Study of Stem Cells Influence on Cardiac Cells Cultured with a Cyanide-P-Trifluoromethoxyphenylhydrazone in Organ-on-a-Chip System

Abstract

Regenerative medicine and stem cells could prove to be an effective solution to the problem of treating heart failure caused by ischemic heart disease. However, further studies on the understanding of the processes which occur during the regeneration of damaged tissue are needed. Microfluidic systems, which provide conditions similar to in vivo, could be useful tools for the development of new therapies using stem cells. We investigated how mesenchymal stem cells (MSCs) affect the metabolic activity of cardiac cells (rat cardiomyoblasts and human cardiomyocytes) incubated with a potent uncoupler of mitochondrial oxidative phosphorylation under microfluidic conditions. A cyanide p-trifluoromethoxyphenylhydrazone (FCCP) was used to mimic disfunctions of mitochondria of cardiac cells. The study was performed in a microfluidic system integrated with nanofiber mats made of poly-l-lactid acid (PLLA) or polyurethane (PU). The microsystem geometry allows four different cell cultures to be conducted under different conditions (which we called: normal, abnormal—as both a mono- and co-culture). Metabolic activity of the cells, based on the bioluminescence assay, was assessed in the culture’s performed in the microsystem. It was proved that stem cells increased metabolic activity of cardiac cells maintained with FCCP.

Integrated biosensors for monitoring microphysiological systems

“…In another work, on-chip AlamarBlue assays were conducted to evaluate the metabolic activity of cardiac and stem cells. 79 In this paper, a non-toxic and cell-permeable dye (resazurin) was used to detect oxidation levels during cell respiration. Using microfluidics, these biosensors have the following advantages: low maintenance, higher analysis speed, low cost, enhanced process performance, and reduced reagent consumption.…”

Review of Cyanotoxicity Studies Based on Cell Cultures

“…The use of cell cultures in toxicological studies will remain the main approach due to its speed, relatively low cost, reproducibility, precision with respect to the studied intracellular components, and ethical acceptability. The use of cell cocultures [ 116 – 118 ] and in vitro formed organ-like structures such as artificial neuronal network [ 119 ], cardiomyocyte spheroids with contractile activity [ 120 ], and organ-on-a-chip systems [ 121 ], which are functionally closer to the human body [11], will increase in the future.…”