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Adv cel sci tissue cul 2017 | Volume 1 Issue 2
Cell Science, Stem Cell Research &
Pharmacological Regenerative Medicine
November 29-30, 2017 | Atlanta, USA
Annual Congress on
L
ung 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 immune-
suppressing 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.
Speaker 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.
e:
Woodring.Wright@UTSouthwestern.eduWoodring E Wright
UT Southwestern Medical Center, USA
The creation of artificial lungs from decellularized tissue