Review of Heart Regeneration by using induced Pluripotent Stem Cells and extracellular matrix protein, Agrin, in Mice and Primate hearts. Buntongyi Nit1, Don Eliseo Lucero-Prisno III2, Xu Lin3, Hang Cao4, Yusuff Adebayo Adebisi5 1University of Puthisastra, 2Xi'an Jiaotong-Liverpool University (XJTLU), 3Soochow University, 4Central South University, 5University of Ibadan, Nigeria Introduction, Objective: Heart failure is the leading cause of death worldwide. In mammals, post-mitotic adult cardiomyocytes (CMs) have limited capacity to replenish damaged tissue. Lately, medical treatment for patients with severe heart failure still has not much benefit. Surgeries, including cardiac transplantation and the implantation of ventricular assist devices, are available for only a limited number of patients. Since the number of patients is high and therapy supplies are bounded, therefore, the significant value of heart regeneration researches is needed to discover. Human induced Pluripotent Stem Cells (iPSCs), like human embryonic stem (ES) cells, are a promising cell source for cardiac reconstruction because of their unlimited self-renewal and ability to differentiate into CMs. The peer-reviewed of this paper is to introduce induced Pluripotent Stem Cells (iPSCs) technology along with the extracellular matrix protein, Agrin, for cardiac application in the near future. Results: iPSCs have a great potential in heart diseases regarding the studies of iPSCs toward clinical applications including cardiac arrhythmias, cardiomyopathies and myocarditis. According to the data, allogeneic iPSC-CM transplantation is adequate to regenerate the infarcted non-human primate heart. However, post-transplant arrhythmias are still considered. Providentially, Agrin, is a large extracellular heparan sulfate proteoglycan which involve in the formation of the neuromuscular junction. Based on the studies, Agrin is the additional source that promotes CM proliferation in vitro. Taken together, administration of either human or rat Agrin dose-dependently enhanced human iPSC-CM cell cycle activity. Figure 1. WHO, the top 10 causes of death Worldwide Figure 2. Current applications of patient-specific induced pluripotent (iPSC-CM) technology. stem cell–derived cardiomyocyte Figure 3. A model for Agrin-DGC-Yap signaling axis in CM maturation and cardiac regeneration. Figure 4. Macroscopic and microscopic analysis of iPSC-CM recipients. Figure 5. Agrin induces cardiac Regeneration in adult mice. Methods: Studies are identified by searching several articles from Nature, Pubmed and Hinari relating to heart regeneration using iPSCs technology and Agrin in mice and primate heart between 2010-2017. Figure 6. Additional electrical analysis of hearts transplanted with iPSC-CMs. Conclusions: In vitro studies revealed the great prospect of iPSC therapy on cardiac diseases and expected to make them a powerful tool for providing new therapeutic insights in the era of precision medicine. Before extending to this level, nevertheless, there are several issues such as arrhythmias, should be addressed. More than that, in vivo study is needed to investigate in the next stage. References: Bassat, E., Mutlak, Y. E., Genzelinakh, A., Shadrin, I. Y., Baruch-Umansky, K., Yifa, O., ... & Udi, Y. (2017). The extracellular matrix protein Agrin promotes heart regeneration in mice. Nature. Yoshida, Yoshinori, and Shinya Yamanaka. "Induced Pluripotent Stem Cells 10 Years Later." Circulation Research 120.12 (2017): 1958-1968. Shiba, Y., Gomibuchi, T., Seto, T., Wada, Y., Ichimura, H., Tanaka, Y., ... & Ido, D. (2016). Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts. Nature. Ioannis Karakikes, Mohamed Ameen, Vittavat Termglinchan, Joseph C. Wu. (2015). Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Insights Into Molecular, Cellular, and Functional Phenotypes. Circulation Research 117:80-88 Corresponding details: Buntongyi Nit, MS6; Tel: +855 (0) 78331117 – btongyinit@gmail.com -