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t m c » p u l s e | j a n / f e b 2 0 1 5 19 "Decellularization is very simple," she explained. "It's essentially just washing out the cells. You have something that goes from a red, muscularized organ to an acellularized construct over a relatively short period of time, while leaving the extracellular matrix composition intact—it literally looks like you took a tube of toothpaste and squeezed. What's left is the structural composition. "We have the ability to recapitulate a whole heart," she added. "We determined that we could take one of these decellularized hearts and simply put cells back into the vascular tree to recellularize the whole network." Taylor is driven to ultimately reseed hearts using cells from a given individual to manufacture an available, tailor-made organ for transplantation. Researchers at Texas Heart Institute aren't the only ones vying for new ways to regenerate damaged tissue. At the Houston Methodist DeBakey Heart & Vascular Center, cardiovascular scientists are explor- ing a medical approach for transforming human heart cells into blood vessel cells. "This approach, known as transdifferentiation, actually avoids cell-based therapy entirely," said Cooke. "In a situation where you have an injury, a small molecule cocktail could potentially transdiffer- entiate some of those cardiac fibroblasts—a cell type that causes scarring and is plentiful throughout the body—into endothelium, an entirely different type of adult cell that forms the lining of new blood vessels." Chronicled in a recent issue of Circulation, this method provides proof-of-concept for a small mole- cule therapy that could one day be used to improve healing of cardiovascular damage or other injuries. "What we've discovered is something that lower vertebrates use to regenerate tissues, where their cells become more plastic in their phenotypes," said Cooke. "It's a very primordial response—once a cell is con- fronted by damage or a pathogen, it has to react and change its phenotype to become more fluid. Now that we understand this phenomenon, we're looking at the potential in manipulating that, therapeutically." Leveraging the plasticity of certain types of cells is also within the purview of immunologists at Baylor College of Medicine, who are invested in harnessing the immune system to treat cancer. "The crux of our work has less to do with regen- erative medicine and more to do with the plasticity of blood stem cells and how they can be harvested in treating disease," explained William K. Decker, Ph.D., assistant professor of immunology at Baylor. "Immune cells are even more plastic than people realize. When they're stimulated in different ways, they really have this tremendous differentiative potential and can turn into highly specialized subtypes for addressing various kinds of immunological conditions. "We're really interested in generating these highly specific, cancer-fighting immune cells from regular immune cells," he continued. "We study the signals required to turn ordinary cells into these super, cancer-fighting immune cells, and we're interested in a broad variety of cancers." A process that uses the body's own immune system to treat cancer instead of relying on external treatments like chemotherapy, cancer immunotherapy may have the ability to stave off metastasis, while also offering a reduced side effect profile. Decker and his colleagues hope to train the immune system to recognize cancer, preventing it from returning after it has been eradicated. "People will still need chemotherapy and radio- therapy, but hopefully the doses can be smaller and the side effects more manageable," he said. "We envi- sion this working in a way that prevents subsequent metastasis, so that it might have a real impact on both relative and absolute longevity." At UTHealth Medical School, stem cell research is being used as an innovative approach to treat trau- matic brain injury in children. "One of the critical unmet needs in pediatric care is the lack of a reparative therapy for traumatic brain injury—that's really where I first became engaged in the use of stem cell based therapies," reflected Charles Cox, Jr., M.D., professor of pediatric surgery and direc- tor of the Pediatric Surgical Translational Laboratories and Pediatric Program in Regenerative Medicine at UTHealth Medical School. "The development of the Pediatric Program in Regenerative Medicine came out of that unmet need." Cox, who also directs the Pediatric Trauma Program at Children's Memorial Hermann Hospital, aims to address problems that originate with a severe traumatic injury—the ones resulting in coma and plac- ing the young trauma victims at risk for permanent disability. To mitigate that risk, he recently completed the first acute autologous cell therapy treatment for traumatic brain injury. The applications of stem cell therapy in neurological injuries or disorders are extensive—Sean Savitz, M.D., professor of neurology at UTHealth Medical School, and his research teams have realized that adult derived stem cells from a patient's own bone marrow have the capacity to enhance recovery following a stroke. "We started looking at mechanisms for that repar- ative potential and found that the cells are potentially releasing a number of biological factors that help the brain heal itself," Savitz explained. "It became a very different approach to how we think stem cells function." In July 2011, the first patient in Texas was enrolled in the country's first double-blind clinical trial studying the safety and efficacy of a stem cell therapy technique that can be given up to 19 days after an ischemic stroke. Savitz believes that expanding the time window for administering stem cells increases the number of patients who might be helped. "I see really high potential for developing cell ther- apies for a range of neurological disorders," he added. "I think that's partly a goal here, thinking about which disorders might be amenable in using cell therapies and doing properly designed, rigorous clinical trials to assess their safety and effectiveness. I don't think the way that cell therapies are being applied is going to completely cure neurological disease, but I think some of them have the potential to slow down the course of neurodegenerative disorders." Rebuffing misconceptions is an essential aspect of any burgeoning discipline. At Rice University's Baker Institute for Public Policy, Kirstin R.W. Matthews, Ph.D., the fellow in science and technology policy, wanted to explore those dynamics. "My research focuses on ethical and policy issues related to biomedical research and development," she said. "Specifically, I am looking at intellectual property rights for biotechnology, including genetics and stem cell related patents. Initially, when all of these deci- sions were being made, it seemed like they were occa- sionally being politically manipulated—often due to a lack of understanding of the science behind them." In a recent paper that she co-authored with Maude Rowland Cuchiara, Ph.D., the Baker Institute scholar for science and technology policy, Matthews examined how some National Football League (NFL) players have been seeking out unproven stem cell therapies to help accelerate recoveries from injuries. While most players seem to receive treatment within the United States, several have traveled abroad for therapies unavailable domestically and may be unaware of the risks. "With the rise of new and unproven stem cell treatments, the NFL faces a daunting task of trying to better understand and regulate the use of these thera- pies in order to protect the health of its players," said Matthews. "The online data on NFL players and the clinics where they obtained treatment suggests that players may be unaware of the risks they are taking. Furthermore, players who are official spokespersons for these clinics could influence others to view the therapies as safe and effective despite the lack of scientific research to support these claims." Her paper was published in the 2014 World Stem Cell Report—a special supplement to the journal Stem Cells and Development. This past year, the Summit was held in San Antonio, Texas. Matthews, Cox, Decker, Cooke, Taylor, and Willerson all gave presentations illustrating highlights of their work in regenerative medicine. "There are multiple ways that these advances in regenerative medicine can change the landscape of health sciences," affirmed Taylor. "I see regenerative medicine providing hope for people who haven't had hope for years, as well as alternatives—not just to treat the symptoms but to treat the underlying disease. That way, we can actually move people backwards on the disease continuum rather than simply palliating their symptoms. "I truly hope participants at the World Stem Cell Summit walked away realizing that Texas is a place where, if you can imagine it, you can do it," she added. "It's not crazy to have a Stem Cell Summit in the mid- dle of Texas. It's actually very progressive, because we have some of the best thinkers in the world here." Our goal is the regeneration of the whole heart, or at least enough of it so that a very weak heart would be made anew. JAMES T. WILLERSON, M.D. President of Texas Heart Institute