Emerging roles of hematopoietic cells in the pathobiology of diabetic complications

• Hyperglycemia directly compromises the function of bone marrow (BM) cells.
• Hyperglycemia produces a microenvironment (stem cell niche)-dependent defect in hematopoietic stem cell mobilization.
• Hyperglycemia-induced dysregulated hematopoietic cells travel to organs affected by diabetes.
• The dysregulated hematopoietic cells cause inflammation, cellular dysfunction, and accelerated apoptosis.

Diabetic complications encompass macrovascular events, mainly the result of accelerated atherosclerosis, and microvascular events that strike the eye (retinopathy), kidney (nephropathy), and nervous system (neuropathy). The traditional view is that hyperglycemia-induced dysregulated biochemical pathways cause injury and death of cells intrinsic to the organs affected. There is emerging evidence that diabetes compromises the function of the bone marrow (BM), producing a stem cell niche-dependent defect in hematopoietic stem cell mobilization. Furthermore, dysfunctional BM-derived hematopoietic cells contribute to diabetic complications. Thus, BM cells are not only a victim but also an accomplice in diabetes and diabetic complications. Understanding the underlying molecular mechanisms may lead to the development of new therapies to prevent and/or treat diabetic complications by specifically targeting these perpetrators.