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Artificial Thymus Could Enhance Bone Marrow Transplantation   
 
 
By Hooman Dilmanian
 

In what could prove to be a major boon for the field of bone marrow transplantation, scientists at Harvard Medical School have created an artificial version of the thymus, an organ involved in the development of a key arm of the body’s immune system.

The artificial thymus, termed an organoid, was made by planting cells taken from the thymuses of mice onto an elaborate three-dimensional scaffold shaped somewhat like the real organ. The new thymus successfully generated fully functional disease-fighting cells called T cells, just as a natural thymus does inside the body.

 
Courtesy of Cytomatrix.
The findings appear in the July 2000 issue of Nature Biotechnology.

In certain cancers of blood cells like leukemia, patients often receive transplants of T cell-containing bone marrow from healthy donors to replace diseased cells. The T cells, which are mostly undeveloped, can take months or even years to become fully functional. In the meantime, the marrow recipients, whose diseased cells have been largely wiped out by chemotherapy and radiation, are left vulnerable to life-threatening infections and other complications.

“Perhaps the most immediate application [of the artificial thymus] will be generation of T cells to enhance immune reconstitution after [bone marrow] transplantation,” wrote David L. Porter, M.D., and Stephen G. Emerson, M.D., of the University of Pennsylvania, in an accompanying commentary on the new findings. “A tissue-engineered thymic organoid that could continuously generate mature T cells could potentially overcome major obstacles to [transplantation] therapy.”

Successes Range From Artificial Thymus to Ears

The artificial thymus is the latest in a series of advances in the field of tissue engineering, in which scientists try to repair damaged or diseased body parts or to replace them altogether with artificial tissue or organs that are at least partly grown outside the body. Recent successes have included artificial bladders for dogs, blood vessels for pigs and human ears grown on the backs of mice.

In one approach to tissue engineering, a three-dimensional scaffold is constructed from a computer model of the organ of interest that simulates the spatial arrangement of cells in the real thing. The scaffold is filled with microscopic pores where cells from a healthy organ are planted. The cells then divide and grow just as they would in the organ inside the body.


Artificial Thymus Could Enhance Bone Marrow Transplantation
 
 
POSTED 06.28.2000
By Hooman Dilmanian
 


The scaffold is ideally made from a material that is tolerated by the body’s immune system and that gradually degrades inside the body, leaving behind the new organ.

Now, researchers led by Mark C. Poznansky, Ph.D., of Massachusetts General Hospital in Boston have applied tissue engineering to the thymus, a small gland located high in the chest that serves as a kind of immune system “training camp” where immature blood cells from the bone marrow develop into T (for “thymus”) cells, ready to attack any cells that look “foreign.”

The thymus scaffold used by Poznansky’s group was made from CellFoam, a porous, metal-coated carbon matrix that is being developed by Cytomatrix Corporation of Woburn, Mass. The pores were planted with cells taken from the thymuses of mice. The planted scaffold was then treated with the immature blood cells taken from human bone marrow.

New Thymus Could Mean Better Treatment, Safer Transplant

Within two weeks, the resulting artificial organ was producing large quantities of fully functional T cells that could target a wide variety of foreign-looking cells. According to Emerson, a major advantage of using an artificial thymus to produce T cells in this way is that it can generate T cells that specifically target just one kind of cell.

As an example, the planted scaffold used to grow the organoid could be treated with leukemia-specific proteins. The T cells produced by the resulting organoid would then be targeted exclusively to leukemia cells. When given to a leukemia patient, these T cells should help destroy diseased cells.

Another potential application, noted Irwin Bernstein, M.D., of the Fred Hutchinson Cancer Research Center in Seattle, would be to plant the scaffold with healthy cells from the patient receiving the transplant. Any T cells that reacted to the human cells would be inactivated. The remaining T cells, when transplanted, would not attack the recipient own’s tissue, unlike those from an unrelated donor.

The technology, said Bernstein, “opens up a whole new area of research.”

Mark Pykett, president of Cytomatrix, noted that the CellFoam technology was also being used to make stem cells, the precursors to the entire range of blood-cell types. When used in transplants, these stem cells could give rise to T cells, as well as the other cells.

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