Bringing the Dysfunctional Bone Marrow of Diabetics Back to Life

One of the most insidious consequences of diabetes mellitus is its nocuous effects on the ability of the circulatory system to repair itself. The small vessels within our organ undergoes constant remodeling and repair in response to the wears and tears of life. Diabetes seriously decreases the ability of the circulatory system to execute this repair.

This day-to-day circulatory repair relies upon a group of bone marrow stem cells known as “bone marrow-derived early outgrowth cells or EOCs, and EOCs from patients with diabetes mellitus are impaired in their ability to repair the circulatory system (See Fadini GP, Miorin M, Facco M et al. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol 2005;45:1449–1457).

Is there are way to reverse this destructive trend? There is a protein known as SIR1, which stands for Silent Information Regulator 1. This gene product regulates aging and the formation of blood vessels, and might very well play a role in the diabetes-induced decrease in blood vessels repair and EOC impairment.

To answer this question, the laboratory of Richard E. Gilbert from the University of Toronto, Toronto, Ontario, Canada, used drugs to increase SIR1 activity in EOCs from diabetic rodents to determine if such treatments abrogated the diabetes-induced decrease in EOC function.

Gilbert’s lab isolated EOCs from normal and diabetic mice and subjected them to a variety of tests. They determined how many blood vessel-inducing molecules were made by these cells, and the EOCs from diabetic mice produced much less of such molecules and had reduced levels of SIR1.  EOCs from diabetic mice also performed poorly in blood vessel-making assays in culture dishes.

Would kicking up the levels of SIR1 in EOCs from diabetic mice improve the function of their EOCs? By using a drug to increase SIR1 activity in EOCs, GIlbert and others were able to show that increased SIR1 activity in EOCs from diabetic mice restored their production of blood-vessel-inducing molecules, and also improved their ability to make blood vessels in culture.

This extraordinary publication shows that the diminished abilities of bone marrow from diabetic or aged individuals is not irreversible. Perhaps research such as this can spur the discovery of drugs that reserve the decline of SIR1 activity in diabetics and aged patients to beef up their circulatory self-repair mechanisms.

See Darren A. Yuen, et al., “Angiogenic Dysfunction in Bone Marrow-Derived Early Outgrowth Cells from Diabetic Animals Is Attenuated by SIRT1 Activation,” Stem Cells Translational Medicine 2012;1:921–926.