News & Research

    University of Louisville, Louisville, Kentucky

Promotion of diabetic ischemic angiogenesis by SDF-1betaP2G mobilizing and SDF-1beta recruiting endothelial progenitor cells

General Research Subject: Type 2 Diabetes

Focus: Complications, Complications\Macrovascular-Cellular Mechanisms of Atherogenesis in Diabetes, Foot Care\Lower Extremities, Integrated Physiology\Muscle

Type of Grant: Junior Faculty

Project Start Date: January 1, 2013

Project End Date: December 31, 2015

Diabetes Type: Type 2 diabetes

Research Description

Diabetic vascular complications are mainly due to lack of new blood vessel formation so that formation of stable blood vessels is an important step for the restoration of blood flow and injured organ function. Current clinical treatment and management of diabetic complications are heavily based on pharmacological treatment that, in most cases, barely affects the blood vessel regeneration. Thus there is an urgent need for therapeutic interventions that can accelerate the repair of impaired blood vessels and restoration of blood flow, to stimulate tissue regeneration. A promising, new therapeutic option for the repair of diabetic damage to blood vessel and end-organs is the use of endothelial progenitor cells (EPCs). However, diabetes reduces EPCs in the blood and also abrogates chemokines responsible for EPCs migration to ischemic tissues.

Recently, the PI developed a new peptide, named SDF-1betaP2G (P2G). The PI¡¯s preliminary studies demonstrated that P2G can effectively improve new blood vessel formation and blood flow restoration in both diabetic and non-diabetic mouse models. P2G also significantly increased EPCs in the blood. Based on these new findings, the PI proposed to combine use of P2G to mobilize EPCs into circulation with the administration of SDF-1beta (a chemokine) to attract EPCs into ischemic tissue to treat hind-limb ischemic damages in high fat diet-induced and transgenic spontaneous type 2 diabetic animal models.

The successful implementation of this study will provide substantial data regarding the potential clinical application of P2G for therapy of diabetic peripheral vascular diseases in diabetic patients.

Research Profile

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating, and curing diabetes?

Our project covers developing a novel therapeutic strategy for treatment of diabetic peripheral vascular complication using a Our project covers developing a novel therapeutic strategy for treatment of diabetic peripheral vascular complication using a high fat diet induced type 2 diabetic model. Diabetic vascular complications are mainly due to lack of new blood vessel formation so that formation of stable blood vessels is an important step for the restoration of blood flow and injured organ function. Current clinical treatment and management of diabetic complications are heavily based on pharmacological treatment that, in most cases, barely affects the blood vessel regeneration. Thus there is an urgent need for therapeutic interventions that can accelerate the repair of impaired blood vessels and restoration of blood flow, to stimulate tissue regeneration. A promising, new therapeutic option for the repair of diabetic damage to blood vessel and end-organs is the use of endothelial progenitor cells (EPCs). However, diabetes reduces EPCs in the blood and also abrogates chemokines responsible for EPCs migration to ischemic tissues.

Recently, we developed a new peptide, named P2G. We have found that P2G can effectively improve new blood vessel formation, blood flow restoration and increase EPCs mobilization in our preliminary study. This project will particularly support us to systemically define whether P2G can induce EPC mobilization and improve ischemic new blood vessel formation under diabetic conditions. Furthermore, this project will provide the first evidence to examine whether there is a potential for the clinical application to use the novel antagonistic peptide P2G for mobilizing EPCs into circulation and use chemokine SDF-1¦Â locally in the wound site for recruiting EPCs, resulting in an efficient therapy for diabetic peripheral vascular diseases.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

Our previous work has generated a novel therapeutic peptide with strong potency of EPC mobilization, which could be developed into a novel therapy for diabetic vascular complications and wound healing by combination with a chemokine attracting EPC migration. This project is designed to improve the treatment of diabetic complications that are commonly treated by vascular surgical procedures or amputation, which may lead to a new treatment for those diabetics suffering from peripheral vascular disease, and even coronary artery disease.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your efforts?

I have several friends and relatives are diabetic including my mother-in-law, some of them suffer from serious vascular complications. When they asked what kind of research I was doing? My answer on diabetes makes them so excited and full of expectation. But I felt great shamed and frustrated for my research cannot immediately alleviate their suffering. These things enable me decide to dedicate in diabetes research, especially translational research for all the diabetic patients like my friends and relatives over the world.

Utilization autologous EPCs in patients by mobilization and chemokine therapy will have more advantages than allogeneic EPCs transplantation and other therapies, which may dramatically improve outcomes and save our healthcare system significant amounts of money. This award will directly support me to develop a novel therapeutic strategy to be used in diabetic patients and therefore has considerable translational and transformative value.

In what direction do you see the future of diabetes research going?

Diabetes affects nearly every organ in human body. Diabetic complications result in high fatality and morbidity, and have become the leading cause of death in patients with diabetes. Therefore, to clarify the pathogenesis of diabetic complications and explore the prevention and control measures is an enormous task. I believe it is critical for our community that diabetic research is directed towards work that can be directly translates into improvements in the prevention, cure and care of diabetic patients with severe complications, but not only diabetes itself.