+44-1518-081136The creation of artificial lungs from decellularized tissue
Annual Congress on Cell Science, Stem Cell Research & Pharmacological Regenerative Medicine
November 29-30, 2017 | Atlanta, USA
Woodring E Wright
UT Southwestern Medical Center, USA
Keynote : Adv cel sci tissue cul
Abstract:
Lung failure is a major health problem, both in genetic disorders such as cystic fibrosis and following environmental insults in diseases such as emphysema and idiopathic pulmonary fibrosis. The restricted availability of histocompatible human lungs for transplantation is often a rate limiting factor for treatment. Transplanting both lungs increases patient long-term survival, but the shortage of lungs makes this controversial since it halves the number of recipients. This problem would be solved by being able to create two lungs for each patient. Lung transplantation is further complicated by chronic transplant rejection; after receiving a transplant a patient must be on immunesuppressing drugs for the rest of their lives even after tissue matching. This long term immunosuppression has significant side effects and allows only <20% of recipients to survive more than 10 years after transplantation. We will avoid both immunological and availability problems by using a patient’s own bronchial epithelial and endothelial cells to create two lungs. Previous approaches to populating decellularized lungs with bronchial epithelial and endothelial cells have met with only limited success. The introduced cells differentiated rapidly, producing only small foci of normal appearing alveolar or conducting airway histology, widely separated from other foci containing capillaries. We are overcoming these limitations by a variety of interventions to temporarily block differentiation and stimulate both proliferation and migration. Some of these approaches use chemical reagents, while others exploit oncogenes. Many oncogenes are known to block differentiation and stimulate both migration and proliferation. In preliminary experiments, we are introducing them and simply analyzing their effects on colonization of the decellularized lungs. In later experiments, these oncogenes will be under the control of inducible promoters or in cre-lox excisable constructs. All constructs will contain herpes-virus TK suicide cassettes, so that any cells that escaped excision by cre could still be eliminated by treatment with ganciclovir if they began to proliferate excessively. Ultimately, we hope to be able to create transplantable lungs on demand without any need for ongoing immunosuppression.
Biography:
Woodring E Wright received his BA degree, Summa Cum Laude, from Harvard University in 1970, a PhD under the direction of Dr. Leonard Hayflick in 1974 and an MD from Stanford University School of Medicine in 1975. Following a Post-doctoral fellowship at the Pasteur Institute in Paris, France with Dr. Francois Gros, he joined the faculty at Southwestern Medical School in Dallas, Texas in 1978, where he is now Professor of Cell Biology and Southland Financial Corporation Distinguished Chair in Geriatric Research. He has been the recipient of the Lyndon Baines Johnson Research Award of the American Heart Association, a Research Career Development award from the NIH, a Merit Award from the National Institute on Aging, an AlliedSignal Award for Research on Aging, the Hayflick Award from American Aging Association and an Ellison Medical Foundation Senior Scholar Award. He is on the Scientific Advisory Board of the Buck Institute on Aging. He is the author of more than 200 scientific publications and holds 15 US patents, with an additional eight pending.
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