Amelioration of Glucose Control Mobilizes Circulating Pericyte Progenitor Cells in Type 2 Diabetic Patients with Microangiopathy

Abstract

Chronic diabetic complications result from an imbalance between vascular damage and regeneration. Several circulating lineage-committed progenitor cells have been implicated, but no data are available on pericyte progenitor cells (PPCs). Based on the evidence that PPCs increase in cancer patients after chemotherapy, we explored whether circulating PPC levels are affected by glucose control in type 2 diabetic patients, in relation to the presence of chronic complications. We enumerated peripheral blood PPCs as Syto16+CD45−CD31−CD140b+ events by flow cytometry at baseline and after 3 and 6 months of glucose control by means of add-on basal insulin therapy on top of oral agents in 38 poorly controlled type 2 diabetic patients. We found that, in patients with microangiopathy (n = 23), the level of circulating PPCs increased about 2 fold after 3 months and then returned to baseline at 6 months. In patients without microangiopathy (control group, n = 15), PPCs remained fairly stable during the whole study period. No relationship was found between change in PPCs and macroangiopathy (either peripheral, coronary, or cerebrovascular). We conclude that glucose control transiently mobilizes PPCs diabetic patients with microangiopathy. Increase in PPCs may represent a vasoregenerative event or may be a consequence of ameliorated glucose control on microvascular lesions.

Diversified Expression of NG2/CSPG4 Isoforms in Glioblastoma and Human Foetal Brain Identifies Pericyte Subsets

“…These cells, which showed a progenitor-like small size and morphology with a high nucleus/cytoplasm ratio, lacked other markers of leukocytes and endothelial progenitor cells, such as CD3, CD31, CD45, CD146 and CD105, but expressed PDGFRβ that, in our double staining, was co-localized to a small degree with isoforms of NG2/CSPG4 revealed by mAb 2161F9, thus confirming that these NG2/CSPG4-reactive cells show, in part, a pericytic phenotype [ 44 ]. An increased frequency of PPCs was found in patients and mice with malignant tumours and in type 2 diabetic patients shown to have microangiopathy [ 23 , 44 , 48 ]. To the best of our knowledge, PPCs have never been described in glioblastoma; therefore, although an investigation of the role of PPCs is well beyond the scope of this work, we must not ignore the fact that these cells have been suggested to be involved in neoplastic perivascular cell differentiation, vascular survival, and cancer-related angiogenesis, aspects of primary importance in these extremely vascularized tumours [ 24 ].…”

Occurring ofIn VitroFunctional Vasculogenic Pericytes from Human Circulating Early Endothelial Precursor Cell Culture

“…So far, pericytes have been considered to be mainly vascular wall-resident cells [ 5 , 29 , 42 ]. Circulating pericytes have been only detected in a few studies [ 10 , 43 ] without subsequent isolation and expansion in vitro . Moreover a significant increase in circulating pericytes has only been detected in cancer patients, compared with healthy control, and it has been used as a prognostic oncogenic marker without any chance for further deployment in a regenerative medicine context.…”

Pro-angiogenic Role of Insulin: From Physiology to Pathology

“…The functionality of IRs on pericytes has been studied using cells isolated from bovine retinal capillaries, in which insulin induced a slow hyperpolarization in a dose-dependent manner (Fadini et al, 2012). Further characterization analyses revealed the participation of both Kir and small-conductance Ca 2+ -sensitive potassium channels in the insulin-induced hyperpolarization of these cells.…”