Khoo Cheen Peen, Valorani M G, Brittan Mairi, Alison Malcolm R, Warnes Gary, Johansson Ulrika, Hawa Mohammed, Pozzilli Paolo
Queen Mary's School of Medicine and Dentistry of London, Centre for Diabetes and Metabolic Medicine, London, UK.
Diabetes Metab Res Rev. 2009 Jan;25(1):89-93. doi: 10.1002/dmrr.898.
Endothelial progenitor cells (EPCs) in bone marrow (BM) and peripheral blood (PB) contribute to tissue repair in various pathological conditions via the formation of new blood vessels. Previous studies indicate that diabetic patients have reduced EPC number and deregulated EPC function, although the regenerative properties of EPCs in diabetes are unknown. We wish to characterize and compare EPCs from pre-diabetic and diabetic non-obese diabetic (NOD) mice, a model of type 1 diabetes (T1D), in order to delineate the role of these cells in the pathogenesis of autoimmune diabetes.
Whole BM was obtained by flushing femurs, tibias and illiac crests from pre-diabetic and diabetic NOD mice (5-30 weeks) in which the diabetic status was confirmed by measuring blood glucose levels (> or =11.5 mmol/L); PB was collected in heparin-coated tubes and lysed after incubation with antibodies directed against EPCs.
FACS analyses revealed a significant decrease in EPC number (CD31(+), c-Kit(+), Sca-1(+), Lin(-)) in BM from diabetic compared to pre-diabetic mice (P = 0.02). Conversely, EPC number was significantly increased in PB from diabetic compared to pre-diabetic mice (P = 0.01).
These data suggest that at the onset of diabetes, BM-derived EPCs are stimulated to enter the systemic circulation likely in response to signals from the pancreas. Further studies are required to elucidate whether EPCs home the damaged pancreas, thus representing a prospective source of autologous cells for beta-cell regeneration therapy.
骨髓（BM）和外周血（PB）中的内皮祖细胞（EPCs）通过形成新血管，在各种病理状态下有助于组织修复。先前的研究表明，糖尿病患者的EPC数量减少且功能失调，尽管糖尿病中EPC的再生特性尚不清楚。我们希望对来自糖尿病前期和糖尿病非肥胖糖尿病（NOD）小鼠（1型糖尿病（T1D）模型）的EPC进行表征和比较，以阐明这些细胞在自身免疫性糖尿病发病机制中的作用。
通过冲洗糖尿病前期和糖尿病NOD小鼠（5 - 30周）的股骨、胫骨和髂嵴获得全骨髓，通过测量血糖水平（≥11.5 mmol/L）确认糖尿病状态；将外周血收集于肝素包被的试管中，与针对EPC的抗体孵育后裂解。
流式细胞术分析显示，与糖尿病前期小鼠相比，糖尿病小鼠骨髓中EPC数量（CD31(+)、c-Kit(+)、Sca-1(+)、Lin(-)）显著减少（P = 0.02）。相反，与糖尿病前期小鼠相比，糖尿病小鼠外周血中EPC数量显著增加（P = 0.01）。
这些数据表明，在糖尿病发病时，骨髓来源的EPC可能响应来自胰腺的信号而被刺激进入体循环。需要进一步研究以阐明EPC是否归巢至受损胰腺，从而代表β细胞再生治疗的自体细胞潜在来源。
