Magnetic Resonance Imaging of Cardiac Strain Pattern Following Transplantation of Human Tissue Engineered Heart Muscles

Abstract

Background The use of tissue engineering approaches in combination with exogenously produced cardiomyocytes offers the potential to restore contractile function after myocardial injury. However, current techniques assessing changes in global cardiac performance following such treatments are plagued by relatively low detection ability. As the treatment is locally performed, this detection could be improved by myocardial strain imaging that measures regional contractility. Methods and Results Tissue engineered heart muscles (EHMs) were generated by casting human embryonic stem cell-derived cardiomyocytes with collagen in preformed molds. EHMs were transplanted (n=12) to cover infarct and border zones of recipient rat hearts one month after ischemia reperfusion injury. A control group (n=10) received only sham placement of sutures without EHMs. To assess the efficacy of EHMs, MRI and ultrasound-based strain imaging were performed prior to and four weeks after transplantation. In addition to strain imaging, global cardiac performance was estimated from cardiac MRI. Although no significant differences were found with global changes in left ventricular ejection fraction (EF) (Control −9.6±1.3% vs. EHM −6.2±1.9%, P=0.17), regional myocardial strain from tagged MRI was able to detect preserved systolic function in EHM-treated animals compared to control (Control 4.4±1.0% vs. EHM 1.0±0.6%, P=0.04). However, ultrasound-based strain failed to detect any significant change (Control 2.1±3.0% vs. EHM 6.3±2.9%, P=0.46). Conclusions This study highlights the feasibility of using cardiac strain from tagged MRI to assess functional changes in rat models due to localized regenerative therapies, which may not be detected by conventional measures of global systolic performance.

Photoacoustic Imaging of Embryonic Stem Cell‐Derived Cardiomyocytes in Living Hearts with Ultrasensitive Semiconducting Polymer Nanoparticles

“…Human embryonic stem cell line WA07 (H7) and cardiomyocyte differentiation using small molecules were based on protocols described in previous studies [25] . Before labeling, hESC-CMs were dissociated and re-seeded into a new Matrigel-coated plate to form a single monolayer of cells.…”

ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure

“…With the advent of human pluripotent stem cells (hPSC), including human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC), the availability of large-scale production in bioreactors and differentiation/purification protocols, sufficient quantities of essentially pure human cardiomyocytes can be produced according to GMP requirements and applied in the engineering of heart muscle. 19 Human EHM rings and patches [19][20][21] as well as human engineered heart tissue strips 22 from human embryonic (hESC)-and hiPSC-derived cardiomyocytes could be implanted and used to partially repair large muscle defects in rat and guinea-pig hearts. These studies collectively demonstrated long-term cardiomyocyte retention (>200 days), maturation, graft vascularization, and a variable degree of proliferation; further electrical coupling to the host myocardium was observed in some, but not all investigated guinea-pigs, 22 in line with earlier studies demonstrating the isolation of human engineered muscle xenograft grafts by scar formation in athymic rats.…”

Imaging the Cardiac Extracellular Matrix

“…T1 mapping sequences are not standardized, making measurements difficult to reproduce or interpret across institutions [52]. A final set of techniques, tagging and feature tracking MRI, are reproducible and quantitative, but only indirectly measure collagen or other ECM biology [55]. Tagging and feature tracking measure the mechanical deformation (strain) of the myocardium, which is affected by the collagen structure [52].…”