Demonstration of the presence of independent pre-osteoblastic and pre-adipocytic cell populations in bone marrow-derived mesenchymal stem cells
Demonstration of the presence of independent pre-osteoblastic and pre-adipocytic cell populations in bone marrow-derived mesenchymal stem cells
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DOI：
10.1016/j.bone.2008.03.011
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发表时间：
2008-07-01
期刊：
影响因子：
4.1
通讯作者：
Kassem, M.
中科院分区：
文献类型：
--
作者：
Post, S.;Abdallah, B. M.;Kassem, M.
间充质干细胞（MSC）被定义为可塑贴壁的克隆细胞，是成骨细胞和脂肪细胞的常见祖细胞。在一些临床条件下，已经观察到骨和脂肪之间的反比关系，并认为这是由将MSC分化重定向到一个特定的谱系引起的。然而，骨和脂肪之间的这种反向关系并不一致，在某些体内条件下，骨和脂肪可以独立变化，这表明不同的前体细胞群。为了验证这一假设，我们广泛表征了来自小鼠骨髓的两种塑料贴壁克隆MSC系（mMSC1和mMSC2）。这两种细胞系在培养中很容易生长，并经历了100多次种群倍增，其生长速度没有明显差异。两种细胞系均对小鼠MSC标记物Sca-1呈阳性，mMSC1也对CD13呈阳性。两种细胞系均接受体外培养诱导成骨和脂肪生成。mMSC1和非mMSC2仅能分化为脂肪细胞，这可以通过脂肪细胞标志物（aP2、脂联素、脂素、PPAR γ 2和C/EBPa）的表达和油红0染色显示的成熟脂肪细胞的存在来证明。另一方面，mMSC2和非mMSC1分化成成骨细胞谱系，通过上调成骨细胞制造因子（CBFA1/RUNX2, Osterix，碱性磷酸酶，骨唾液蛋白和骨桥蛋白）和形成茜素红染色矿化基质。与体外实验结果一致，mMSC2而非mMSC1在免疫缺陷（NOD/SCID）小鼠皮下植入后能够在体内形成骨。我们的数据表明，与目前的观点相反，骨髓中含有克隆亚群的细胞，这些细胞致力于成骨细胞或脂肪细胞谱系。这些细胞群可能在衰老和骨病中经历独立的变化，因此是治疗的重要目标。(C) 2008年Elsevier Inc.出版
Mesenchymal stem cells (MSC) are defined as plastic-adherent, clonal cells that are common progenitors for osteoblasts and adipocytes. An inverse relationship between bone and fat has been observed in several clinical conditions and has been suggested to be caused by re-directing MSC differentiation into one particular lineage. However, this inverse relationship between bone and fat is not consistent and under certain in vivo conditions, bone and fat can change independently suggesting separate precursor cell populations. In order to test for this hypothesis, we extensively characterized two plastic-adherent clonal MSC lines (mMSC1 and mMSC2) derived from murine bone marrow. The two cell lines grew readily in culture and have undergone more than 100 population doublings with no apparent differences in their growth rates. Both cell lines were positive for the murine MSC marker Sca-1 and mMSC1 was also positive for CD13. Both cell lines were exposed to in vitro culture induction of osteogenesis and adipogenesis. mMSC1 and not mMSC2 were only able to differentiate to adipocytes evidenced by the expression of adipocyte markers (aP2, adiponectin, adipsin, PPAR gamma 2 and C/EBPa) and the presence of mature adipocytes visualized by Oil Red 0 staining. On the other hand, mMSC2 and not mMSC1 differentiated to osteoblast lineage as demonstrated by up-regulation of osteoblastic makers (CBFA1/RUNX2, Osterix, alkaline phosphatase, bone sialoprotein and osteopontin) and formation of alizarin red stained mineralized matrix in vitro. Consistent with the in vitro results, mMSC2 and not mMSC1, were able to form bone in vivo after subcutaneous implantation in immune-deficient (NOD/SCID) mice. Our data suggest that contrary to the current belief, bone marrow contains clonal subpopulations of cells that are committed to either osteoblast or adipocyte lineage. These cell populations may undergo independent changes during aging and in bone diseases and thus represent important targets for therapy. (C) 2008 Published by Elsevier Inc.