Sustained stromal stem cell self-renewal and osteoblastic differentiation during aging
Sustained stromal stem cell self-renewal and osteoblastic differentiation during aging
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DOI：
10.1089/rej.2006.9.10
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发表时间：
2006-03-01
影响因子：
2.6
通讯作者：
Schiller, PC
中科院分区：
文献类型：
--
作者：
D'Ippolito, G;Howard, GA;Schiller, PC
我们已经报道了一个独特的人骨髓基质细胞亚群的分离称为骨髓分离的成人多系诱导（迈阿密）细胞。胚胎干细胞标志物SSEA-4、Oct-4、雷克斯-1和端粒酶逆转录酶的表达表明这些细胞的发育不成熟状态。它们类似于原始干细胞，至少在体外能够分化成来自所有三个胚层的成熟样细胞。迈阿密细胞的特征在于独特的分子特征，这将它们与其他骨髓基质细胞群区分开来。尽管在所有骨髓有核细胞中，迈阿密细胞的频率从3岁时的0.01%下降到45岁时的0.0018%，但它们的数量在45岁后保持不变。迈阿密细胞特征性标志物的表达水平保持恒定，与年龄和性别无关。在长期的体外扩增实验中，老化使群体倍增时间增加约30%，而迈阿密细胞向成骨细胞的特异性体外分化不受影响。由于骨髓中的氧张力范围从1%到7%，我们研究了氧张力在调节迈阿密细胞自我更新和在长期培养期间维持其多能性的能力中的作用。低氧张力上调原始胚胎干细胞标志物的mRNA。我们的研究结果表明，在低氧张力下维持体外原始人类细胞的发育更符合生理学，更有利于干细胞。对于成骨细胞分化，需要由连接蛋白43介导的缝隙连接通讯。其抑制作用不仅阻断成骨细胞分化，而且促进脂肪细胞分化。
We have reported the isolation of a unique subpopulation of human stromal cells from bone marrow termed marrow-isolated adult multilineage inducible (MIAMI) cells. The expression of embryonic stem cell markers SSEA-4, Oct-4, Rex-1, and telomerase reverse transcriptase indicates the developmentally immature status of these cells. They resemble primitive stem cells in their capacity to differentiate, at least in vitro, into mature-like cells from all three germ layers. MIAMI cells are characterized by a unique molecular profile that distinguishes them from other marrow stromal cell populations. Although the frequency of MIAMI cells, among all marrow nucleated cells, decreases from 0.01% at age 3 to 0.0018% at age 45, their numbers remain unchanged after age 45. The level of expression of the markers characteristic of MIAMI cells remains constant independent of age and gender. In long-term in vitro expansion experiments aging increased the population doubling time by about 30%, whereas specific in vitro differentiation of MIAMI cells toward osteoblastic cells was unaffected. Because the oxygen tension in bone marrow ranges from 1% to 7%, we examined the role of oxygen tension in regulating the capacity of MIAMI cells to self-renew and maintain their pluripotentiality during long-term culture. Low oxygen tension upregulated mRNAs for primitive embryonic stem cell markers. Our results suggest that maintaining developmentally primitive human cells in vitro at low oxygen tension is more physiologic and favors stemness. For osteoblastic differentiation, gap-junctional communication mediated by connexin43 is required. Its inhibition not only blocked osteoblastic differentiation but stimulated the adipocytic differentiation.