Mammal cardiomyocytes lose their ability of regeneration shortly after birth. Reduced cardiomyocytes number caused by myocardial damage is unable to reverse in current clinical therapies. Therefore, it is important and urgent to find new approaches to stimulate cardiomyocytes regeneration. Here we design a recombinant protein IGF1-24 and show that it triggers cardiomyocytes proliferation in rat. 7 days after tail intravenous injection of IGF1-24 ， 6-7-weeks-old healthy rats showed marked improvements in cardiomyocytes proliferation. Next, we injured rats cardiac with isoproterenol and treated them with IGF1-24 injection. We found that it efficiently induced cell proliferation with significant improvements in heart histology. These results show that the recombinant IGF1-24 stimulates cardiomyocytes proliferation and can be used to achieve cardiac repair through stimulating endogenous cardiomyocyte proliferation in rats. The IGF 1-24 could be a prospective medicine to heart repair because it has high efficiency in triggering cell proliferation and it can be easily applied to heart by intravenous injection

Background: Sepsis is a systemic inflammatory response to a local severe infection that can lead to multiple organ failure and ultimately death. Studies have shown that 40%-50% of septic patients have diverse myocardial injuries, with mortality ranging from 70% to 90% in contrast to 20% in septic patients without myocardial injury. Therefore, uncovering the mechanism of myocardial injury induced by sepsis and finding a treatment for the corresponding target are immensely important.Methods: We employed cecal ligation and puncture (CLP) for inducing sepsis in mice, and detect the situation of myocardial injury and cardiac function through serological markers and echocardiography. The cardiomyocytes apoptosis and the ultrastructural of heart tissue detected by TUNEL and transmission electron microscope (TEM) respectively. The Fura-2 AM was used to monitored Ca2+ uptake and efflux of mitochondria. FQ-PCR and Western blot detected the expression of mitochondria Ca2+ distribution regulators and PINK1. JC-1 was used to detected the mitochondrial membrane potential (Δψm) of cardiomyocytes. Results: We found that the expression of PINK1 decreased in mouse hearts during sepsis, which caused cardiomyocyte mitochondrial calcium efflux disorder, mitochondrial calcium overload and cardiomyocyte injury. In contrast, we found that exosomes isolated from huMSCs (huMSCs-exo) carried Pink1 mRNA that could be transferred to recipient cardiomyocytes, increasing PINK1 expression. Then, the reduction in cardiomyocyte mitochondrial calcium efflux was reversed, and cardiomyocytes recovered from their injury. Furthermore, we confirmed the effect of the PINK1-PKA-NCLX axis on mitochondrial calcium homeostasis in cardiomyocytes during sepsis.Conclusion: The PINK1-PKA-NCLX axis play an important role in cardiomyocytes mitochondrial calcium efflux, therefore PINK1 could be a therapeutic target to protect cardiomyocyte mitochondria, and the application of huMSCs-exo is a promising strategy against heart dysfunction induced by sepsis.