Cell Therapy Hinges on Beating Rejection
Researchers agree that the future of stem-cell therapy depends to a large degree on preventing the recipient’s immune system from rejecting transplanted tissue.
But how? Using a patient’s own cells to create a cloned embryo and deriving transplantable tissue from the embryo’s stem cells might solve the problem, questions about its cost-effectiveness notwithstanding. But some researchers caution that the theoretical benefits of this therapeutic cloning approach may never materialize and say a bevy of other tactics may eventually beat the rejection problem.
“We can probably find a way around it, perhaps by doing immunosuppression for a while if need be,” said Dr. Wise Young, director of Rutgers’ W.M. Keck Center for Collaborative Neuroscience. “On the other hand, I think there is some value in cloning, because theoretically, cloning does give you the best transplant material.”
Researchers at Advanced Cell Technology in Worcester, Mass., are banking on that potential. Scientists there created a furor when they announced earlier this month that they added genetic material to donated eggs devoid of their own DNA and coaxed one of the cloned human embryos to the six-cell stage before it died.
Dr. Robert Lanza, the vice president of medical and scientific development for Advanced Cell Technology, said in a telephone interview that his company has transplanted stem cell-derived tissue such as myocardial patches into cows and demonstrated immune system evasion three to six weeks after implantation.
But critics say the picture is far from complete.
“Part of the issue is that nobody has really looked long term in terms of rejection of transplants,” Young said. “Most people look maybe six weeks in animals. I think that if there were rejection occasionally, the data that we currently have would not show it, because we’re not looking long enough.”
Chimeric Therapies of Laguna Niguel is working on a possible solution that would create immune systems in transplant patients derived from both the donor and recipient. Under such a scenario, researchers would first perform a bone-marrow stem cell transplant, wait several months for the new chimeric immune system to take hold, and then follow with the stem cell therapy of interest.
At a San Diego-based stem cell research company called CyThera, scientists are deriving pancreatic islet cells from human embryonic stem cells to treat diabetes. Studies in mice suggest that pancreatic islet cells don’t induce an immune response at all.
“If that is true in humans, then we don’t have to immune-suppress,” said Lutz Giebel, CyThera’s chief operating officer and founder. If not, researchers could try agents that prevent the immune system from recognizing the cells, such as humanized monoclonal antibodies that interfere with immune cell interactions. Whether such treatment would be lifelong is still an “open question,” Giebel said.
But anecdotal reports of isolated organ transplants suggest that rejection is not always a foregone conclusion in the absence of immune suppression. And other studies have shown that this therapy need not be maintained forever after a transplant.
Menlo Park, Calif.-based Geron Corp. is taking a different tack by trying to understand the molecular biology of cloning and determining which proteins act to reset the cellular clock. Harnessing such factors could eventually transform a patient’s skin cells into all or most of the more than 200 other specialized cells in the human body, thus avoiding immune system rejection, said Dr. Thomas Okarma, Geron’s president and chief executive. “So we do think we agree with [Advanced Cell Technology] on the desire to create transplantable cells that won’t be rejected,” he said, “but we vehemently disagree with the way to get there.”
And scientists have plenty of other approaches to try. “You can actually take your human embryonic stem cells and get rid of the genes that display their antigens recognized by the immune system,” Giebel said. “That’s the Holy Grail of human embryonic stem cell research.”
