Transplant Triumph: Cloned Cow kidneys Thrive for Months
On the eve of a U.S. Senate vote that could ban similar experiments in people, scientists have successfully transplanted into cows miniature kidneys and other tissues generated through cloning. The experiments offer the most convincing indication yet that the controversial transplant strategy called therapeutic cloning can produce genetically matched cells that a person's immune system won't reject as foreign.
"This shows that [therapeutic cloning] really does work. That could help shape the debate in Congress," says Robert Lanza of Advanced Cell Technology in Worcester, Mass. He and his colleagues describe their new results in the July Nature Biotechnology.
As envisioned for people, therapeutic cloning would take the DNA of a person needing a transplant and insert it into a woman's egg that had been stripped of its own chromosomes. Scientists would then trigger the egg to start dividing, and they would harvest so-called embryonic stem cells. These immature cells could be transformed, in theory, into any kind of tissue and would almost perfectly match the genetic profile of the intended recipient.
"The ability to generate immunologically compatible tissue using cloning would overcome one of the major scientific challenges in transplantation medicineónamely, the problem of organ and tissue rejection," says Lanza.
Yet there has been a theoretical roadblock to therapeutic cloning. Egg cells have organelles called mitochondria that possess their own snippets of DNA. This mitochondrial DNA, totaling 13 genes in people, remains in the egg when its other DNA is removed. Researchers wondered if proteins produced by the 13 genes could make a person's immune system reject cloned tissue.
"It was a legitimate concern," says study coauthor Anthony Atala of Children's Hospital and Harvard Medical School in Boston.
Earlier this year, another research group used therapeutic cloning to repair the immune system of mice (SN: 3/16/02, p. 163:
At the time, however, Lanza argued that this wasn't a stringent test of the strategy because the animals were inbred and mice don't have as strong an immune system as people do.
Seeking a more formidable challenge, Advanced Cell Technology turned to cows, which have a sophisticated immune system resembling people's. The company's scientists took the DNA from the skin of a Holstein cow and inserted it into egg cells of another Holstein, chosen at random.
Because researchers can't yet derive embryonic stem cells directly from cow eggs growing in a lab dish, as they can from human eggs, they implanted the cow eggs into a surrogate mother and let them develop into fetuses. The team then harvested various kinds of cow fetal tissue, including heart, muscle, and kidney cells. The investigators transplanted this cloned tissue into the cow that had provided the original DNA and saw no sign of immune rejection after 3 months.
The findings "show that even though mitochondrial DNA could potentially make a problem, it doesn't invariably do so," says Kirsten Fischer-Lindhal of the University of Texas Southwestern Medical Center at Dallas, who studies immune reactions to mitochondrial proteins.
Atala notes that the experiments represent more than a success of therapeutic cloning. This is first time, he says, that an artificial kidney fashioned from cells and biocompatible materials has produced what seems to be urine.
Next week, the Senate is expected to debate a bill that could ban both therapeutic cloning and efforts to clone a person.
Lanza, R.P., et al. In press. Generation of histocompatible tissues using nuclear transplantation. Nature Biotechnology. Available at www.nature.com/cgi-taf/DynaPage.taf?file=/nbt/journal/vaop/ncurrent/full/nbt703.html.
Travis, J. 2002. Stem cell success: Mice fuel debate on embryo cloning. Science News 161(March 16):163. Available at /www.sciencenews.org/20020316/fob1.asp.
______. 1999. Lab-grown bladders prove a success in dogs. Science News 155(Feb. 13):101. Available at www.sciencenews.org/sn_arc99/2_13_99/fob4.htm.
Laboratory for Tissue Engineering and Cellular Therapeutics
Harvard Medical School
Boston, MA 02115
Robert P. Lanza
Advanced Cell Technology
Worcester, MA 01605
Kirsten F. Lindahl
University of Texas Southwestern Medical Center, Dallas
5323 Harry Hines Boulevard
Dallas, TX 75390