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"The most exciting prospect is we can make virtually unlimited supplies of genetically matched stem cells and convert these into large amounts of cartilage, for either therapeutic application or drug screening. That's a real breakthrough. We can make osteoarthritis in a dish, which will allow us to come up with a new therapy that has eluded us for decades because we didn't have the means to screen drugs without performing animal studies." — Farshid Guilak, Ph.D., professor of orthopedic surgery at Duke university Medical Center patients who have specific risk factors of specific diseases," Dr. Guilak says. "Then, knowing the genetic background of each sample, we can perform large-scale screenings of medications that affect the disease." make your Own bone Similarly based upon iPS cell engineering, a team led by Gordana Vunjak-Novakovic, Ph.D., Mikati Foundation Professor of Biomedical Engineering, professor of medical sciences and Director of the Laboratory for Stem Cells and Tissue Engineering at the Fu Foundation School of Engineering and Applied Science at Columbia University, has engineered a full-sized pig temporomandibular joint (TMJ). Using a process lasting approximately three to five weeks, Dr. Vunjak-Novakovic's team has engineered multiple bones, but the TMJ required the most skill because of its function and complexity. "We picked the most difficult bone to make so if it were not made properly, it would break," Dr. Vunjak-Novakovic explains. "It has to be structurally and compositionally similar to bone and be able to integrate with the host bone, but it also needs to withstand loading, which is significant because it's associated with chewing." Growing bone requires a high degree of specificity, especially because future implications will likely require not only full bone replacements, but also partial replacement pieces. Using computed tomography (CT) imaging, researchers constructed a scaffold upon which the engineered bone would grow. For bone to grow properly, the scaffold, which can be made synthetically or from native bone, must be both microscopically and macroscopically identical to the bone being replaced. This means creating pores and channels through which nutrients flow and exactly replicating the bone's size and shape. After cells are placed on the scaffold, the scaffold enters a bioreactor, which replicates the bone-forming environment in the body. When researchers extract the scaffold from the bioreactor, the bone is not fully mature, but Dr. Vunjak-Novakovic says this is ideal. "For any engineered tissue, you don't want immature, weak bones. You also don't want completely formed bone," explains Dr. Vunjak-Novakovic. "If we had the ability to make bones equivalent to adult human bones, that would be great for bearing mechanical loading, but it wouldn't be good for integrational bonding with the host bone because the only mechanism by which implanted tissues bond or integrate to the host tissues is their development." game-Changing implications This new technology avoids the ethical dilemma of using embryonic stem cells, which typically do not genetically match host cells. Because iPS cells are harvested from patients, the risks of host rejection or disease transmission are reduced. Dr. Guilak notes that iPS cell engineering will provide physicians a bank of specimens from specific individuals whose risk factors and genetic makeups differ, allowing a tailored approach to both therapeutic and pharmacologic treatments. ■ b u i ldi n g o n a Fi r M Fo u n dati o n RESEaRCHERS uSing adult stem cells cells. in 2007, Dr. yamanaka announced he for transplantation or drug efficacy had replicated the success of his animal trials and safety trials are indebted to in human studies. shinya yamanaka, M.D., Ph.D., senior iPs cells allow researchers to engineer investigator at the Gladstone institute patient-specific stem cells from adult stem of Cardiovascular Disease, L.K. Whittier cells harvested from blood, skin, fat or foundation investigator in stem cell biology bone marrow, avoiding the need to harvest and professor of anatomy at the university embryonic stem cells. of California, san francisco. Dr. yamanaka, in a statement, Dr. yamanaka explains winner of the 2012 nobel Prize in Physiology why the nobel Prize is important to stem or Medicine, devised a way to transform adult cell research. skin cells into cells that can change into any "the best part about this prize is that kind of human anatomical cell, much like it will bring attention to — and will likely embryonic stem cells. spur — the important stem cell work that Lab experiments on mice conducted in scientists around the world are conducting," 2006 yielded Dr. yamanaka's discovery Dr. yamanaka says. "this iPs technology is that he could make adult stem cells act as for patients, and the more scientists who embryonic stem cells by adding four genes. build on it, the faster we can help those who He called them induced pluripotent (iPs) live with chronic or life-threatening diseases." mdnEwS.COm ■ MD News Greater Boston | 13

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