Exosomes released from stem cell patches shown to treat heart attack damage

Human heart muscle patches made from stem cells helped fix damage and improve heart functions in tests with pigs induced with heart attacks. A team at University of Alabama in Birmingham describes the patch and findings from the tests in yesterday’s issue of the journal Circulation (paid subscription required).

Researchers led by Jianyi “Jay” Zhang, chair of the university’s biomedical engineering department, are seeking better treatments for heart attacks that damage heart muscle tissue, which does not regenerate on its own. A heart attack occurs when oxygen and nutrients supplied to heart muscles in coronary arteries are reduced or cut off, such as from blood clots that form around the build-up of plaques in the arteries. When starved for oxygen and nutrients, heart muscles become damaged or die, causing a life-threatening condition. American Heart Association says a heart attack occurs about every 40 seconds in the U.S.

Earlier attempts to grow heart muscle tissue from stem cells either injected into the affected area or grown on thin films, say the authors, so far resulted in low rates of survival or grafting to the damaged muscle. The team set out to create a three-dimensional patch with the types of cells needed to regrow new heart muscle. Those cells include cardiomyocytes or heart-muscle cells, endothelial cells that line blood vessels, and smooth muscle cells. All of the cells were derived from human induced pluripotent stem cells, so-called adult stem cells taken from skin and other tissue.

The stem cells are seeded on a matrix made from fibrin, a fibrous protein that helps blood coagulate and form clots to stop bleeding. To help the stem cells transform into heart muscle cells and tissue, the matrices are continuously rocked back and forth in growth cultures for a week; see image at top. The authors attribute the rocking motion to producing patches that perform physiologically and contract more like real heart tissue than previous attempts. The patches measure 40 x 20 millimeters, with a thickness of 1.25 millimeters, about the same thickness as a U.S. dime.

The researchers implanted 2 stem-cell derived heart muscle patches in 13 pigs induced with heart attacks. Pigs have organs similar in size and function as humans. For comparison, other pigs with similar heart damage were implanted with fibrin patches without stem cells, subjected to a sham surgery, or were untreated. The team measured cardiac functions with MRI scans, and tracked rates of grafting to the damaged area, heart rhythms, and expression of cardiac proteins indicating release of exosomes from the patches.

Exosomes are tiny lipid-membrane containers in cells that gather up and secrete cytoplasm, the gel-like material outside the cell nucleus. While originally believed to carry out waste removal and other maintenance tasks, exosomes were shown in recent years to perform useful delivery functions carrying proteins and genetic material to other cells.

The results show about 11 percent of the patches graft to the heart damage after about a month, considered a high rate of attachment for these devices. Pigs with the full patches show greater functioning of the left ventricle in the heart that pumps blood through the aorta, the body’s main artery. The pigs with the full patches also show less heart muscle damage, stress on the heart wall, heart enlargement, and cell death than untreated pigs or those with unseeded patches. In addition, analysis of the cardiac proteins suggest the exosomes released by the patches protect heart muscle cells as they become contracting muscle tissue.

Heart muscle patches are not the only technology being created to treat damage from heart attacks. As reported in Science & Enterprise in the past few months and listed below, RNA injections, new drug compounds, injectable patches, and synthetic tissue are being developed and tested as treatments.

Source – University of Alabama in Birmingham

Gao L, Gregorich ZR, Zhu W, Mattapally S, Oduk Y, Lou X, Kannappan R, Borovjagin AV, Walcott GP, Pollard AE, Fast VG, Hu X, Lloyd SG, Ge Y, Zhang J. (2017) Large Cardiac-Muscle Patches Engineered from Human Induced-Pluripotent Stem-Cell-Derived Cardiac Cells Improve Recovery from Myocardial Infarction in Swine. Circulation [Epub ahead of print]. [abstract]

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