New cardiac progenitor cells found in the hearts of neonate humans, rats, and mice provide evidence of the heart’s regenerative potential. The discovery was reported in the February 10 issue of Nature by a multi-institution group of US and German researchers (Laugwitz et al. Nature. 2005;433:647-653). According to the report, the cells are precursors of cardiac muscle cells that can be multiplied into millions of cells in vitro. These cells also appear to form fully differentiated functioning cardiac muscle cells in the presence of other heart cells. Human cardiac progenitor cells (arrowheads) were found in a part of the atrial septum that is routinely discarded during surgeries to correct heart defects in neonates. (Photo credit: Peter J. Gruber, MD, PhD.) Previous studies have identified cardiac stem cells and cardiac precursor cells in humans (Beltrami et al. Cell. 2003;114:763-776, Messina et al. Circ Res. 2004;95:911-921). Attempts to translate these findings into clinical trials that deliver stem cells from bone marrow to treat heart disease have had limited success so far and the ultimate therapeutic value remains unclear. Cells of adaptation Cells of adaptation Kenneth Chien, MD, PhD, the director of the University of California at San Diego Institute of Molecular Medicine, noted that the newly identified cells are distinct because they have a unique developmental origin. The cells were found on the right side of the heart, which normally experiences dramatic changes in hemodynamic loading conditions immediately after birth. He said he believes these cells play an important role in enabling this adaptive process to proceed quickly and smoothly. Cells of adaptation Jonathan Epstein, MD, a professor of medicine and cell and developmental biology at the University of Pennsylvania, in Philadelphia, said advances in the understanding of heart development in the past 3 years have laid the groundwork for this discovery. Cells of adaptation “This population of progenitor cells was identified based on a sound, recent, fundamental understanding of how the heart normally develops,” said Epstein, who coauthored a mini review of research into cardiac progenitor cells (Parmacek and Epstein. Cell. 2005;120:295-298). “There’s a good scientific basis for why these cells might really exist.” Cells of adaptation Epstein said the study details the progenitor cells’ behavior in culture. “They obey properties that we would expect from real cardiac myocytes,” he noted. Cells of adaptation Mark Keating, MD, a professor of cell biology and pediatrics at Children’s Hospital Boston, said the newly identified cells comprise the fourth subset of progenitor or stem cells that have been identified in the heart, suggesting “there is heterogeneity in the heart.” Cells of adaptation Because of their distinctive right-sided developmental origins, these cells are more efficient in developing into cardiac muscle cells than are pluripotent stem cells, with about 30% of the cells becoming beating heart muscle cells, Chien said. Cells of adaptation “It’s not like a totipotent stem cell that is making a decision to go down a specific pathway because you are coercing it,” he explained. “These cells are programmed and groomed to go in this direction.” Congenital heart disease Congenital heart disease The researchers identified progenitor cells on a portion of the atrium that is routinely discarded during surgery, in tissue collected from five human neonates who had undergone emergency heart surgery. Chien said the finding suggests that it may be possible to identify the molecular basis for congenital heart defects or, conceptually, to grow progenitor cells that could be used as a cell-based therapy to treat such defects. Congenital heart disease “It represents a new way to think about congenital heart disease, not just as a defect in the gene or in the structure, but actually as a defect within these progenitors,” Chien said. Congenital heart disease Other researchers, however, are less convinced that the finding has clinical implications for treating congenital heart problems. Keating, whose own research focuses on targeting therapies to regenerative cells rather than using the cells as a treatment, said that while the current study identifies yet another potential therapeutic target, the discovery is just a small step with no near-term translation to the clinic. Congenital heart disease Epstein said the finding’s real clinical implications are for treating adult heart disease, such as reduced cardiac function following a large myocardial infarction. But fundamental questions remain, he cautioned. These include, for example, the mystery of why, with the existence of so many different types of progenitor cells in the adult heart, there is still no evidence that the human heart is able to regenerate new tissue when it is damaged. Congenital heart disease Moreover, “it remains to be proven that we can isolate progenitors that we can grow in the laboratory and deliver back to the heart and have them actually contribute to the function,” Epstein added. Congenital heart disease In the near term, however, Chien hopes the cells will provide a tool for studying cardiac muscle cells in vitro or for testing drugs.
JAMA – American Medical Association
Published: Mar 23, 2005
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