Diabetes impairs endothelial progenitor cell-mediated blood vessel formation in response to hypoxia
Diabetes impairs endothelial progenitor cell-mediated blood vessel formation in response to hypoxia
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DOI：
10.1097/01.prs.0000244830.16906.3f
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发表时间：
2007-01-01
影响因子：
3.6
通讯作者：
Gurtner, Geoffrey C.
中科院分区：
文献类型：
--
作者：
Capla, Jennifer M.;Grogan, Raymon H.;Gurtner, Geoffrey C.
背景：糖尿病患者患有血管功能障碍，因组织缺血反应能力受损而导致冠状动脉疾病和外周血管疾病的风险增加。由于已知内皮祖细胞归巢于缺血部位并参与新血管生长，因此作者检查了糖尿病对缺氧条件下的人内皮祖细胞功能和外周组织信号传导的影响，并确定这些细胞是否可能成为治疗糖尿病血管并发症的有用的细胞疗法。方法：循环来自 2 型糖尿病患者和对照的人内皮祖细胞 分离并进行体外粘附、迁移和增殖测定（n = 5）。在糖尿病和非糖尿病环境中对细胞动员和募集进行了体内研究（n = 6）。在小鼠缺血模型（n = 6）中分析了外源性人类糖尿病细胞和正常细胞的治疗效果。结果：与对照相比，人类糖尿病内皮祖细胞响应缺氧的粘附、迁移和增殖显着降低。在糖尿病小鼠中，与对照组相比，骨髓中的细胞动员和招募到缺血组织中的细胞显着减少。作为糖尿病小鼠的替代疗法，全身注射的正常细胞增加，但并未使缺血组织存活正常化。结论：这些发现表明，糖尿病会导致内皮祖细胞和外周组织对缺氧的反应出现缺陷。内皮祖细胞功能和信号传导的这些变化为 2 型糖尿病患者缺血事件后临床结果不佳提供了新的解释。基于这些发现，基于内皮祖细胞的细胞疗法不太可能能够预防糖尿病并发症。
Background: Diabetics suffer from vascular dysfunction with increased risks of coronary artery disease and peripheral vascular disease secondary to an impaired ability to respond to tissue ischemia. Because endothelial progenitor cells are known to home to sites of ischemia and participate in new blood vessel growth, the authors examined the effects of diabetes on human endothelial progenitor cell function and peripheral tissue signaling in hypoxia, and determined whether these cells might be a useful cell-based therapy for diabetic vascular complications.Methods: Circulating human endothelial progenitor cells from type 2 diabetic patients and controls were isolated and subjected to in vitro adhesion, migration, and proliferation assays (n = 5). Cell mobilization and recruitment were studied in vivo in diabetic and nondiabetic environments (n = 6). Exogenous human diabetic and normal cells were analyzed for therapeutic efficacy in a murine ischemia model (n = 6).Results: Adhesion, migration, and proliferation of human diabetic endothelial progenitor cells in response to hypoxia was significantly reduced compared with controls. In diabetic mice, cell mobilization from the bone marrow and recruitment into ischemic tissue was significantly reduced compared with controls. Normal cells injected systemically as replacement therapy in a diabetic mouse increased but did not normalize ischemic tissue survival.Conclusions: These findings suggest that diabetes causes defects in both the endothelial progenitor cell and peripheral tissue responses to hypoxia. These changes in endothelial progenitor cell function and signaling offer a novel explanation for the poor clinical outcome of type 2 diabetics following ischemic events. Based on these findings, it is unlikely that endothelial progenitor cell-based cellular therapies will be able to prevent diabetic complications.