Concise review: diabetes, the bone marrow niche, and impaired vascular regeneration.

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.