Cardiac Cell Culture Model As a Left Ventricle Mimic for Cardiac Tissue Generation

Abstract

A major challenge in cardiac tissue engineering is the delivery of hemodynamic mechanical cues that play a critical role in the early development and maturation of cardiomyocytes. Generation of functional cardiac tissue capable of replacing or augmenting cardiac function therefore requires physiologically relevant environments that can deliver complex mechanical cues for cardiomyocyte functional maturation. The goal of this work is the development and validation of a cardiac cell culture model (CCCM) microenvironment that accurately mimics pressure-volume changes seen in the left ventricle and to use this system to achieve cardiac cell maturation under conditions where mechanical loads such as pressure and stretch are gradually increased from the unloaded state to conditions seen in vivo. The CCCM platform, consisting of a cell culture chamber integrated within a flow loop was created to accomplish culture of 10 day chick embryonic ventricular cardiomyocytes subject to 4 days of stimulation (10 mm Hg, ~13% stretch at a frequency of 2 Hz). Results clearly show that CCCM conditioned cardiomyocytes accelerate cardiomyocyte structural and functional maturation in comparison to static unloaded controls as evidenced by increased proliferation, alignment of actin cytoskeleton, bundle-like sarcomeric α-actinin expression, higher pacing beat rate at lower threshold voltages and increased shortening. These results confirm the CCCM microenvironment can accelerate immature cardiac cell structural and functional maturation for potential cardiac regenerative applications.

Bioreactor for modulation of cardiac microtissue phenotype by combined static stretch and electrical stimulation

“…This finding shows the importance of anisotropy in engineered myocardium and the importance of cardiomyocyte elongation with tension for proper maturation. Optimizing and enhancing mechanical stimulation platforms is an area of active research as evidenced by recent reports of novel bioreactors capable of mechanical stimulation [38, 39]. …”

Heart-on-a-chip based on stem cell biology

“…In cells cultured in static controls, random orientation of F-actin was observed in comparison to aligned F-actin in cells cultured in µCCCM. This microdevice allowed experiments to be performed for evaluating the effects of drugs in different operating conditions to mimic different cardiac dysfunctions.Similar cardiac cell culture model (CCCM) was presented by Nguyen et al(Nguyen et al, 2013). The working cycle of CCCM platform simulated the working cycle of left ventricle.…”

A non-invasive image based system for early diagnosis of prostate cancer.

“…• Testing the proposed mathematical models and learning techniques in other clinical studies, such as detection of lung cancer , early detection of acute renal rejection [113,, and cardiac MRI [111,119,[231][232][233][234][235][236][237][238][239][240][241][242][243][244][245] APPENDIX I…”