Cross talk with hematopoietic cells regulates the endothelial progenitor cell differentiation of CD34 positive cells.

Cross talk with hematopoietic cells regulates the endothelial progenitor cell differentiation of CD34 positive cells.
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DOI:
10.1371/journal.pone.0106310
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Asahara T
Asahara T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kwon SM;Lee JH;Lee SH;Jung SY;Kim DY;Kang SH;Yoo SY;Hong JK;Park JH;Kim JH;Kim SW;Kim YJ;Lee SJ;Kim HG;Asahara T

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尽管内皮祖细胞在血管再生中起着至关重要的作用,但它与造血细胞之间的具体相互作用仍不清楚。在内皮祖细胞集落形成实验中,我们首次证实了CD34+和CD34−细胞共培养时内皮祖细胞集落的形成显著增加,并确定了适合梭形内皮祖细胞分化的CD34+细胞和CD34−细胞的最佳浓度。在功能上,CD34+和CD34CD34+细胞共培养比单独培养−细胞的黏附、管状形成和迁移能力显著增强。此外,在小鼠后肢缺血模型中,CD34+和CD34CD34−细胞共培养可显著促进血流恢复和毛细血管形成。为了进一步阐明造血细胞在EPC分化中的作用,我们分离了不同群体的造血细胞。T淋巴细胞(CD3+)显著促进CD34+细胞的早期EPC状态,而巨噬细胞(CD11b+)或巨核细胞(CD41+)特异性地促进大的EPC集落。我们的结果提示,特定的造血细胞群在CD34+细胞的EPC分化中起作用,这一发现可能有助于开发一种新的细胞治疗策略,以克服EPC治疗的数量和质量限制。
Despite the crucial role of endothelial progenitor cells (EPCs) in vascular regeneration, the specific interactions between EPCs and hematopoietic cells remain unclear. In EPC colony forming assays, we first demonstrated that the formation of EPC colonies was drastically increased in the coculture of CD34+ and CD34− cells, and determined the optimal concentrations of CD34+ cells and CD34− cells for spindle-shaped EPC differentiation. Functionally, the coculture of CD34+ and CD34− cells resulted in a significant enhancement of adhesion, tube formation, and migration capacity compared with culture of CD34+ cells alone. Furthermore, blood flow recovery and capillary formation were remarkably increased by the coculture of CD34+ and CD34− cells in a murine hind-limb ischemia model. To elucidate further the role of hematopoietic cells in EPC differentiation, we isolated different populations of hematopoietic cells. T lymphocytes (CD3+) markedly accelerated the early EPC status of CD34+ cells, while macrophages (CD11b+) or megakaryocytes (CD41+) specifically promoted large EPC colonies. Our results suggest that specific populations of hematopoietic cells play a role in the EPC differentiation of CD34+ cells, a finding that may aid in the development of a novel cell therapy strategy to overcome the quantitative and qualitative limitations of EPC therapy.
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