Prognostic Significance of Circulating and Endothelial Progenitor Cell Markers in Type 2 Diabetic Foot

Abstract

Objective. We studied circulating precursor cells (CPC) in type 2 diabetes mellitus (T2DM) with neuropathic foot lesions with or without critical limb ischemia and relationships between endothelial precursor cells (EPC) and peripheral neuropathy. Methods and Subjects. We measured peripheral blood CD34, CD133, and CD45 markers for CPC and KDR, CD31 markers for EPC by citofluorimetry and systemic neural nociceptor CGRP (calcitonin gene related protein) by ELISA in 8 healthy controls (C) and 62 T2DM patients: 14 with neuropathy (N), 20 with neuropathic foot lesions (N1), and 28 with neuroischemic recent revascularized (N2) foot lesions. Timing of lesions was: acute (until 6 weeks), healed, and not healed. Results. CD34+ and CD133+ were reduced in N, N1, and N2 versus C, and CD34+ were lower in N2 versus N1 (P = 0.03). In N2 CD34+KDR+ remain elevated in healed versus chronic lesions and, in N1 CD133+31+ were elevated in acute lesions. CGRP was reduced in N2 and N1 versus C (P < 0.04 versus C 26 ± 2 pg/mL). CD34+KDR+ correlated in N2 with oximetry and negatively in N1 with CGRP. Conclusions. CD34+ CPC are reduced in diabetes with advanced complications and diabetic foot. CD34+KDR+ and CD31+133+ EPC differentiation could have a prognostic and therapeutic significance in the healing process of neuropathic and neuroischemic lesions.

Electrical Muscle Stimulation Induces an Increase of VEGFR2 on Circulating Hematopoietic Stem Cells in Patients With Diabetes

“…[7][8][9][10][11][12] The lower frequency of HSCs in persons with diabetes has been associated with a higher risk of progress and severity of diabetic vascular complications, including DN 8,13,14 and diabetic foot wounds. [15][16][17][18] Different types of HSCs have been used to successfully treat diabetic animal models of DN. [19][20][21][22][23] HSCs can differentiate into hepatocytes, epithelial cells, 24 cardiomyocytes, smooth muscle cells, or endothelial cells.…”

Circulating angiogenic stem cells in type 2 diabetes are associated with glycemic control and endothelial dysfunction

“…Additional causality and mechanistic studies are needed to more clearly define the relationship between CACs and diabetes in humans. Nevertheless, indications from prior human and animal studies are consistent with the idea that attenuated vascular repair due to low levels of pro-angiogenic cells, or dysfunctional pro-angiogenic cells promotes endothelial dysfunction and pathological outcomes such as retinopathy [ 29 ], neuropathy [ 11 , 35 ], and nephropathy [ 10 , 36 ].…”

Cell recruitment by amnion chorion grafts promotes neovascularization

“…CD34 is a well-described marker for HPCs, predicting enhanced cellular function and improved therapeutic potential [33–35]. Immunohistochemistry demonstrated that dHACM stimulated a significant increase in CD34 + progenitor cells in the peri- implant space and surrounding skin compared with both sham surgical sites and healthy skin (4-fold, day 14; 3-fold, day 28; P ≤ 0.05) and control ADM (2-fold, day 14; 3-fold, day 28; P ≤ 0.05) (Fig.…”