Dysfunction and Therapeutic Potential of Endothelial Progenitor Cells in Diabetes Mellitus

Abstract

Diabetes mellitus (DM) is a chronic, multifactorial metabolic disease whereby insulin deficiency or resistance results in hyperglycemia. Endothelial cells (ECs) form the innermost layer of the blood vessel and produce and release a variety of vasoactive substances and growth factors to regulate vascular homeostasis and angiogenesis. Hyperglycemia and insulin resistance can cause endothelial dysfunction, leading to vascular complications such as coronary artery disease, peripheral arterial disease, diabetic nephropathy, neuropathy and retinopathy. The detrimental effect exerted on ECs by hyperglycemia and insulin resistance underlines the importance of reparatory mechanisms in DM. Endothelial progenitor cells (EPCs), derived from bone marrow, have been recognized as endogenous cells involved in endothelial repair and new blood vessel formation. Initially isolated from a subset of circulating CD34+ mononuclear cells, EPCs were found to possess the ability to differentiate into ECs when cultured in vitro and incorporate into newly formed vessels upon transplantation in animal models of ischemia. Due to the low frequency of CD34+ cells in circulation, the vast majority of studies investigating EPC actions have used cells that are generated through the culture of peripheral blood mononuclear cells (PBMNCs) for 4 - 7 days in endothelial selective medium. These cells, mainly of myeloid hematopoietic cell origin, were termed “Early EPCs,” of which, few expressed stem/progenitor-cell markers. Therefore, early EPCs were also termed “myeloid angiogenic cells” (MACs). When PBMNCs are cultured for over 2 weeks, early EPCs gradually diminish while so-called late EPCs appear. Late EPCs share phenotypic features with mature ECs and are therefore also termed blood-derived ECs; they will not be addressed in this review. MAC dysfunction has been observed in a variety of disease conditions including DM. In this article we review the activities and therapeutic potential of MACs in DM. We will interchangeably use “EPCs” and “MACs” to refer to the cells procured by culture of PBMNCs in EC selective medium for approximately 7 days.

Upregulating CXCR7 Accelerates Endothelial Progenitor Cells Mediated Endothelial Reparation via Activating Akt/Keap-1/Nrf2 Signaling in Diabetes Mellitus

“…However, the number of relevant studies revealing the association between EPCs dysfunction and CXCR7 expression in DM was still inadequate. Similar to previous studies [11,12,30], the present study also showed that the functional activity of EPCs derived from rats with diabetes was impaired signi cantly compared with that of EPCs from normal rats. Furthermore.…”

“…Many studies showed that DM impaired EPCs cellular functions in humans and mice [29,30]. Some important molecules, such as CXCR4, NO, and p66Shc, have been identi ed as responsible for the dysfunction of cultured and circulating putative EPCs [11].…”

Serum and Urinary Selenium Status in Patients with the Pre-diabetes and Diabetes in Northeast China

“…China ranks number one, with the highest number of people with diabetes [1]. Both types of DM can cause microvascular complications, e.g., diabetic nephropathy (DN), peripheral neuropathy (DPN), and retinopathy (DR) [2].…”

Upregulating CXCR7 accelerates endothelial progenitor cell-mediated endothelial repair by activating Akt/Keap-1/Nrf2 signaling in diabetes mellitus

“…Many studies have shown that DM impairs EPC functions in humans and mice [ 34 , 35 ]. Specific important molecules, such as CXCR4, NO, and p66Shc, have been identified to control the dysfunction of cultured and circulating putative EPCs [ 11 ].…”