够在悬浮状态下扩增,并在体外产生多种间充质表型,包括成纤维细胞、成骨细胞、软骨细胞和脂肪细胞以及神经胶质细胞谱系。将来自野生型小鼠的NA-BMCs(NA-MSCs)衍生的间充质干细胞(MSCs)移植到接受致死剂量辐射的维生素D受体基因敲除(VDR(-/-))小鼠体内。结果显示,NA-MSC可用于挽救受到致死剂量辐射的小鼠,并整合到多种组织中。在接受致死剂量辐射后,所有未移植的小鼠在2周内死亡,而移植了NA-MSCs的小鼠至少存活了3个月。移植通过重建造血系统和修复其他受损组织挽救了这些小鼠。1个月后白细胞、红细胞和血小板计数恢复正常,并且在存活的VDR(-/-)受体的各种组织中发现了VDR基因表达。成年骨髓中含有多能性NA-MSCs,它们能够在体内迁移到多个身体器官。在合适的微环境中,它们能够黏附、增殖并分化为靶组织的特化细胞,从而在受损组织的再生和修复中发挥作用。