DiMuzio, Paul Joseph
A stem cell vascular graft
General Research Subject: Both Type 1 And Type 2 Diabetes
Focus: Complications\ Macrovascular-Atherosclerotic CVD and Human Diabetes, Stem Cell Research\Human\Adult
Type of Grant: Innovation
Project Start Date: July 1, 2011
Project End Date: June 30, 2013
The care of diabetic patients often requires surgery to treat occluded heart arteries and establish access for hemodialysis. Unfortunately, outcomes are complicated by the use of inferior vascular grafts. The main purpose of this project is to evaluate an alternative vascular graft composed of the patient's own adult stem cells derived from adipose tissue (ASC). The authors have pioneered the creation of this graft and have demonstrated that the stem cells, unlike those taken from blood or bone marrow, are abundant in diabetics. In the proposed studies, the authors will first compare the differentiation of ASC taken from diabetic vs. non-diabetic patients into cells that naturally line blood vessels (endothelial cells, EC). Tissue-engineered stem cell grafts, composed of autologous EC-differentiated ASC, will then be tested in an animal model to examine their function over six months. Second, differentiation will be evaluated in the context of manufacturing a graft for clinical usage; specifically, this will involve removal of all foreign proteins from the graft creation process as well as testing the effects of freezing the grafts (a process necessary to make the grafts readily available and transportable). The results from ASC taken diabetic vs. non-diabetic patients will be compared and the resultant graft tested in animals. Ultimately, this study will: 1) further our understanding of the use of adult stem cells from diabetics in tissue engineering, and 2) provide pre-clinical data necessary to perform a pilot trial of the stem cell graft in humans.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
Diabetes often results in blocked arteries, especially those that supply the heart and extremities with blood. These blockages may result in heart attack and limb loss-two unfortunate and common outcomes in late stage diabetes. Diabetes also affects the kidneys, and is a major cause for renal failure necessitating institution of hemodialysis. In each of these situations, treatment often involves the creation of a bypass around the blocked arteries or creation of vascular access for hemodialysis. The gold standard graft for these procedures is the patient's own natural vascular tissue; unfortunately, this tissue may not be available for use and the patient undergoes surgery using plastic grafts. These prosthetic grafts are notorious for clotting off or getting infected, often with disastrous results.
This project evaluates an alternative vascular graft to be used in the difficult situations where the diabetic patient requires surgery but does not have enough of his/her own tissue for success. The graft is composed of a natural vascular scaffold (human vein that is decellularized to reduce rejection) seeded with the patient's own adult stem cells derived from fat. During the graft creation process, the cells are differentiated into endothelial cells, those that naturally line our blood vessels. This project specifically addresses the practicality and efficacy of creating these grafts in diabetic patients.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
This project is designed to improve the treatment of diabetic complications that are commonly treated by cardio-vascular surgical procedures including heart and leg artery bypass and the creation of vascular access for the institution of hemodialysis. Many diabetics require these types of surgeries, the outcomes of which are dependent upon the patient having enough of their own vascular tissues to use for success. Quite often this tissue is unavailable and use of alternative grafts, mainly composed of plastic, have far inferior results. This project is designed to understand the practicality of creating an alternative bypass graft composed of the diabetic patient's own adult stem cells from fat. In sum, success of this project may lead to a new treatment for those diabetics suffering from coronary artery disease, peripheral vascular disease and kidney failure.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
As a practicing vascular surgeon for over 15 years, I have attended to many diabetic patients who have required bypass of heart and leg arteries as well as those who require access for hemodialysis. I have also treated many patients who have undergone surgery with prosthetic grafts and have experienced inferior outcomes in terms of poor graft function and infection. These can be devastating problems that can lead to death, limb loss and other severe morbidities.
It is important for me to be involved in this research so we can
improve the treatments of these difficult and severe diabetic
complications. Having a better bypass graft will save lives, improve
outcomes and save our health system significant amounts of money. This
award directly impacts my research to create a better bypass graft for
use 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 the body. Intense research is
necessary from all angles including understanding its causes, effecting
preventative measures and cures, and improving the treatments of
diabetic complications. This is an enormous task. I believe it is
critical that future diabetic research is directed towards work that
directly translates into improvements in the prevention, cure and care
of these unfortunate patients. As a vascular surgeon, up to half of my
patients are diabetics requiring surgery to treat complications of their
disease. Unfortunately, our treatments themselves can be fraught with
complications. Research designed to improve the care of these patients
will be a great benefit to the individual as well as to society.
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