Bone marrow dysfunction in diabetes

Autor: Fadini, Gian Paolo
Rok vydání: 2013
Předmět:
Popis: Background. Diabetes mellitus (DM) increases cardiovascular disease (CVD) and this is attributed, at least in part, to shortage of vascular regenerative cells derived from the bone marrow (BM). Indeed, the BM harbours several subsets of progenitor cells for endothelial, smooth muscle cells and cardiomyocytes, which derive from a common CD34+ ancestor. Recent data from experimental models of type 1 and type 2 diabetes highlight BM pathologies that include microangiopathy, neuropathy, altered gene expression and niche dysfunction. Aims. The set of experiments herein described aim to portray the alterations of BM function in clinical and experimental diabetes. Methods. The approaches are diversified and include: 1) A prospective trial of direct BM stimulation with human recombinant granulocyte colony stimulating factor (G-CSF) in diabetic and non diabetic patients; 2) A meta-regression analysis of trials using G-CSF to stimulate cardiovascular repair in diabetic and non diabetic patients; 3) A study of stem/progenitor cell compartmentalization in the BM and peripheral blood (PB), in relation to diabetes; 4) An animal study to dissect the role of DPP-4 dysregulation in the impaired stem/progenitor cell mobilization induced by diabetes. Results. Part 1: in response to G-CSF, levels of CD34+ cells and other progenitor cell phenotypes increased in non DM subjects. DM patients had significantly impaired mobilization of CD34+, CD133+, CD34+CD133+ hematopoietic stem cells and CD133+KDR+ endothelial progenitors, independently of potential confounders. The in vivo angiogenic capacity of circulating mononuclear cells increased after hrG-CSF in non DM controls, but not in DM patients. DM was associated with inability to upregulate CD26/DPP-4 on CD34+ cells, which is required for the mobilizing effect of G-CSF. Part 2: for the meta-regression analysis 227 articles were screened, 96 were retrieved for evaluation and 24 retained for the analysis of the primary end-point. There was a strong negative correlation between prevalence of diabetes and achieved CD34+ cell levels after G-CSF stimulation (r=-0.68; p
Databáze: OpenAIRE
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