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Future of Mice Research

Myocardial Infarction Repair

A major focus of cardiovascular research is centered on trying to repair the heart after a myocardial infarction, MI, more commonly referred to as a heart attack. The heart is damaged by a lack of blood flow to tissue which can lead to cell death. This injury results in scars formed by fibroblasts because heart muscle cells are unable to proliferate and fill the area damaged by the MI. A promising area of research that is growing is stem cell therapies in which stem cells are either differentiated into a patch of cells or injected straight into the damaged tissue. A schematic for how that might be done is pictured below in a figure adapted from Lalit et al., 2014. Mice and primates are both being used to model this type of research. Mice are more effective in showing how these therapies might be beneficial and are easier to manipulate for these experiments. Unfortunately, this research still has some major hurdles to overcome. There is concern that the use of these stem cells can lead to malignancies as a result of how they are transformed into different cell types like through viral vectors that may cause random mutations. Another concern is that after transplantation, the cells used could have runaway proliferation. This is not as much of a concern with cardiac myocytes due to the terminal stage of differentiation and are not proliferative. Concerning the nature of the cell type, there is potential for arrhythmias to occur due to immature electrophysiological development of these cells. There is research aimed at maturing iPSC-derived cardiomyocytes prior to transplantation to improve this weakness. Lastly, it is still relatively unknown how transplantation of stem cell derived cardiac myocytes are mechanistically contributing to improvement of the heart. This is a pressing area that is being explored and should eventually reveal why there is a lower survival rate of transplanted cells and how to fix this issue.

Figure 2.

Lalit, P. A., Hei, D. J., Raval, A. N., & Kamp, T. J. (2014). Induced pluripotent stem cells for post-myocardial infarction repair: remarkable opportunities and challenges. Circulation research114(8), 1328–1345. https://doi.org/10.1161/CIRCRESAHA.114.300556
Sun, H., Pratt, R. E., Dzau, V. J., & Hodgkinson, C. P. (2023). Neonatal and adult cardiac fibroblasts exhibit inherent differences in cardiac regenerative capacity. The Journal of biological chemistry299(5), 104694. https://doi.org/10.1016/j.jbc.2023.104694
Jiang, X., Yang, Z. & Dong, M. Cardiac repair in a murine model of myocardial infarction with human induced pluripotent stem cell-derived cardiomyocytes. Stem Cell Res Ther 11, 297 (2020). https://doi.org/10.1186/s13287-020-01811-7