Medical Minute 5-2: Designing Bodies in a Lab

By: Vanessa Welch Email
By: Vanessa Welch Email

July 11th, 2006 is the day Stephen Bruno waited 16 years for.

"You're not living. You're surviving, and you're not sure of when it's going to come, or if it's going to come," said Stephen Bruno.

'It' is a liver. And it finally came. What's happening inside a lab could put an end to the wait Stephen and thousands of others face each year. Researchers at the Institute for Regenerative Medicine at Wake Forest Baptist Medical center are the first in the world to use human liver cells to create miniature livers.

"We can actually see the little liver," said Pedro M. Baptista Pharm.D., Ph.D., Research Fellow, Wake Forest Baptist Medical Center.

Stem cells are grown on scaffolds -- creating a tiny organ.

"For the first time, we might have a solution to bypass liver transplantation, which is a major health problem throughout the world," said Shay Soker, Ph.D., Professor of regenerative Medicine at Wake Forest Baptist Medical Center.

Within a year, Harvard Doctor Joseph Vacanti will be transplanting ears grown on a scaffold onto a person. Doctor Vacanti became known throughout the world in the nineties when he grew a human ear on the back of a mouse. Now, he's using a person's own stem cells to do the very same thing.

"Ideally, it would be indistinguishable from a human ear," said Joseph P. Vacanti, Ph.D., Harvard Medical School.

But it doesn't stop there. Scientists at Cornell are developing artificial wombs in which embryos can grow outside of a woman's body. U-K scientists have built an artificial stomach that mimics both the physical and chemical reactions taking place during digestion. In Cincinnati, scientists are testing bacteria-resistant skin cells that can sweat, tan and fight off infection and ultimately generate real skin.

Zebrafish are being studied at Duke. The way they can regenerate their fins could help scientists discover how to regenerate limbs for amputees.

"They can regenerate a severed spinal cord and an amputated fin," said Ken Poss, Ph.D., Developmental Biologist at Duke University/Howard Hughes Medical Institute.

Within two weeks of amputation, zebrafish can regenerate all of their tail fin -- color pattern included. These breakthroughs come just a decade after the genome was untangled, which leads to this year's breakthrough -- the first artificial cell was born in Craig Venter's laboratory, which raises the question: Is the life line being crossed?

"It raises concerns that engineers are running amuck in biology labs and are playing God," said James Collins, Ph.D., Professor of Biomedical Engineering at Boston University.

But researchers stress they are not creating life --only modifying life by working with cells that are already living. Giving a second chance of life to millions of people who desperately need it.

For more information on other series produced by Ivanhoe Broadcast News contact John Cherry at (407) 691-1500, jcherry@ivanhoe.com.

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MEDICAL BREAKTHROUGHS - RESEARCH SUMMARY:

BACKGROUND: According to the U.S. Department of Health and Human services, an average of 75 people receive organ transplants each day. An average of 20 people die each day waiting for transplants that do not happen because of the shortage of donated organs. Every 11 minutes, someone is added to the organ donation waiting list, so the list is always changing.

GROWING MINIATURE LIVERS: Researchers at the Institute for Regenerative Medicine at Wake Forest Baptist Medical Center are the first to use human liver cells to successfully engineer miniature livers that function in a laboratory setting just like human livers. The hope is that once the organs are transplanted, they will maintain and gain function as they develop. The engineered livers are about an inch in diameter and weigh about .20 ounces. They would have to weigh about 1 pound to meet the minimum needs of the human body. To engineer the organs, scientists used animal livers that were treated with a mild detergent to remove all cells, leaving only the collagen or support structure. They then replaced the original cells with two types of human cells: immature liver cells known as progenitors and endothelial cells that line blood vessels. These cells were introduced into the liver skeleton through a large vessel that feeds a system of smaller vessels in the liver. Then, the liver was placed in a bioreactor -- special equipment that provides a constant flow of nutrients and oxygen throughout the organ. After a week, the scientists documented the progressive formation of human liver tissue as well as liver-associated function. They also observed cell growth inside the bioengineered organ.
(SOURCE: Wake Forest Baptist Medical Center)

ZEBRAFISH: Zebrafish are highly-regenerative animals that are equipped to re-grow amputated fins; injured retinae; transected optic nerves and spinal cord; and resected heart muscle. Within two weeks of amputation, zebrafish can regenerate all of their tail fin. Investigators at Duke are studying the biology of the zebrafish's regenerative events in hopes of discovering new cellular mechanisms. These fish could also help scientists come up with ways to regenerate limbs for amputees. Years ago, these researchers found that zebrafish regenerate cardiac muscle after removal of 20 percent of the ventricle with little or no scarring.
(SOURCE: Duke University)

FOR MORE INFORMATION, PLEASE CONTACT:
Karen Richardson, Sr. Communications Manager
Wake Forest Institute for Regenerative Medicine
Winston-Salem, NC
krchrdsn@wfubmc.edu

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Shay Soker, PhD, Professor of Regenerative Medicine at Wake Forest Baptist Medical Center talks about designing livers in the lab.

What is the goal of this research with the liver? What are you trying to develop?

Dr. Soker: What we are trying to develop is a whole organ. In contrast to what tech engineers are currently doing with small tissue and pieces of tissue. What we are trying to create here is a whole organ that would be functional and that would have a complete and functional vascular network to feed all the cells within the organ.

In a very general sense, how do you do it? You need a scaffold, and then you put cells in the scaffolds. Can you explain that for me?

Dr. Soker: Exactly, the scaffold is the structure that holds the functional cells. Because the liver is very complex, we decided to acquire these structures from animals. So, we take animal livers and we remove all the animal cells and then we put in human cells instead and now we have a human liver on an animal liver structure.

What are the potential uses for livers like this?

Dr. Soker: Obviously, the main purpose would be to produce livers for transplant for patients who have acute or aphonic liver disease -- their liver doesn’t function, and they are at risk of death, and they don’t have an organ donated for them. There are two other purposes for our research: one is to produce a system that would allow us better development of an organ such as the liver and the third purpose would be to provide liver tissue that could be used by toxicologists for testing.

There are still some hurdles though; this is not a slam-dunk just yet?

Dr. Soker: No, the main hurdle is the number of the cells and the size of the organ. Right now, we are able to make a liver of the size that can rescue a rat. But we will have to expand the size to about 100-fold in order to get to a human size liver.

And so, the liver you have now would be way too small to support a person?

Dr. Soker: That is correct. However, we are not aiming at providing a fully-loaded human liver. A human can live with about 10% of its liver and survive until there is a donated liver or until there are more livers that we could produce that would sustain a patient for a longer period of time.

How exciting is it to work on a project like this?

Dr. Soker: It’s very exciting because, I think, that for the first time, we might have a solution to bypass liver transplantation, which is a major health problem throughout the world.


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