Effects of Treatment for Diabetes Mellitus on Circulating Vascular Progenitor Cells

Kusuyama, Takanori; Omura, Takashi; Nishiya, Daisuke; Enomoto, Soichiro; Matsumoto, Ryo; Takeuchi, Kazuhide; Yoshikawa, Junichi; Yoshiyama, Minoru

doi:10.1254/jphs.fp0060256

Cited by 60 publications

(48 citation statements)

References 15 publications

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“…23,24 Preclinical and clinical studies have convincingly described the detrimental effects of diabetes on EPC number and function, 4,25,26 and our data confirm the findings of previous reports that diabetes impairs EPC function. This effect of diabetes on EPC may be mediated by an increased consumption of EPCs due to their anchoring to diffusely damaged arteries or to a more central impact on bone marrow.…”

Section: Discussionsupporting

confidence: 91%

“…In a previous study, EPC number was found to be significantly related to HbA1c and blood sugar levels in diabetes, and improved glycemic control was found to significantly increase EPC numbers. 26 In particular, in the present study, HbA1c level was found to be an independent predictor of a low CFU number, which suggests that degree of glycemic dysregulation directly affects EPC function.…”

Section: Discussionsupporting

confidence: 54%

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Circulating Endothelial Progenitor Cells as a New Marker of Endothelial Dysfunction or Repair in Acute Stroke

Chu

Jung²,

Park

et al. 2008

Stroke

107

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Background and Purpose-Understanding on distinct subsets of endothelial progenitor cells may provide insights of endothelial dysfunction or repair in the acute ischemic event. Recent in vitro data have reported the colony-forming unit (CFU) and outgrowth cell population as a subset of endothelial progenitor cells. In this study, we undertook to validate the significance of CFU number and outgrowth cell yield in acute stroke. Methods-Mononuclear cells were isolated from the peripheral blood of 75 patients with acute stroke, 45 patients with chronic stroke, and 40 age-matched healthy volunteers. CFU numbers were counted after culturing them for 7 days, and outgrowth cell appearance was measured during the 2 months of culture. Endothelial progenitor cell function was also evaluated by matrigel plate assays. Independent parameters predicting CFU number and outgrowth cell yield were assessed using logistic regression analysis. Results-The CFU numbers and tube formation abilities in matrigel assays were significantly reduced in patients with acute stroke compared with patients with chronic stroke or healthy control subjects. Moreover, patients with large artery atherosclerosis had much lower CFU numbers and functional activities than ones with cardioembolism. Outgrowth cells were isolated from 10% of healthy control subjects and 22% of patients with chronic stroke during the cultures, but from 71% of patients with stroke. Multivariate analysis identified glycosylated hemoglobin and National Institutes of Health Stroke Scale on admission as significant independent predictors of a low CFU number and a high isolation frequency of outgrowth cells, respectively. Conclusion-CFU number may thus represent an accumulated endothelial progenitor cell dysfunctional status, whereas outgrowth cell appearance may reflect the resilience of the systemic circulation to acute ischemic stress.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 54%

Circulating Endothelial Progenitor Cells as a New Marker of Endothelial Dysfunction or Repair in Acute Stroke

Chu

Jung²,

Park

et al. 2008

Stroke

107

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“…In contrast to diabetic neuropathy, which is characterised by microvascular dysfunction, patients with diabetic retinopathy present significant capillary proliferation in the retina [36]. We report here a significant reduction in putative EPCs in patients with diabetic retinopathy, a finding which agrees with some, but not all, published studies [37,39,40]. How angiogenesis can be increased in the presence of reduced EPC levels in these patients is not clear and actually represents a paradox [39].…”

Section: Discussionsupporting

confidence: 80%

“…c Subgroup analysis of the MVD group identified both neuropathy (Neu; n=17) and retinopathy (Ret; n=29) as complications whereby progenitor cell levels were further decreased in type 2 diabetic patients. [18][19][20]37]. We also noted a generalised reduction in putative EPCs in patients with MVD.…”

