Pig stem cells offer another approach to develop human organs for transplantation

Pig stem cells offer another approach to develop human organs for transplantation

Overview

  • Post By : Kumar Jeetendra

  • Source: University of Maryland

  • Date: 18 Dec,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 generated stem cells from cows, when injected into embryos, contributed to the growth of only the organ of interest (the embryonic intestine 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 aim of leveraging the capacity of stem cells to treat terminal diseases that would otherwise require organ transplants, either by preventing the need for transplant entirely or developing a new pipeline for developing transplantable human organs.

With the number of people who suffer from organ failures and the 20 deaths per day from the U.S. alone from a lack of available organs for transplant, finding a new way to supply organs and therapeutic alternatives to transplant patients is a crucial need. In this paper, Telugu and his staff are sharing their first steps towards developing 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. 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.”

Bhanu Telugu, Department of Animal and Avian Sciences, University of Maryland

Telugu and his group 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 safeguard the intellectual property, Telugu worked with the UMD Office of Technology Commercialization (OTC) to secure patents and start the work up for additional fundraising to carry this technology during the preclinical and clinical stages. The Maryland Stem Cell Foundation provided some funding to advance this work, and Telugu is thankful that Maryland funds technology in the human stem cell space.

“There are several terminal cases where people need some type of an organ replacement, such as organ failure and degenerative diseases that can’t be cured by drugs,” explains Telugu. “The conventional paradigm is to find a donor organ, but as of now there are still thousands of patients awaiting transplants, and there is no keeping up with the demand.

Scientists have thought for a long time that stem cells might help solve this issue, and these stem cells have the ability to go into a particular organ instead of those that enter any lineage. In this case, you can differentiate the cells and put them where they’re needed to help rescue a diseased organ, eliminating the need for transplant or at least buying the patient some time.

Only making the human liver and collecting them early from a neonatal piglet, the hepatocyte [liver] cells alone are a $3 billion opportunity annually. And later on, we can move into organ transplantation, first with the liver, and then looking at other organs of interest like the lungs and pancreas.”

According to Telugu, this has distinct benefits over other methods that researchers are now using to create donor organs in pigs, since the organs Telugu and his group are working with are actually of human origin and are consequently more likely to be accepted when transplanted. “Transplant rejections are pretty common between humans and humans,” says Telugu,”and if it’s such a problem normally, you can imagine how an organ from a pig could be difficult to accept and might not essentially perform the same functions. Pig proteins may not function the same, so that remains a massive barrier for other methods that aren’t really growing fully human organs such as ours.”

This function has the potential to address 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 constantly examine the issue and try to find solutions to them,” says Telugu. “Most animal scientists run by searching for solutions, so integrating entrepreneurship and research to get this to the market where it is needed is essential. We are among the few groups on Earth that are working in this area, and we’ve got a terrific team of embryologists here at Maryland to do this work. We’re uniquely positioned to achieve this with both genome editing and stem cell biology expertise, and being able to prove the concept with this paper is a excellent first step towards our targets.”

Source:
Journal reference:

Park, C.H., et al. (2020) Extraembryonic Endoderm (XEN) Cells Capable of Contributing to Embryonic Chimeras Established from Pig Embryos. Stem Cell Reportsdoi.org/10.1016/j.stemcr.2020.11.011.

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