Diabetes mellitus induces bone marrow microangiopathy

Area of Science:

• Hematology
• Endocrinology
• Vascular Biology

Background:

• Diabetes mellitus impacts various organ systems, but its effects on the bone marrow microenvironment are not fully understood.
• The bone marrow microenvironment is crucial for hematopoietic stem cell function and maintenance.

Purpose of the Study:

• To investigate the impact of diabetes on bone marrow microvascular remodeling.
• To determine the consequences of these changes on bone marrow homeostasis and hematopoietic cell populations.

Main Methods:

• Type 1 diabetes was induced in mice.
• Bone marrow microvasculature was assessed using fluorescent microspheres and immunohistochemistry.
• Endothelial cell function, oxidative stress, senescence, and apoptosis were analyzed.
• Hematopoietic stem and progenitor cells (HSPCs) were quantified using flow cytometry.
• The therapeutic potential of benfotiamine was evaluated.

Main Results:

• Diabetic mice exhibited significant bone marrow microvascular rarefaction, reduced blood flow, and hematopoietic cell depletion.
• Diabetic bone marrow endothelial cells showed increased oxidative stress, senescence, and impaired function.
• HSPCs were predominantly depleted in hypoperfused regions of the bone marrow.
• Benfotiamine supplementation ameliorated microangiopathy, hypoperfusion, and HSPC loss.

Conclusions:

• Diabetes induces a detrimental microangiopathy in the bone marrow, compromising its integrity and function.
• Targeting oxidative stress pathways, such as with benfotiamine, may offer a therapeutic strategy for diabetic bone marrow dysfunction.