1 骨髓间充质干细胞的发现和来源 骨髓组织中有多种细胞成分，除基质细胞等已经分化的细胞外，还含有两类多潜能干细胞：造血干细胞和间充质干细胞。1987年Friedenstein等发现在塑料培养皿中培养的贴壁的骨髓单个细胞在一定条件下可分化为多种类型的细胞，而且经过20－30个培养周期仍能保持其多向分化潜能。由于骨髓中的这种多能细胞能够分化为多种中胚层来源的间质细胞,故称之为间充质干细胞(Mesenchymalstemcells，MSCs),或间质祖细胞(MPCs)，是成人多能干细胞的一类。早期分离培养时，发现其形状呈成纤维细胞样而称其为成纤维细胞集落形成单位(Colony-formingunit-fibroblast，CFU-F)，或骨髓基质成纤维细胞(Marrowstromalfibroblast，MSF)。FriedensteinAJ,ChailakhyanRK,GerasimovUV.Bonemarrowosteogenicstemcells:invitrocultivationandtransplantationindiffusionchambers.CellTissueKinet,1987,20(3):263-267] 2 鉴于其强大的增殖能力及多向分化潜能，可在体外长期培养和遗传背景较稳定，而且用自体干细胞诱导构建的组织不涉及伦理问题，也不存在MHC限制，所以骨髓间充质干细胞日益受到重视。但是与造血干细胞等其他细胞相比，骨髓中MSCs的数量非常少，约占整个骨髓有核细胞的十万分之一，并随年龄的增加，细胞数量逐渐减少。因此，如何简便有效地从骨髓中获取高纯度的MSCs显得尤为重要，寻找高度特异性的MSCs的表面抗原也就成为MSCs研究中的一项重要任务和目标。 不仅如此，一种同样来源于骨髓、贴壁生长、被认为更原始（可以分化为MSCs）也具有更强增殖能力的干细胞也被鉴定，它就是多能成体祖细胞（multipotentadultProgenitorcell(MAPC)ormesodermalprogenitorcell(MPC)）[Reyes,M.,Lund,T.,Leuvik,T.,Aguiar,D.,Koodie,L.,Verfaillie, C.M.(2001)Purificationandinvivoexpansionofpostnatalhumanmarrowmesodermalprogenitorcells.Blood98,2615-2625]，因能和MSCs一起被纯化而统称BMstromalstemcell。 3利用流式细胞仪的研究显示,MSCs属混杂细胞群，其表面抗原也具有非专一性,它表达了间质细胞、内皮细胞和表皮细胞的表面标志。主要包括:①黏附分子,如CD166、CD54、CD102、CD44、CD106等。②生长因子和细胞因子受体,如白介素21受体(IL-1R)、IL-3R、IL-4R、IL-6R、IL-7R、C干扰素受体(IFN-CR)、肿瘤坏死因子(TNF)-A等。③整合素家族成员,包括CD49a、CD49b、CD49c、CD29、CD104等。④其他如CD90、CD105等。不表达造血细胞的表面标志,如CD34、CD45、CD14、CD3、CD4、CD8等,也不表达与人白细胞抗原(HLA)识别有关的共刺激分子及主要组织相容性复合物类分子如HLA-DR抗原等。 但到目前为止,对于MSC的表面标志尚不完全确定，有些标志尚存在种属特异性，现将普遍认同的不同种属的MSCs的表面抗原情况综述如下： 表一：MSCs的表面抗原 HUMAN RAT MOUSE REFERENCE SH2+andSH3+ CaplanAI.Mesenchymalstemcells.J.Orthop.Res.1991;9:641-650. 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