With lots of help from stem cells, tissue engineering and regeneration is growing up fast. Tissue-engineered skin and cartilage are already here, and starting next year replacement bladders engineered from adult stem cells will likely join them. Windpipes engineered from adult stem cells have cured lamb fetuses of windpipe defects from which they might otherwise have died after birth, and a simple method of generating new bone within a patient’s own body for transplant to another site within it has the potential to become a staple of orthopedics.
But if there is ever to be a universal and ultimate form of tissue and organ engineering, and a panacea for all ills, this is probably it, and it may be within reach: A strain of experimental mice has the ability to regenerate whole limbs and organs if they are damaged or even lost, and it is possible we share with those mice the genes responsible for this ability. Even if we don’t, we will probably be able to engineer them. |
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Growing A Bladder
Investors who recently put US$39 million* into start-up Tengion Inc. evidently believe it can deliver on its promise to “grow” new bladders using patients’ own cells, notes a report in the Philadelphia Inquirer. And with some justification: The technology is based on 15 years of research and 70 patents licensed from Children’s Hospital of Boston and the Massachusetts Institute of Technology. The method has yet to be tested in humans, but will involve selecting healthy progenitor cells from a small biopsy of a patient’s diseased bladder, cultivating their growth in vitro, then attaching them to a biodegradable bladder-shaped scaffold that is then implanted in the patient, where it will mature into a fully functioning bladder. The scaffold will by then have dissolved. The company is planning a clinical trial of a bladder in children with spina bifida in 2006 and additional trials in adults and more children after that. FDA approval could be won by 2009. Over 15 years-worth of large-animal studies have demonstrated that such bladders are safe and effective over the long term, but “you never know until you actually get it in patients,” said the lead researcher. If it works, however, “The bladder is just a start,” the company’s chief financial officer said. * Just for comparison: This is $4 million more than the Pentagon plans to spend over the next four years on prosthetics research for disabled servicemen and women. Stem Cells Engineered for Fetal Surgery A team at the Children’s Hospital of Boston used mesenchymal stem cells from amniotic fluid to grow sections of cartilage tube, which were then implanted into seven unborn lambs still in their mothers’ wombs to repair windpipe defects. The cells were cultured in the lab, “seeded” onto biodegradable tubes and exposed to growth factors to stimulate them to differentiate into cartilage tissue. Of five lambs that survived to term, all were able to breathe spontaneously at birth and four showed no sign of respiratory distress. The lead researcher has applied to the US Food and Drug Administration for permission to grow grafts from cells taken from human amniotic fluid. “Theoretically, someone with a broken back can have new bone grown in his leg and then transplanted to the fracture site so that the body can mend itself,” says an article in The Tennessean describing the promising results of international research into growing new, natural, bone in one part of the body for transplant into another part that needs it. It would be useful for spinal fusion patients, since a hip graft to harvest bone for the fusion procedure — and its accompanying long-lasting pain — could be avoided. The method has been successfully tested in rabbits, and human clinical trials could begin in Europe “within the next six months or so.” It is fairly simple: under the hard outer layer of long bones such as the shins is a layer of cells that have the ability to grow into mature bone. Saline solution in injected into this layer through a pinhole, expanding it like a balloon and leaving more space for the cells to replicate and mature. A calcium gel “bone bioreactor” is also injected into the space, and “At four weeks you look into the bioreactor space and you’ve got beautiful bone,” a researcher told The Tennessean. Before it can fuse within the bioreactor, the new bone is removed and transplanted to the fracture site. The body accepts the grafted bone as its own and sends out blood vessels and nerves to seamlessly connect the old bone to the new. US researchers serendipitously discovered that a strain of experimental mice known as MRL had the ability to regrow at least their heart, toes (complete with joints), optic nerve, liver, and tail, according to an article in The Australian. When fetal liver cells from the test mice were injected into ordinary mice, they too acquired the ability to regenerate. The research, conducted at the Wistar Institute, has pinpointed about a dozen genes as being behind the ability. Though the genes’ exact functions are not yet known, humans are thought to have comparable genes, which would make regeneration possible for humans also. The lead researcher said: “We have experimented with amputating or damaging several different organs, such as the heart, toes, tail and ears, and just watched them regrow. It is quite remarkable. The only organ that did not grow back was the brain.” The power of regeneration persisted “even six months after the injection.” The researchers believe the same genes could also confer greater longevity and are measuring their animals’ survival rate. |