A few weeks ago, we reported on the creation of microengineered particle-based cardiac tissue function by functionalizing PLGA microparticles with cardiac cell-extracted growth factors. This week, a new manuscript took this concept even further: The lab of Dr. Muhammad Yousaf at the Department of Chemistry and Biology at York University in Toronto described the generation of a functional, entirely cell-based cardiac tissue based on rapid inter-cell click ligation of multiple cell types.
No external scaffold was used. Instead, the authors relied on cardiomyocytes, cardiac fibroblasts and human umbilical vein endothelial cells (HUVECs) to construct the cardiac tissue.
Oxyamine and ketone-functionalized liposomes were used to deliver the two compounds to cells. When cells bearing the two compounds come into contact with each other, they “click” together via oxime ligation to form spheroids and then tissues.
The authors observed that cells not treated with liposomes formed 2D monolayers rather than 3D structures.
Cardiac-specific markers (Cx43, cTnT) were detected via fluorescent imaging. They were not present on 2D cultures.
Over time, the 3D cultures secreted collagen and elastin, while cardiac function was measured by the propagation of calcium through the cell cytoplasm via a calcium-binding fluorescent dye.
Additionally, the authors studied the effect of two chronotropic drugs – isoprenaline and doxorubicin- on beating rate. They observed that all tissues had an increase in beating rate in response to an increase of concentration of isoprenaline, with a decrease after doxorubicin treatment.
This remarkable system can be considered as a promising drug screening model, or a model disease platform. Further work can show the applicability of the system to other disease models – perhaps using different cell types.
The manuscript can be accessed from Scientific Reports.