Endothelial Progenitor Cells in Diabetes and Renal Failure

描述（由申请人提供）：糖尿病高血糖导致肾损伤，最终可能导致终末期肾病（ESRD），这是慢性肾病最严重的阶段。ESRD患者必须依靠频繁的血液透析治疗来延长生命。一些ESRD患者需要通过手术将合成动静脉移植物插入静脉以建立血管通路。然而，移植物中的最终血栓形成导致患者发病率和住院率增加，沿着需要移植物置换。提高动静脉移植物寿命的一种新的治疗策略是开发一种生物工程移植物，该移植物包括功能性内皮以自然地延迟血栓形成。循环内皮祖细胞（EPC）是最近鉴定的细胞群体，其正在被研究用于开发基于细胞的治疗剂以改善心血管健康。自体内皮祖细胞可能是一个理想的来源，获得内皮细胞的生物工程动静脉移植。为了确定基于自体EPC的治疗对糖尿病ESRD患者的适用性，将研究患者和年龄匹配对照的EPC的血管功能。外周血将从人类志愿者中获得，并将在体外培养以获得内皮细胞（pbEC）。流式细胞术和免疫荧光将用于确认pbEC表型。为了评估pbEC的血管功能，将对来自患者和对照组的pbEC的抗血栓形成、抗凝和炎症活性进行定量，并在新型生物材料上进行比较。最后，将在患者组和对照组之间比较接种到新型生物工程移植物上的pbEC的保留。这些实验旨在提供初步数据，以确定自体pbEC在开发用于血液透析通路的新型生物工程动静脉移植物中的适用性。 公共卫生相关性：目前的药物和手术治疗在改善需要小直径血管置换、修复受损血管或心脏或形成新血管的患者的生活质量方面的潜力有限。相比之下，使用从血液中分离的内皮祖细胞（EPCs）可以通过提供天然血管的活性成分来显著改善这些患者的临床结果。在目前的研究中，将检查来自糖尿病和肾衰竭患者的EPCs，以确定它们是否适合这种基于细胞的治疗。

DESCRIPTION (provided by applicant): Hyperglycemia in diabetes leads to kidney damage that may ultimately culminate in end stage renal disease (ESRD), the most severe stage of chronic kidney disease. ESRD patients must rely on frequent hemodialysis treatments to extend life. Some ESRD patients require surgical insertion of a synthetic arteriovenous graft into a vein for vascular access. However, eventual thrombosis in the graft leads to increased morbidity and hospitalization for patients along with a need for graft replacement. A novel therapeutic strategy to improve the longevity of an arteriovenous graft is the development of a bioengineered graft that includes a functional endothelium to naturally retard thrombosis. Circulating endothelial progenitor cells (EPCs) are a recently identified population of cells that are being investigated for the development of cell-based therapeutics to improve cardiovascular health. Autologous EPCs may be an ideal source by which to obtain endothelial cells for a bioengineered arteriovenous graft. To determine the suitability of autologous EPC-based therapies for diabetic, ESRD patients, the vascular functions of EPCs from patients and age-matched controls will be investigated. Peripheral blood will be obtained from human volunteers and will be cultured in vitro to obtain endothelial cells (pbECs). Flow cytometry and immunofluorescence will be used to confirm the pbEC phenotype. To assess the vascular functionality of pbECs, the anti-thrombogenic, anticoagulant, and inflammatory activities of pbECs derived from patient and control groups will be quantified and compared on a novel biomaterial. Finally, the retention of pbECs seeded onto a novel bioengineered graft will be compared between patient and control groups. These experiments are designed to provide preliminary data to determine the suitability of autologous pbECs in the development of a novel, bioengineered arteriovenous graft for hemodialysis access. PUBLIC HEALTH RELEVANCE: Current pharmacologic and surgical treatments have limited potential for improving the quality of life for patients in need of small diameter blood vessel replacements, repair of damaged blood vessels or heart, or the formation of new blood vessels. In contrast, the use of endothelial progenitor cells (EPCs) isolated from blood may significantly improve the clinical outcome of these patients by providing a living component of native blood vessels. In the current investigation, EPCs from patients with diabetes and kidney failure will be examined to determine their suitability for such cell based-therapies.