For MI, a new patch

DURHAM, N.C.—To date, the only definitive treatment for heart failure is an organ transplant, a solution that is limited by the availability of donor organs and the potential for the patient’s body to reject the new heart. However, findings of a study published in STEM CELLS Translational Medicine demonstrate the promise in regenerating cardiac tissue using engineered patches made up of a mixture of fibrin and mesenchymal stem cells (MSCs) derived from human umbilical cord blood.

Previous studies show the potential of MSCs to repair damage left by a heart attack, but in these instances, the cells were delivered through injections or intravenously. “While feasible and safe, the treatments exhibited only modest benefits,” said Antoni Bayes-Genis, M.D., Ph.D., member of the ICREC (Heart Failure and Cardiac Regeneration) Research Program, Germans Trias i Pujol Health Science Research Institute (IGTP) and professor at Universitat Auto`noma de Barcelona. Dr. Bayes-Genis is a lead investigator on this study.

“The survival rate of the implanted stem cells was generally low and about 90 percent of them either died or migrated away from the implantation site, generally to the liver,” added the study’s first author, Santiago Roura, Ph.D., also a member of the ICREC Research Program and IGTP. “These limited effects are probably due to the adverse mechanical stress and hypoxic conditions present in the myocardium after the heart attack.”

Could finding a better way to deliver the MSCs to the injured site yield more efficient results? Researchers think it’s a possibility. Scaffolds (or patches) in which the cells are combined with biological and synthetic materials that can also be supplemented with growth/differentiation factors to generate bioimplants have emerged as a promising candidate. However, none of the current materials being tested for the patches, whether synthetic or natural, have demonstrated optimal properties for cardiac tissue repair.

That led Dr. Bayes-Genis and his colleagues to investigate how a fibrin patch filled with human umbilical cord blood-derived MSCs might work. Fibrin is already widely used in medical applications due to its ability to act as a bio-compatible glue, holding cells in place and stimulating angiogenesis. In turn, they surmised that it might offer a nurturing environment for the MSCs’ proliferation while also keeping them at the site of the injury where they were needed for repairing the heart tissue.

The team mixed MSCs and fibrin to form the patches and then administered them in a group of mice that had undergone heart attacks. Three weeks later, they compared the animals’ recovery to a control group of mice treated with fibrin alone (no stem cells) and another control group that received no treatment at all. The results showed that the patches adhered well to the hearts and the MSCs demonstrated early proliferation and differentiation. The patch cells also participated in the formation of new, functional blood vessels that connected the patch to both the heart tissue directly beneath it and the mouse’s circulatory system as well.

“As a result, the heart function in this group of mice was better than that of the animals in either of the other control groups,” Dr. Bayes-Genis said. “Thus, this study provides promising findings for the use of umbilical cord-blood MSCs and fibrin patches in cardiac repair.”

The study abstract provides details. Human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) were modified to coexpress luciferase and fluorescent protein reporters, mixed with fibrin, and applied as an adhesive, viable construct (fibrin-cell patch) over the infarcted myocardium in mice (MI-UCBMSC group), the researchers explain in the study abstract. The patch adhered well to the heart. Noninvasive bioluminescence imaging demonstrated early proliferation and differentiation of UCBMSCs within the construct in the postinfarct mice in the MI-UCBMSC group. The implanted cells also participated in the formation of new, functional microvasculature that connected the fibrin-cell patch to both the subjacent myocardial tissue and the host circulatory system. As revealed by echocardiography, the left ventricular ejection fraction and fractional shortening at sacrifice were improved in MI-UCBMSC mice and were markedly reduced in mice treated with fibrin alone and untreated postinfarction controls. In conclusion, a 3D engineered fibrin patch composed of UCBMSCs attenuated infarct-derived cardiac dysfunction when transplanted locally over a myocardial wound.

The full article, “Post-infarction functional recovery driven by a three dimensional engineered fibrin patch comprised of human umbilical cord blood-derived mesenchymal stem cells,” can be accessed at http://www.stemcellstm.com.