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Archive - Apr 15, 2013

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Scientists Convert Skin Cells into Functional Brain Cells in Mice

Researchers at Case Western Reserve School of Medicine have discovered a technique that directly converts skin cells to the type of brain cells destroyed in patients with multiple sclerosis (MS), cerebral palsy (CP), and other so-called myelin disorders. This discovery was published online on April 14, 2013 in Nature Biotechnology. This breakthrough now enables "on demand" production of myelinating cells, which provide a vital sheath of insulation that protects neurons and enables the delivery of brain impulses to the rest of the body. In patients with MS, CP, and rare genetic disorders called leukodystrophies, myelinating cells are destroyed and cannot be replaced. The new technique involves directly converting fibroblasts - an abundant structural cell present in the skin and most organs - into oligodendrocytes, the type of cell responsible for myelinating the neurons of the brain. "Its 'cellular alchemy,'" explained Paul Tesar, Ph.D., assistant professor of genetics and genome sciences at Case Western Reserve School of Medicine and senior author of the study. "We are taking a readily accessible and abundant cell and completely switching its identity to become a highly valuable cell for therapy." In a process termed "cellular reprogramming," researchers manipulated the levels of three naturally occurring transcription factors to induce fibroblast cells to become precursors to oligodendrocytes (called oligodendrocyte progenitor cells, or OPCs). Dr. Tesar's team, led by Case Western Reserve researchers and co-first authors Dr. Fadi Najm and Dr. Angela Lager, rapidly generated billions of these induced OPCs (called iOPCs). Even more important, they showed that iOPCs could regenerate new myelin coatings around nerves after being transplanted to mice—a result that offers hope the technique might be used to treat human myelin disorders.

Surprise Finding Could Alter Face of Dengue Vaccine Development

As efforts to create a strong and effective vaccine for the dreaded dengue virus continue to hit snags, a new study from researchers at the La Jolla Institute for Allergy & Immunology offers surprising evidence that suggests the need for a revamped approach to dengue vaccine design. The finding runs counter to current scientific understanding of the key cells that need to be induced to develop a successful dengue vaccine. La Jolla Institute scientist Alessandro Sette, Dr. Biol.Sci., and his team found that T cells, which are key disease-fighting cells of the immune system, play an important protective role in controlling dengue virus infection, rather than creating an aberrant response that can ultimately worsen the disease as is the prevailing belief in the scientific community. "The current thinking in the field is that the goal of a dengue vaccine should be the induction of antibodies and not T cells," says Dr. Sette, an internationally recognized vaccine biologist and director of the Institute's Center for Infectious Disease. "But our results suggest that both cell types are needed to produce a strong immune response against dengue infection." Scott B. Halstead, M.D., a leading authority on dengue virus and senior scientific advisor to the international Dengue Vaccine Initiative, says the findings provide new insights that should be considered in future dengue vaccine efforts. "Their study of T cell responses in a large group of HLA-defined Sri Lankan adults naturally infected by dengue viruses found that T cell immunity contributed to host protection rather than to vascular permeability (which occurs in severe cases)," says Dr. Halstead.

Scientists Develop Functional, Implantable, Bioengineered Rat Kidney

Bioengineered rat kidneys developed by Massachusetts General Hospital (MGH) investigators successfully produced urine both in a laboratory apparatus and after being transplanted into living animals. In their report, receiving advance online publication on April 14, 2013 in Nature Medicine, the research team describes building functional replacement kidneys on the structure of donor organs from which living cells had been stripped, an approach previously used to create bioartificial hearts, lungs, and livers. "What is unique about this approach is that the native organ's architecture is preserved, so that the resulting graft can be transplanted just like a donor kidney and connected to the recipient's vascular and urinary systems," says Harald Ott, M.D., Ph.D., of the MGH Center for Regenerative Medicine, senior author of the Nature Medicine article. "If this technology can be scaled to human-sized grafts, patients suffering from renal failure who are currently waiting for donor kidneys or who are not transplant candidates could theoretically receive new organs derived from their own cells." Approximately18,000 kidney transplants are performed in the U.S. each year, but 100,000 Americans with end-stage kidney disease are still waiting for a donor organ. Even those fortunate enough to receive a transplant face a lifetime of immunosuppressive drugs, which pose many health risks and cannot totally eliminate the incidence of eventual organ rejection. The approach used in this study to engineer donor organs, based on a technology that Dr.