Cardiac Muscle Cells Work as Well as Cardiac Progenitor Cells to Repair the Heart


Cell therapies for the heart after a heart attack provide some healing, but the success of these treatments in inconsistent and the majority of the improvements are modest. Whole bone marrow or even bone marrow stem cells can promote the growth of new blood vessels in the heart after a heart attack (Zhou Y, et al., Ann Thorac Surg. 2011 Apr;91(4):1206-12). The treatment of the heart after a heart attack, can also stimulate the regeneration of new heart muscle, but such new muscle comes from endogenous stem cells populations that are induced by the implanted stem cells (Hatzistergos KE, et al., Circ Res. 2010 Oct 1;107(7):913-22).

Nevertheless, the clinical trials with bone marrow cells have produced mixed results. Bone marrow implants work well in some patients and hardly at all in others. The quality of the patient’s bone marrow might be part of the reason for the disparate findings of these trials, but the fact remains, that using cells that can replace dead heart muscle can potentially treat a damaged heart better than bone marrow stem cells.

Pluripotent stem cells, either embryonic stem cells or induced pluripotent stem cells (iPSCs) can efficiently differentiate into heart muscle cells, but a debate remains as to which cell does a better job for healing the heart: Should young heart muscle cells called progenitor cells be used, or can mature heart muscle cells do the job just as well?

Charles Murray from the University of Washington, who has pioneered the use of stem cells to treat the hearts of laboratory animals, and his colleagues tested the ability of heart progenitor cells to repair the heart versus mature heart muscle cells. Both of these cell types were tested against bone marrow stem cells as a control.

Murray and his colleagues used heart muscle cells made from human embryonic stem cells and heart progenitor cells made from the same human embryonic stem cell line to treat the hearts of laboratory rats. These rats were given heart attacks and then the cells were injected directly into the walls of the heart. Injections were given four days after the heart attacks were induced. Each treatment group contained ten rats, including a control group that received injections of cells that are known to possess no healing capabilities.

Measurements of heart function four weeks after treatment showed that both heart progenitor cells and mature heart muscle cells improved the heart equally well and both cells improved heart significantly better than bone marrow stem cells.

Murray said, “There’s no reason to go back to more primitive cells, because they don’t seem to have a practical advantage over more definitive cells types in which the risk for tumor formation is lower.”

In the future, Murry would like to determine if these same cells work in a larger animal model system and then, eventually start clinical trials in human heart attack patients.

Fernandes and Chong et al., Stem Cell Reports, October 2015 DOI: 10.1016/jstemcr.2015.09.011.

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mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).