Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model.
Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model.
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DOI：
10.1016/j.jcyt.2013.05.004
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发表时间：
2013-09
期刊：
影响因子：
4.5
通讯作者：
Yellowley CE
中科院分区：
文献类型：
--
作者：
Toupadakis CA;Granick JL;Sagy M;Wong A;Ghassemi E;Chung DJ;Borjesson DL;Yellowley CE
将骨髓源性干细胞和祖细胞递送至损伤部位是促进骨愈合的有效策略。另一种方法是动员内源性异质性干细胞，使其回到损伤部位。AMD 3100是趋化因子受体4（CXCR 4）的拮抗剂，可快速动员干细胞群进入外周血。我们的假设是，使用AMD 3100增加干细胞和祖细胞的循环数量将改善骨折愈合。在C57 BL/6小鼠中诱导横向股骨骨折，之后皮下注射AMD 3100或生理盐水对照3天。注射和/或骨折后24小时，通过流式细胞术、自动血液学分析和细胞培养评估外周血和骨髓中的间充质干细胞（MSC）、造血干细胞和祖细胞（HSPC）以及内皮祖细胞（EPCs）。通过组织形态计量学和µCT评估骨折后84天的愈合情况。AMD 3100注射导致循环MSC、HSC和EPC数量增加。µCT数据表明，第21天时骨折骨痂明显大于生理盐水对照组，第84天时骨痂明显较小（重塑）。在第84天，AMD 3100给药小鼠的骨矿物质密度显著高于生理盐水给药小鼠。我们的数据表明，早期细胞动员对整个再生过程的愈合具有显着的积极影响。内源性干细胞的快速动员可以提供一种有效的替代策略，以促进组织再生的细胞移植。
Delivery of bone marrow derived stem and progenitor cells to the site of injury is an effective strategy to enhance bone healing. An alternate approach is to mobilize endogenous, heterogeneous stem cells that will home to the site of injury. AMD3100 is an antagonist of the chemokine receptor 4 (CXCR4) that rapidly mobilizes stem cell populations into peripheral blood. Our hypothesis was that increasing circulating numbers of stem and progenitor cells using AMD3100 will improve bone fracture healing. A transverse femoral fracture was induced in C57BL/6 mice, after which they were subcutaneously injected for 3 days with AMD3100 or saline control. Mesenchymal stem cells (MSCs), hematopoietic stem and progenitor cells (HSPCs), and endothelial progenitor cells (EPCs) in the peripheral blood and bone marrow were evaluated via flow cytometry, automated hematology analysis, and cell culture 24 hours after injection and/or fracture. Healing was assessed up to 84 days after fracture by histomorphometry and µCT. AMD3100 injection resulted in higher numbers of circulating MSCs, HSCs, and EPCs. µCT data demonstrated that the fracture callus was significantly larger compared to the saline controls at day 21 and significantly smaller (remodeled) at day 84. AMD3100-treated mice have a significantly higher bone mineral density than saline-treated counterparts at day 84. Our data demonstrate that early cell mobilization had significant positive effects on healing throughout the regenerative process. Rapid mobilization of endogenous stem cells could provide an effective alternative strategy to cell transplantation for enhancing tissue regeneration.
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影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
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Isner, JM
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64.5
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120.1
作者：
De Clercq, E
通讯作者：
De Clercq, E