title: Concise review: diabetes, the bone marrow niche, and impaired vascular regeneration.
abstract: Diabetes mellitus is a global health problem that results in multiorgan complications leading to high morbidity and mortality. Until recently, the effects of diabetes and hyperglycemia on the bone marrow microenvironment-a site where multiple organ systems converge and communicate-have been underappreciated. However, several new studies in mice, rats, and humans reveal that diabetes leads to multiple bone marrow microenvironmental defects, such as small vessel disease (microangiopathy), nerve terminal pauperization (neuropathy), and impaired stem cell mobilization (mobilopathy). The discovery that diabetes involves bone marrow-derived progenitors implicated in maintaining cardiovascular homeostasis has been proposed as a bridging mechanism between micro- and macroangiopathy in distant organs. Herein, we review the physiological and molecular bone marrow abnormalities associated with diabetes and discuss how bone marrow dysfunction represents a potential root for the development of the multiorgan failure characteristic of advanced diabetes. The notion of diabetes as a bone marrow and stem cell disease opens new avenues for therapeutic interventions ultimately aimed at improving the outcome of diabetic patients.
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy; Pennsylvania Hospital, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA; Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA; Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy; Division of Regenerative Medicine, Department of Basic Clinical Science, Tokai University, Tokyo, Japan; Regenerative Medicine Section, Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom gianpaolo.fadini@unipd.it.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Fadini
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy; Pennsylvania Hospital, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA; Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA; Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy; Division of Regenerative Medicine, Department of Basic Clinical Science, Tokai University, Tokyo, Japan; Regenerative Medicine Section, Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferraro
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy; Pennsylvania Hospital, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA; Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA; Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy; Division of Regenerative Medicine, Department of Basic Clinical Science, Tokai University, Tokyo, Japan; Regenerative Medicine Section, Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
authors.forename: Federico
authors.initials: F
authors.lastname: Quaini
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy; Pennsylvania Hospital, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA; Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA; Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy; Division of Regenerative Medicine, Department of Basic Clinical Science, Tokai University, Tokyo, Japan; Regenerative Medicine Section, Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asahara
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy; Pennsylvania Hospital, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA; Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA; Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy; Division of Regenerative Medicine, Department of Basic Clinical Science, Tokai University, Tokyo, Japan; Regenerative Medicine Section, Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
authors.forename: Paolo
authors.initials: P
authors.lastname: Madeddu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D003925:Diabetic Angiopathies / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018919:Neovascularization, Physiologic; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology; D055153:Stem Cell Niche; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D001786:Blood Glucose
keywords: Complications; Regeneration; Stem cells