Section: Discussionsupporting

confidence: 60%

Generalised reduction of putative endothelial progenitors and CXCR4-positive peripheral blood cells in type 2 diabetes

et al. 2008

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Aims/hypothesis In patients with type 2 diabetes, reduced levels of circulating endothelial progenitor cells have been reported and these have been correlated with disease severity. In this study, we examined a panel of markers widely used to identify progenitor and/or stem cells, and determined their association with disease severity in diabetic patients. Since expression of chemokine (C-X-C motif) receptor 4 (CXCR4) has been associated with mobilisation and recruitment of progenitor cells, CXCR4 expression was also analysed. Methods Peripheral blood mononuclear cells (PBMCs) from 98 patients with type 2 diabetes and 39 control individuals were analysed by flow cytometry for surface marker expression. Results Cells expressing different combinations of progenitor and/or stem cell markers were severely reduced in PBMCs of diabetic patients compared with those of control participants. Moreover, a number of these putative progenitor cell populations were negatively associated with disease severity. Reduced expression of CXCR4 and CD34/CXCR4-positive cells was also observed in diabetic patients. PBMCs expressing CXCR4 positively correlated with levels of progenitor cells in control participants but not in diabetic patients. Levels of putative progenitor and CXCR4-positive cells were further decreased in patients with diabetic complications, including cardiovascular and microvascular diseases. Conclusions/interpretation A generalised decrease in a range of progenitor cell populations was observed in type 2 diabetic patients. This reduction was also negatively associated with disease severity.

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“…5,6 Recent evidences support the notion that type 1 and type 2 diabetic patients have diverse number of circulating EPCs. 7,8 Increasing evidence suggests that circulating EPCs contribute to pathological neo-vascularization in diabetes induced retinal stress. 9 EPCs have the potential to home to the sites of tissue ischemia and contribute to vascular repair.…”

Section: Introductionmentioning

confidence: 99%

Differential Modulation of Circulating Endothelial Progenitor Cells in Peripheral Blood Monocyte Population of an Early Stage of Streptozotocin-Induced Diabetic Retinopathy

Muthaian¹,

Raveendran²

2016

JYP

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Male Wistar rats weighing 220-250 g were used for this study. The animals were individually acclimatized and fed a standard commercial diet and water ad libitum for 7 days. The 12 h light and 12 h dark cycle was followed throughout the study period. All the experiments and Retinal microvascular complications in STZ induced diabetic Wistar rats were validated after 4 months using trypsin digestion assay of retinal vasculature, histological analysis of retina, glial fibrillary acidic protein (GFAP) immunostaining. Subsequently, circulating EPCs were quantified in PBMCs from diabetes induced rats after 4 months using markers such as CD-34, CD-31, CD-146, VE-Cadherin and Flk-1 by flow cytometry. Results: Pericyte loss, acellular capillaries, retinal layer thickness, microglial activation and increased nitric oxide (NO) levels were observed after 4 months of diabetes induction. Whereas the EPC markers. While the EPC markers such as CD-34, CD-31, VE-Cadherin were decreased, the Flk-1+ve cells were up-regulated in the endogenous EPC pool. Conclusion: The quantity of EPCs is modulated in diabetes which may provide an insight into the use of EPCs as a biomarker for the progression of diabetes induced microvascular complication.

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Effects of Treatment for Diabetes Mellitus on Circulating Vascular Progenitor Cells

Cited by 60 publications

References 15 publications

Circulating Endothelial Progenitor Cells as a New Marker of Endothelial Dysfunction or Repair in Acute Stroke

Circulating Endothelial Progenitor Cells as a New Marker of Endothelial Dysfunction or Repair in Acute Stroke

Generalised reduction of putative endothelial progenitors and CXCR4-positive peripheral blood cells in type 2 diabetes

Differential Modulation of Circulating Endothelial Progenitor Cells in Peripheral Blood Monocyte Population of an Early Stage of Streptozotocin-Induced Diabetic Retinopathy

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