Scientists Develop a New Way to Turn Stem Cells into Heart Cells

Researchers from the Moscow Institute of Physics and Technology (MIPT), the M.F. Vladimirsky Moscow Regional Research Clinical Institute, and the E.N. Meshalkin National Medical Research Center have taken an important step toward advancing regenerative medicine. The scientists developed an accessible and effective method for producing heart muscle cells (cardiomyocytes) from mesenchymal stem cells derived from bone marrow. The parallel differentiation technology makes it possible to create personalized tissues without expensive genetic engineering or complex chemical cocktails. The findings were published in the scientific journal Biomedicines.

Regenerative therapy makes it possible to replace damaged areas of organs and tissues with healthy cells, Nauchnaya Rossiya reports. Traditionally, scientists use induced pluripotent stem cells (iPSCs) to model cardiac tissue. These cells are obtained through a complex and costly process of “reprogramming” mature (somatic) cells from the body, such as skin cells (fibroblasts) or blood cells.

Russian specialists have proposed a more accessible alternative: the use of mesenchymal stem cells, which normally develop into bone, cartilage, or fat tissue. The researchers isolated stem cells from small samples of red bone marrow weighing just 1–2 grams, collected from patients during open-heart surgery. The isolated cells were placed in a special culture medium containing cardiomyocytes grown using a standard protocol. As a result of paracrine signaling—the influence of signaling molecules released by mature myocardial cells—the bone marrow stem cells synchronized their activity and began transforming into cardiomyocyte-like cells. They successfully acquired key structural and functional characteristics of cardiac tissue, including electrical activity, calcium oscillations, and transverse striation.

One of the study’s authors, Veronika Litvinenko, a research engineer at the Laboratory of Experimental and Cellular Medicine at MIPT’s Institute of Future Biophysics, explained to Nauchnaya Rossiya the advantages of the new technology and its main potential application.

“Cell therapy is an extremely relevant field because stem cells are versatile, proliferate very well, possess immunomodulatory properties, and are multipotent. Their use is highly promising in the treatment of vascular disorders. But we face a serious obstacle: because of individual parameters and clinical characteristics, this type of therapy varies greatly from patient to patient, creating difficulties in cell differentiation. Unfortunately, existing protocols do not provide a universal solution. Our work differs in that, by modeling the microenvironment and adding a special paracrine medium, we modify stem cells and obtain cardiomyocyte-like cells from them. <…> The cells we have obtained could potentially be used to treat, for example, fibrosis that develops after myocardial infarction. During a heart attack, part of the heart loses its blood supply, contractile cells die, and connective-tissue cells called fibroblasts take their place, forming scars. The resulting fibrotic tissue does not contract or conduct electrical excitation waves, which can lead to heart rhythm problems, arrhythmias, and fibrillation. To address this problem, we propose placing the developed cells at the site of fibrosis and converting them into cardiomyocytes that will contract, allowing the heart to function as if it were new.”

The researchers confirmed that the resulting cells corresponded to cardiac tissue using a comprehensive set of advanced methods, including immunohistochemical staining, optical mapping, and the patch-clamp technique. The proposed protocol also eliminates the problem of immune rejection because the new cells are created using the patient’s own biological material, the researcher explained.

It will take considerable time before the method can be introduced into healthcare. At the current stage, the method has an efficiency of up to 15%—meaning that this proportion of stem cells in laboratory culture successfully transforms into cardiac cells. However, the MIPT research team is actively working to increase this rate and shorten the differentiation process. At the same time, researchers are developing optimal methods for delivering the cells directly to the affected area of the heart. The biophysicists’ immediate plans include conducting full-scale tests in animal models, which could eventually pave the way for human clinical trials and the development of personalized models of heart disease.