The combination of agrin, BRP44, and insulin (ABI) promote human CM proliferation

Human cardiomyocytes (CMs) differ from those of rodents in many aspects, and methods that effectively improve cardiac performance in rodents have been unsuccessful in humans, indicating a translational gap between humans and rodents in cardiac regeneration. The CM proliferation transition between the neonatal and adult stages is well-established in humans and rodents. The aim of the study is to analyze human atrial CM proliferation-transition for narrowing down the translational gap between humans and rodents in cardiac regeneration.At first we extracted decellularized samples (DS) from human atrial specimens collected during routine congenital cardiac surgery from children diagnosed with ventricular septal defect (VSD). The DS was next used for cell culture and proteomic analyses. The proteins (such as Agrin, BRP44, and insulin) identified in the proteomic analysis were further verified by testing their ability to promote CM proliferation. The results showed that the combination of agrin, BRP44, and insulin (ABI) enhanced the effect of agrin.To further confirmed the role of ABI on human CM proliferation, we performed RNA-seq on the ABI-treated HiPSC-CMs. The results showed that ABI induced abundant enrichment of cell-cycle associated genes, which highlighting the synergy of hormones and anti-oxidation/metabolism in human CM proliferation.