Endothelial progenitor cell dysfunction in patients with progressive chronic kidney disease

Abstract

Endothelial progenitor cells (EPC) contribute to repair and maintenance of the vascular system, but in patients with chronic kidney disease (CKD), the number and function of EPC may be affected by kidney dysfunction. We assessed numbers and the angiogenic function of EPC from patients with CKD in relation to disease progression. In a cross-sectional, prospective study, 50 patients with varying degrees of CKD, including 20 patients undergoing dialysis and 10 healthy controls, were included. Mononuclear cells were isolated, and circulating EPC were quantified by flow cytometry based on expression of CD14 and CD34. EPC were cultured on fibronectin-coated supramolecular films of oligocaprolactone under angiogenic conditions to determine their angiogenic capacity and future use in regenerative medicine. CKD patients had normal numbers of circulating CD14+ EPC but reduced numbers of circulating CD34+ EPC. Furthermore, EPC from patients with CKD displayed functional impairments, i.e., hampered adherence, reduced endothelial outgrowth potential, and reduced antithrombogenic function. These impairments were already observed at stage 1 CKD and became more apparent when CKD progressed. Dialysis treatment only partially ameliorated EPC impairments in patients with CKD. In conclusion, EPC number and function decrease with advancing CKD, which may hamper physiological vascular repair and can add to the increased risk for cardiovascular diseases observed in CKD patients.

Progenitor cells and vascular function are impaired in patients with chronic kidney disease

“…No EPC or SPC outgrowth numbers were reported in this study. Krenning et al [16] reported lower numbers of CD34 + -haematopoietic stem cells in CKD patients more comparable to our population, but did not assess CD34 + KDR + -EPC levels, the type of EPC that was predictive for cardiovascular events in CAD patients [29]. They observed decreased endothelial outgrowth of MNC obtained from CKD patients on PCLdiUPy biomaterial and suggested a limitation for use of EPC derived from CKD patients in regenerative medicine.…”

Dysfunctional Endothelial Progenitor Cells in Chronic Kidney Disease

“…85 Evidence of EPC dysfunction in CKD continues to accrue. 86,87 It is an urgent task for future studies to characterize the mechanisms of EPC dysfunction and design rational therapeutic strategies to restore their competence.…”

Transplantation of bone marrow-derived endothelial progenitor cells attenuates myocardial interstitial fibrosis and cardiac dysfunction in streptozotocin-induced diabetic rats

“…Since their revolutionary discovery by Asahara et al (6) in 1997, EPCs have been demonstrated to be of importance in postnatal vasculogenesis through pivotal bioactivities, mobilization, homing, migration, differentiation and proliferation in angiovasculogenic tissues (7). However, decreased levels of circulating EPCs have been reported in a wide range of pathological conditions, such as chronic kidney disease (8), hypercholesterolemia (9), rheumatoid arthritis (10), obesity (11) and coronary artery disease (12). Furthermore, an altered status of circulating EPCs represents a diagnostic biomarker for endothelial dysfunction and individual diseases.…”