The Vasoreparative Function of Myeloid Angiogenic Cells Is Impaired in Diabetes Through the Induction of IL1β
| Autor: | Aoife M. Egan, Jasenka Guduric-Fuchs, Sarah Chambers, Kiran J McLoughlin, Aaron Liew, Christina L. O'Neill, Reinhold J. Medina, Timothy O'Brien, Alan W. Stitt |
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| Rok vydání: | 2017 |
| Předmět: |
critical limb ischemia
0301 basic medicine Adult Myeloid complications Adolescent Angiogenesis Interleukin-1beta nitric-oxide myeloid angiogenic cells Biology Cell therapy angiogenesis 03 medical and health sciences Paracrine signalling Young Adult Immunophenotyping Diabetes mellitus retinopathy il1 beta medicine Diabetes Mellitus acute myocardial-infarction pulmonary arterial-hypertension Macrophage Humans Myeloid Cells Interleukin 4 endothelial progenitor cells Aged therapy Cell Biology trial Middle Aged medicine.disease ami 030104 developmental biology medicine.anatomical_structure Cancer research Molecular Medicine cell therapy Developmental Biology |
| Zdroj: | Stem cells (Dayton, Ohio). 36(6) |
| ISSN: | 1549-4918 |
| Popis: | Myeloid angiogenic cells (MACs) promote revascularization through the paracrine release of angiogenic factors and have been harnessed as therapeutic cells for many ischemic diseases. However, their pro-angiogenic properties have been suggested to be diminished in diabetes. This study investigates how the diabetic milieu affects the immunophenotype and function of MACs; both MACs isolated from diabetic conditions, and healthy cells exposed to a diabetic environment to determine the potential of MACs as a cell therapy for diabetic-related ischaemia. MACs were isolated from human peripheral blood and characterized alongside pro-inflammatory macrophages M (LPS+IFNγ) and pro-angiogenic macrophages M (IL4). Functional changes in MACs in response to high-D-glucose were assessed using an in vitro 3D-tubulogenesis assay. Phenotypic changes were determined by gene and protein expression analysis. Additionally, MACs from type 1 diabetic (T1D) patients and corresponding controls were isolated and characterized. Our evidence demonstrates MACs identity as a distinct macrophage subtype that shares M2 pro-angiogenic characteristics, but can be distinguished by CD163hi expression. High-D-glucose treatment significantly reduced MACs pro-angiogenic capacity, which was associated with a significant increase in IL1β mRNA and protein expression. Inhibition of IL1β abrogated the anti-angiogenic effect induced by high-D-glucose. IL1β was also significantly up-regulated in MACs isolated from T1D patients with microvascular complications compared to T1D patients without microvascular complications or non-diabetic volunteers. This study demonstrates that Type 1 diabetes and diabetic-like conditions impair the pro-angiogenic and therefore regenerative capacity of MACs, and this response is mediated by IL-1β. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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