Molecular Trafficking Mechanisms of Multipotent Mesenchymal Stem Cells Derived from Human Bone Marrow and Placenta
Molecular Trafficking Mechanisms of Multipotent Mesenchymal Stem Cells Derived from Human Bone Marrow and Placenta
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DOI：
10.1089/scd.2007.0156
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发表时间：
2008-10-01
影响因子：
4
通讯作者：
Atkinson, Kerry
中科院分区：
文献类型：
--
作者：
Brooke, Gary;Tong, Hui;Atkinson, Kerry
我们比较了人（h）来源于骨髓（bm）或胎盘（p）的多能间充质干细胞（MSC）的潜在运输机制。hbmMSC和hpMSC均表达广泛的细胞表面粘附分子，包括β 1-整联蛋白（CD 29）和CD 44。阵列数据显示hbmMSC和hpMSC均表达细胞粘附分子CD 54（ICAM-1）、E-钙粘蛋白、CD 166（ALCAM）、CD 56（NCAM）、CD 106（VCAM-1）、CD 49 a、B、c、e和f（整合素α 1、2、3、4和6）、整合素α 11、CD 51（整合素α V）和CD 29（整合素β 1）的mRNA。使用重组嵌合构建体证明hpMSC而不是hbmMSC与VCAM-1的功能性结合。骨髓和胎盘MSC都不表达内皮选择素的配体，如PSGL-1或唾液酸刘易斯X（sLe（x））碳水化合物，也都不能与内皮选择素CD 62 E（E-选择素）和CD 62 P（P-选择素）的嵌合构建体功能性结合。此外，MSC表达了有限范围的转移酶表达sLex所必需的，没有检测到岩藻糖基转移酶IV或VII的表达。胎盘MSC表达趋化因子受体CCR 1和CCR 3的mRNA，而hbmMSC不表达，hbmMSC和hpMSC均表达CCR 7、CCR 8、CCR 10、CCR 11、CXCR 4和CXCR 6的mRNA。在hbmMSC和hpMSC中检测到细胞内趋化因子受体蛋白CCR 1、CCR 3、CXCR 3、CXCR 4和CXCR 6的表达。趋化因子受体的细胞表面表达受到更多限制，只有CXCR 6在hbmMSC和hpMSC上显示出强信号。虽然未检测到CXCR 4的细胞表面表达，但MSC对其配体CXCL 12（SDF-1）作出反应而迁移。因此，hbmMSC和hpMSC在mRNA和蛋白质水平上对细胞表面粘附和趋化因子受体分子具有几乎相同的谱。然而，在功能水平上，hpMSC可能以比hbmMSC更上级的方式利用VLA-4介导的结合，因此可能具有比hbmMSC更上级的体内植入特性。
We compared potential trafficking mechanisms used by human (h) multipotent mesenchymal stem cells (MSC) derived from bone marrow (bm) or placenta (p). Both hbmMSC and hpMSC expressed a broad range of cell surface adhesion molecules including beta 1-integrins (CD29) and CD44. Array data showed that both hbmMSC and hpMSC expressed mRNA for the cell adhesion molecules CD54 (ICAM-1), E-cadherin, CD166 (ALCAM), CD56 (NCAM), CD106 (VCAM-1), CD49a, b, c, e and f (integrins alpha 1, 2, 3, 4 and 6), integrin alpha 11, CD51 (integrin alpha V), and CD29 ( integrins beta 1). Functional binding of hpMSC, but not hbmMSC to VCAM-1 was demonstrated using recombinant chimeric constructs. Neither bone marrow nor placental MSC expressed ligands to endothelial selectins such as PSGL-1 or sialyl Lewis X (sLe(x)) carbohydrates and neither were able to bind functionally to chimeric constructs of the endothelial selectins CD62E (E-selectin) and CD62P (P-selectin). Furthermore, MSC expressed a restricted range of transferases necessary for expression of sLex, with no detectable expression of fucosyl transferases IV or VII. Placental MSC, but not hbmMSC, expressed mRNA for the chemokine receptors CCR1 and CCR3, and both hbmMSC and hpMSC expressed mRNA for CCR7, CCR8, CCR10, CCR11, CXCR4 and CXCR6. Intracellular chemokine receptor protein expression of CCR1, CCR3, CXCR3, CXCR4 and CXCR6 was detected in both hbmMSC and hpMSC. Cell surface expression of chemokine receptors was much more restricted with only CXCR6 displaying a strong signal on hbmMSC and hpMSC. Although cell surface expression of CXCR4 was not detected, MSC migrated in response to its ligand, CXCL12 (SDF-1). Thus, hbmMSC and hpMSC have an almost identical profile for cell surface adhesion and chemokine receptor molecules at the mRNA and protein levels. However, at the functional level, hpMSC likely utilise VLA-4-mediated binding in a superior manner to hbmMSC and thus may have superior engraftment properties to hbmMSC in vivo.