UMD Researchers Perform Crucial Proof-of-Concept Experiment, Paving the Way for Growing Human Organs for Therapeutics and Transplantation
By Samantha Watters
University of Maryland – December 17,
2020 -- In a new paper published in Stem Cell Reports,
Bhanu Telugu and co-inventor Chi-Hun Park of the University of Maryland (UMD)
Department of Animal and Avian Sciences show for the first time that newly
established stem cells from pigs, when injected into embryos, contributed to
the development of only the organ of interest (the embryonic gut and liver),
laying the groundwork for stem cell therapeutics and organ transplantation.
Telugu’s start-up company, Renovate
Biosciences Inc. (RBI), was founded with the goal of leveraging the
potential of stem cells to treat terminal diseases that would otherwise require
organ transplants, either by avoiding the need for transplants altogether or
creating a new pipeline for growing transplantable human organs. With the
number of people who suffer from organ failures and the 20 deaths per day in
the U.S. alone purely from a lack of available organs for transplant, finding a
new way to provide organs and therapeutic options to transplant patients is a
critical need. In this paper, Telugu and his team are sharing their first steps
towards growing fully transplantable human organs in a pig host.
“This paper is really about using the
stem cells from pigs for the first time and showing that they actually can be
injected into embryos and only go to the endodermal target organs like the
liver, which is very important for delivering safe therapeutic solutions going
forward,” says Telugu. “This is an important milestone. It’s a pipe dream in a
way because a lot of things need to work out between here and full organ
transplantation, but this paper sets the stage for all our future research. We
can’t really just go and start working with humans in work like this, so we
started with pig-to-pig transfer in this paper, working with the stem cells and
putting them back into other pigs to track the process to make sure it is safe
for liver production as proof-of-concept.”
Winning
the Inventor Pitch Award at UMD Bioscience Day
Telugu and his team pitched this work at
UMD Bioscience Day on behalf of his company, RBI, and received the Inventor Pitch Award and
the UMD
Invention of the Year Award in 2018. In order to protect the
intellectual property, Telugu worked with the UMD Office of Technology
Commercialization (OTC) to secure patents and open the work up for additional
fundraising to carry this technology through the preclinical and clinical
stages. The Maryland Stem Cell Foundation provided some funding to advance this
work, and Telugu is thankful that Maryland funds technologies in the human stem
cell space.
“There are many terminal cases where
people need some sort of an organ replacement, like organ failure and
degenerative diseases that cannot be cured by drugs,” explains Telugu. “The
traditional paradigm is to find a donor organ, but as of today there are still
thousands of patients waiting for transplants, and there is no keeping up with
the demand. Researchers have thought for a long time that stem cells could help
solve this problem, and these stem cells have the ability to go into a specific
organ as opposed to those that go into any lineage. In this case, you can
differentiate the cells and place them where they are needed to help rescue a
diseased organ, eliminating the need for transplant or at least buying the
patient some time. Just making the human liver and collecting them early from a
neonatal piglet, the hepatocyte [liver] cells alone are a $3 billion
opportunity per year. And in the future, we can move into organ
transplantation, first with the liver, and then looking at other organs of
interest like the pancreas and lungs.”
According to Telugu, this has distinct
advantages over other methods that researchers are currently using to create
donor organs in pigs, since the organs Telugu and his team are working with are
actually of human origin and are therefore more likely to be accepted when
transplanted. “Transplant rejections are pretty common even between humans and
humans,” says Telugu, “and if it is such a problem normally, you can imagine
how an organ from a pig could be difficult to accept and may not essentially
perform the same functions. Pig proteins may not function the same, so that
remains a huge barrier for other methods that are not actually growing fully
human organs like ours.”
This work has the potential to solve a
major problem in the treatment of organ failure and other degenerative
diseases, which is what Telugu and his work is all about. “Being a veterinarian
by training, we always look at the problem and try to find solutions to them,”
says Telugu. “Most animal scientists operate by looking for solutions, so
integrating research and entrepreneurship to get this to the market where it is
needed is essential. We are one of the few groups on the planet that are
working in this space, and we have a great team of embryologists here at
Maryland to do this work. We are uniquely positioned to accomplish this with both
genome editing and stem cell biology expertise, and being able to prove the
concept with this paper is a great first step towards our goals.”
The paper, entitled “Extra-embryonic
endoderm (XEN) cells capable of contributing to embryonic chimeras established
from pig embryos,” is published in Stem Cells Reports, DOI: 10.1016/j.stemcr.2020.11.011.
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