Human Induced Pluripotent Stem Cell–Derived Cardiomyocyte Patch in Rats With Heart Failure

Surgical treatment for heart failure: cell-based therapy with engineered tissue

“…Lancaster et al [35] have developed a TE cardiac patch composed of a bioabsorbable scaffold embedded with human neonatal fibroblasts and PSC-CMs that is implanted on the epicardial surface of the heart to treat CHF. The fibroblasts proliferate and synthesize glycosaminoglycans, collagen, elastin, fibronectin and laminin while providing a secretome of growth factors and cytokines.…”

“…[47] PSC-CMs Allo Bioabsorbable polymer Pre-clinical Lancaster et al . [35] PSC-CMs Allo Cell sheets Clinical Cyranoski/Sawa [27] TE: tissue engineering; Allo: allogeneic; Auto: autologus; hdECM: decellularized extracellular matrix; ES: embryonic stem; EHT: engineered heart tissue; PSC-CMs: human induced pluripotent stem cell-derived cardiomyocytes; PCLA:sponge polymer of epsilon-caprolactone-co-L-lactide reinforced with knitted poly-L-lactide fabric approaches, a secretome of soluble factors such as growth factors, exosomes, and miRNAs are thought to be responsible for the beneficial effects [48][49][50] . The specific paracrine stimulation may vary by implanted cell type and may be modulated by the cell culture environment, delivery platform, and other relevant variables.…”

“…The finding of increased incidence of ventricular tachyarrhythmia has also been reported with human embryonic stem cell-derived cardiomyocyte injections into non-human primates and swine hearts [51,52] . Interestingly in preclinical studies with PSC-CMs TE scaffolds implanted on the epicardium, the animals remain in normal sinus rhythm without any arrhythmias [20,35] .…”

Highly purified extracellular vesicles from human cardiomyocytes demonstrate preferential uptake by human endothelial cells

“…3d). 52 We then quantified an enrichment factor between peak EV rich fractions (fractions 8 and 9) and compared this to the mean soluble protein rich fractions (fractions [15][16][17][18][19][20][21][22][23][24]. We identified that the endosomal protein markers Lamp1 and CD63 were substantially more highly enriched in the EV-containing fractions; while the cytoplasmic proteins Alix and HSP70 showed some enrichment in LAC-CM-EVs, but to a lesser extent than the endosomal protein markers (Fig.…”

“…14 More recently, instead of delivering cells systemically or by intramyocardial injection, iPSC-derived cardiomyocytes, and other stem cells have been localized to damaged regions within biomaterial patches. [15][16][17] Nevertheless, poor integration between the biomaterial and pre-existing cardiac tissue has raised safety concerns and limited the translatability of these approaches.…”