Importantly, regeneration of heart tissue in the mice was achieved without the use of drugs, transferred cells or tissues, such as stem cells, or any other intervention. The observed healing is a native capacity of this particular strain of mice.
"In these adult mice, cells in the region of an injury to the heart tissue were replaced over time by new cells that were indistinguishable from neighboring healthy heart cells," says Ellen Heber-Katz, Ph.D., a professor at The Wistar Institute and senior author on the study. "After two months, the damaged heart tissue looked normal and functioned well."
The degree of tissue renewal seen in the MRL mice is strikingly atypical of mammalian heart tissue. Similar injuries to the heart tissue of control mice, for example, showed that only 1 to 3 percent of the heart cells in the region of the injury were capable of dividing. In the MRL mice, however, up to 20 percent of the heart cells divided in response to injury.
The only species known to demonstrate similar capacities for regeneration are non-mammalian species - certain reptiles and amphibians - able to replace limbs and other body parts.
"In more than 15 years of investigations involving muscle tissue, I'd never seen anything like this," says John M. Leferovich, first author on the study. "The observation was quite stunning."
The current study follows on observations of the remarkable regenerative powers of the MRL mice first published by Heber-Katz and her coworkers in 1998. At that time, they noted the mice were able to heal small holes punched in their ears for identification purposes, with little or no evidence of scarring.
The research is now moving in the direction of identifying specific genetic and molecular differences between the MRL and other mouse strains. Such differences may ultimately lead to the identification of candidate drug compounds for improved healing in a broad array of injuries and disease.
In addition to first author Leferovich and senior author Heber-Katz, the other Wistar authors on the study are Khamilia Bedelbaeva, Stefan Samulewicz, and Xiang-Ming Zhang. Authors Donna Zwas, M.D., and Edward B. Lankford, M.D., Ph.D., with the Division of Cardiovascular Medicine at Thomas Jefferson University in Philadelphia, performed the functional studies.
The research has been generously funded from its inception by the G. Harold and Leila Y. Mathers Charitable Foundation, a private foundation based in Mount Kisco, NY. Recently, the work has also received substantial funding from the F.M. Kirby Foundation in Morristown, NJ, and the National Institutes of Health.
The Wistar Institute is an independent nonprofit research institution dedicated to discovering the causes and cures for major diseases, including cancer and AIDS. The Institute is a National Cancer Institute-designated Cancer Center - one of the nation's first, funded continuously since 1968, and one of only 10 focused on basic research. Founded in 1892, Wistar was the first independent institution devoted to medical research and training in the nation. Since the Institute's inception, Wistar scientists have helped to improve world health through the development of vaccines against rabies, rubella, rotavirus, and cytomegalovirus and the identification of genes associated with breast, lung, prostate and other cancers.
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