Hypoxia Responsive Mesenchymal Stem Cells Derived from Human Umbilical Cord Blood Are Effective for Bone Repair

Hypoxia Responsive Mesenchymal Stem Cells Derived from Human Umbilical Cord Blood Are Effective for Bone Repair
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DOI:
10.1089/scd.2009.0447
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发表时间:
2010-08-01
影响因子:
4
通讯作者:
Ohneda, Osamu
Ohneda, Osamu
中科院分区:
医学3区
文献类型:
--
作者:
Nagano, Masumi;Kimura, Kenichi;Ohneda, Osamu

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间充质干细胞(MSC)由于其多向分化能力而在各种细胞治疗中非常有用。来源于脐带血的MSC通常通过其塑性粘附而不使用特定的细胞表面标记物分离,并回顾性地检查其成骨、成脂和成软骨分化特性。在这里,我们报告2个亚群的间充质干细胞,分离的基础上醛脱氢酶(ALDH)的活性。具有高ALDH活性(Alde-高)的MSC比具有低ALDH活性(Alde-低)的MSC增殖更多。Alde-高的MSC在体外培养中具有比Alde-低的MSC更大的分化能力。Alde-High MSCs移植到骨折的小鼠股骨中能够早期修复组织和快速骨替代。Alde-高MSC也比Alde-低MSC对缺氧更敏感,Flt-1,CXCR 4和Angiopoietin-2上调。因此,具有高ALDH活性的MSC可以作为在短时间内愈合骨折的有效治疗工具。
Mesenchymal stem cells (MSCs) are highly useful in a variety of cell therapies owing to their multipotential differentiation capability. MSCs derived from umbilical cord blood are generally isolated by their plastic adherence without using specific cell surface markers and examined for their osteogenic, adipogenic, and chondrogenic differentiation properties retrospectively. Here, we report 2 subpopulations of MSCs, separated based on aldehyde dehydrogenase (ALDH) activity. MSCs with a high ALDH activity (Alde-High) proliferated more than those with a low ALDH activity (Alde-Low). Alde-High MSCs had a greater ability to differentiate than Alde-Low MSCs in in vitro culture. Transplantation of Alde-High MSCs into fractured mouse femurs enabled early repair of tissues and rapid bone substitution. Alde-High MSCs were also more responsive to hypoxia than Alde-Low MSCs, with the upregulation of Flt-1, CXCR4, and Angiopoietin-2. Thus, MSCs with a high ALDH activity might serve as an effective therapeutic tool for healing fractures within a short period of time.