Restoring stem cell mobilization to promote vascular repair in diabetes.
Diabetes triggers endothelial dysfunction, which is linked to increased risk of cardiovascular diseases. Stem and progenitor cells from the bone marrow are involved in the maintenance of vascular integrity. Diabetic patients show a dysfunction of these cells, which might represent a novel pathophysiological mechanism of vascular disease. Specifically, stem and progenitor cells fail to egress from the bone marrow (BM) due to BM pathological alterations and unresponsiveness to mobilizing stimuli. In this review, we describe impaired stem cell mobilization in diabetes as a mechanism of failed vascular repair and we provide evidence that pharmacological strategies can restore mobilization. We discuss recent advances in the knowledge of aberrant organization of the diabetic BM and its implications for impaired mobilization. Finally, we describe in detail the pharmacological exploitation of the G-CSF/DPP-4(CD26)/SDF-1α axis as a novel strategy to improve mobilization and attain vascular repair in diabetes.
Venetian Institute of Molecular Medicine, Laboratory of Experimental Diabetology, 35100 Padova, Italy.
Mattia
M
Albiero
Angelo
A
Avogaro
Gian Paolo
GP
Fadini
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology; D054377:Chemokine CXCL12 / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000503:physiopathology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D013234:Stem Cells / Q000378:metabolism*
D054377:Chemokine CXCL12; D016179:Granulocyte Colony-Stimulating Factor; D018819:Dipeptidyl Peptidase 4