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1st evidence that nuclear transplantation (’therapeutic cloning’) can eliminate tissue rejection


Heart ’patches’ and functioning kidney units cloned in cows

Advanced Cell Technology, Inc. (ACT) reported today that nuclear transplantation can be used to generate functional immune-compatible tissues. The research, which will appear in the July issue (cover story) of Nature Biotechnology, by ACT and its collaborators, provides the first experimental evidence that it may be possible to use cloning to generate medically important tissues and eliminate tissue rejection. Heart ’patches’ and miniature kidneys engineered from cloned cells were successfully tested in a large-animal model, the cow, which has a sophisticated immune system similar to that of humans.
"These results bode well for the future of human therapeutic cloning," said Robert Lanza, Vice President of Medical & Scientific Development at ACT, and lead author of the study. "Cloning could theoretically provide a limitless supply of cells and organs for any type of regenerative therapy. Before now, therapeutic cloning as a means of preventing rejection was criticized by some as being purely theoretical – just an idea. This study furnishes the first scientific evidence that cloned tissues can be transplanted back into animals without being destroyed by the body’s immune system. The use in medicine to generate immune-compatible cells using cloning would overcome one of the major scientific challenges in transplantation medicine - namely, the problem of organ and tissue rejection."

The goal of nuclear transplantation is to clone genetically matched cells and organs for transplantation into patients suffering from a wide range of disorders that result from tissue loss or dysfunction. In addition to patients with heart, lung, liver and/or kidney disease, millions more suffer from diabetes, arthritis, AIDS, strokes, cancer and other diseases that may one day be treatable using this technology. It has been estimated that by the year 2010 over 2 million patients will suffer from end-stage kidney disease alone, at an aggregate cost of over $1 trillion dollars during the coming decade.

Although nuclear transplantation could theoretically be used to generate immune-compatible cells and tissues for these patients, numerous studies have shown that animals produced by cloning inherit the DNA in their mitochondria (the organelles that supply energy to the cell) entirely or in part from the recipient egg and not the donor cell. The presence of these foreign genes raises the question whether ’non-self’ proteins in cloned cells could lead to rejection after transplantation and defeat the main objective of the procedure. The Nature Biotechnology paper reports that cloned cells were not rejected in cattle despite the presence of the foreign mitochondrial DNA. The immune system in cattle is relatively complex; therefore, these "preclinical" studies suggest human applications may be possible.

In addition to creating skeletal muscle and heart ’patches,’ nuclear transplantation was used to generate immune-compatible kidney units with the ability to excrete toxic metabolic waste products through a urinelike fluid. The renal units not only survived and functioned as kidneys, but immunological studies carried out both in the transplanted animals and in the laboratory confirmed that there was no rejection response to the cloned tissues.

"This was a study to investigate how the immune system would deal with cloned tissue in an animal model," said Michael D. West, President & C.E.O. at ACT and an author on the paper. "In such an animal model, we judged it appropriate to produce cloned bovine fetuses to generate the needed cells. In the case of human medical applications, we are strongly advocating that the technology should only be used to clone human embryonic stem cells not an actual pregnancy. We, therefore, strongly support Senate Bill S. 2439 promoted by Senators Kennedy, Feinstein, Hatch and Specter that would protect the life-saving uses of cloning technology while banning its abuse in cloning a human fetus or child."

The researchers of the paper from Advanced Cell Technology, collaborated with scientists from Harvard Medical School and Children’s Hospital, Boston; the Mayo Clinic, Rochester, Minnesota; and the University of Miami School of Medicine, Miami, Florida. The paper’s other authors are Catherine Blackwell of ACT; Anthony Atala, Hoyun Chung, James J. Yoo, Gunter Schuch, and Shay Soker of Children’s Hospital; Peter J. Wettstein, Nancy Borson, and Erik Hofmeister of the Mayo Clinic; and Carlos T. Moraes of the University of Miami School of Medicine.

Advanced Cell Technology is a biotechnology company focused on discovering and commercializing the applications of cloning technology in human medicine and animal science.

Robert Lanza | EurekAlert
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