Hopkins researchers, working with a team from South Korea, have created a chip that works as a matrix on which cardiac tissue can be grown. Heart cells grown on the chip, which mimics the extracellular matrix (ECM), look more like actual cardiac tissue found in the body than do cells grown on ordinary petri dishes.
Deok-Ho Kim, a researcher at Hopkins's Department of Biomedical Engineering and lead author of the study, and his team noted strong evidence suggesting that macroscopic cardiac tissue is highly influenced by the nanoscale topographic features of the ECM. The ECM affects both the structure and the function of heart cells that grow on it.
The three major cell types of cardiac tissue are cardiomyoctes that form the heart's contractile muscle, vascular endothelial cells that make up the inner lining of cardiac blood vessels, and smooth muscle cells of the walls of the blood vessels in the heart. Together, these cardiac tissues are known as myocardium.
The different cells are organized in a highly specific manner in the well-defined and intricate structures of the ECM.
Like all other living cells and tissues, cardiac tissue is very sensitive to the topographical features of the surrounding ECM. However, the miniscule interactions prevented past researchers from fully understanding cardiac functions at the subcellular and nanoscale levels.
Previous studies have only demonstrated the importance of nanoscopic cues in cell signaling, adhesion, growth and differentiation. Attempts to artificially manipulate cardiac function have failed, as the cells lose their original organization and scatter randomly when cultured via common in vitro methods on smooth-surfaced petri dishes.
Kim speculates that the results were most likely due to failure to consider nanoscopic cues of the ECM, which may underlie the complex controls of cardiac tissue functions.
The research team used several standard protocol techniques to perform ultrastructural analysis of ex vivo rat myocardium.
Results show that in addition to identifiable anisotropic groups of elongated and well-aligned cells in the cardiac tissue next to an ECM fiber layer, the cell orientations also strongly parallel the direction of alignment of matrix fibers directly below.
This discovery implies that the ECM organization may provide nanotopographic cues to guide myocardial alignment during cardiovascular development.
The biocompatible chips were made to precisely control nanoscale topography. As expected, the substrata caused the cells to grow in the direction of the underlying nanoridges on the chip. The relationship between adjacent cells grown on the chips also resembled that between adjacent cells in natural heart tissue.
Furthermore, numerous cell properties were sensitive to the exact nanotopographic pattern, even when differences in cell geometry and function were taken into consideration.
This study demonstrated the importance of investigating further the nanoscale properties of cardiac tissue in order to better understand natural conditions controlling heart function and structure. This work also opens up the possibility of developping engineered cardiac tissue for future therapeutic products.
In the future, the team wants to consider the possibility of expanding the currently two-dimensional chip to three dimensions, to even better mimic conditions in the body.
Their findings were published in the Proceedings of the National Academy of Sciences.
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