GSE204881
Cardiovascular progenitors regenerate infarcted swine hearts
Stem cell-derived products could replace damaged heart muscle in regenerative cardiology. Here, human embryonic stem cells (hESCs) were differentiated on laminin 521+221 to cardiovascular progenitors (CVPs). The CVPs were transplanted into the infarcted region of 10 pigs and maintained for 4- and 12- weeks. Immunohistology analyses revealed in vivo engraftment and maturation of the CVPs into cardiomyocytes (CMs). Furthermore, heart function was analyzed by magnetic resonance imaging (MRI). We observed significant improvement in the left ventricular ejection fraction (DLVEF: 21.9 ± 1.6 %, at 12-weeks), ventricular wall thickness and wall motion, as well as a reduction in infarction size after CVP transplantation as compared to control pigs (p-value < 0.05). There are temporary episodes of ventricular tachyarrhythmia (VT) in four pigs and one pig had persistent VT. On the other hand, the remaining 5 pigs remained in normal sinus rhythm. Importantly, all pigs survived without any VT-related death, suggesting the potential for developing CVPs towards applications in regenerative cardiology. Overall design: Human embryonic stem cells were cultured in wells coated with LN-521+LN-221 using nutristem medium. RNA is extracted when cells reached confluence. Bulk RNA-seq and single cell RNA-seq are performed on Day 0, 4, 9, 11, 20 of differentiation.