Embryonic stem cells might help reduce transplantation rejection

September 15, 2008

Researchers have shown that immune-defense cells influenced by embryonic stem cell-derived cells can help prevent the rejection of hearts transplanted into mice, all without the use of immunosuppressive drugs.

The University of Iowa and the Iowa City Veterans Affairs (VA) Medical Center finding has implications for possible improvements in organ and bone marrow transplantation for humans. The study results appeared Friday in the online journal PLoS ONE, published by the Public Library of Science, at dx.plos.org/10.1371/journal.pone.0003212>.

People who need bone marrow or solid organ transplantation must take immunosuppressive drugs that can cause side effects nearly as severe as the disease they have. They also can experience graft-versus-host disease, which can cause death.

These problems are spurring researchers to develop methods to reduce transplantation rejection, said the study's principal investigator Nicholas Zavazava, M.D., Ph.D., professor of internal medicine and director of transplant research at the UI Roy J. and Lucille A. Carver College of Medicine.

"The idea behind the study is to 'prep' a recipient's immune system to make it receptive to the eventual organ or bone marrow donor's genetic make-up," said Zavazava, who also is a researcher and staff physician with the Iowa City VA Medical Center. "The approach involves taking embryonic stem cells with the same genetic background as the donor from which the organ or bone marrow ultimately will come and adapting them into another type of stem cell that can be injected into the recipient."

Specifically, the team treated mouse embryonic stem cells with a "cocktail" of growth factors, causing them to become blood stem cells. These cells express very low levels of so-called "transplantation antigens" and are therefore protected from immunological rejection.

The researchers then injected the blood stem cells into the recipient mouse's blood circulation. These stem cells found their way into the recipient mouse's thymus, where, as happens in humans, the recipient's own bone marrow cells typically migrate and develop into immune-defense cells known as T-cells.

With the donor-related blood stem cells now present in the thymus, the mouse recipient's own T-cells learned to recognize them as part of itself and therefore caused no rejection. These now 'donor-friendly' T-cells then circulated within the recipient mouse's blood, Zavazava explained.

"When we then transplanted into the recipient mouse a donor mouse heart that had the same genetic make-up as the previously injected stem cells, the T-cells didn't reject the heart because they recognized it as compatible," Zavazava said.

"If we could eventually use this approach for organ transplantation in humans, it would be a huge advantage over the method we're currently using," he added.

In addition to its potential for organ transplantation treatment, the embryonic stem cell-based method might also have implications for treating bone marrow diseases such as leukemia.

Because a mouse is so small, it was not possible in the study to remove the animal's existing heart and replace it with another. Thus, to test for transplant success, the study approach involved leaving the original heart intact, transplanting a second functional heart into the abdomen and then linking the transplanted heart to the aorta.

Source: University of Iowa

Explore further: Cancer drug ibrutinib found helpful in treating graft versus host disease after transplant

Related Stories

Simple steps lengthen lives of high-risk AML patients

December 5, 2016

New research shows that quickly identifying patients with high-risk acute myeloid leukemia (AML), and speeding the process to find them a stem cell donor and performing the transplant earlier, can significantly improve their ...

Immunotherapy shows promise in preventing leukemia relapse

December 6, 2016

Fred Hutchinson Cancer Research Center announced promising results from an early trial in which patients with high-risk acute myeloid leukemia received genetically engineered immune cells. Of the 12 AML patients who received ...

Recommended for you

Artificial beta cells

December 8, 2016

Researchers led by ETH Professor Martin Fussenegger at the Department of Biosystems Science and Engineering (D-BSSE) in Basel have produced artificial beta cells using a straightforward engineering approach.

Key regulator of bone development identified

December 8, 2016

Loss of a key protein leads to defects in skeletal development including reduced bone density and a shortening of the fingers and toes—a condition known as brachydactyly. The discovery was made by researchers at Penn State ...

Researchers question lifelong immunity to toxoplasmosis

December 8, 2016

Medical students are taught that once infected with Toxoplasma gondii—the "cat parasite"—then you're protected from reinfection for the rest of your life. This dogma should be questioned, argue researchers in an Opinion ...

TET proteins drive early neurogenesis

December 7, 2016

The fate of stem cells is determined by series of choices that sequentially narrow their available options until stem cells' offspring have found their station and purpose in the body. Their decisions are guided in part by ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.