Saving limbs using gene therapy and stem cells
By: Felicia Breedy
In the December 9, 2009 edition of Medical News Today, Dr. Gregg Semenza, MD, PhD, has published findings that could improve a common condition of diabetes called blood vessel blockage. Blood vessel blockage can lead to low blood flow and results in low oxygen which can kill cells and tissues. “People with diabetes have a 40 times higher risk of losing a limb to amputation”, explains Dr. Semenza. With his previous Research Award, Dr. Semenza has developed a mice model that can increase blood flow, improve movement and decrease tissue death thus eliminating the need for amputation. Dr. Semenza’s research project entitled “Interaction of diabetes, aging, and HIF-1 deficiency in peripheral vascular disease” was conducted at Johns Hopkins University School of Medicine in Baltimore, Maryland.
Previously, researchers on Dr. Semenza’s team worked with a virus that turns on genes that are necessary for building new blood vessels. The blood flow was partially restored in the animals that were treated. Researcher still wanted to know if the same virus could improve blood flow in animals with diabetes. The team tested both mice with diabetes and mice without diabetes and that had reduced blood flow in one leg. Twenty-one days after treatment, the viral mice exhibited an 85% recovery of blood flow compared with 24% of the mice without diabetes.
In the current study, a new question was posed. Could the same gene therapy be used to help improve the flow of reduced blood in those with advancing age? Researchers compared 13-month old mice with 3-month old mice and found that the treatment caused all older mice to lose their legs whereas only a third of the younger mice lost their legs. The team also treated the young and old mice with the virus; however, it did not make a noticeable difference in the older mice. What was known was that one of the cells activated for new vessel growth were stem cells that grow on bone marrow. Returning to the lab, the researchers treated the mice with both the virus and injected bone marrow and found that the treated older mice were less likely to lose their legs than their counterparts.
Dr. Semenza states, “Our results are promising because they have demostrated that a combination of gene and cell therapy can improve the outcome in the case of critical limb ischemia associate with ages or diabetes. And that’s critical for bringing such treatment to the clinic.”
(Rey S, Lee K, Wang CJ, Gupta, Chen S, McMillan A, Bhise N, Levchenko A, Semenza GL. Synergistic effect of HIF-1alpha gene therapy and HIF-1-activated bone marrow-derived angiogenic cells in a mouse model of limb ischemia. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20399-404. Epub 2009 Nov 30.)
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