-Rodent hearts can regenerate myocardium lost to apical resection or myocardial infarction for up to 7 days after birth, but whether a similar window for myocardial regeneration also exists in large mammals is unknown. -Acute myocardial infarction (AMI) was surgically induced in neonatal pigs on postnatal days 1, 2, 3, 7, and 14 (i.e., the P1, P2, P3, P7, and P14 groups, respectively). Cardiac systolic function was evaluated before AMI and at 30 days post AMI via transthoracic echocardiography. Cardiomyocyte cell cycle activity was assessed via immunostaining for proliferation and mitosis markers, infarct size was evaluated histologically, and telomerase activity was measured by quantitative PCR. -Systolic function at day 30 post- AMI was largely restored in P1 animals and partially restored in P2 animals, but significantly impaired when AMI was induced on postnatal day 3 or later. Hearts of P1 animals showed little evidence of scar formation or wall thinning on day 30 after AMI, with increased measures of cell-cycle activity seen six days after AMI (i.e. postnatal day 7) compared to postnatal day 7 in noninfarcted hearts. -The neonatal porcine heart is capable of regeneration following AMI during the first 2 days of life. This phenomenon is associated with induction of cardiomyocyte proliferation, and is lost when cardiomyocytes exit cell cycle shortly after birth.
The regenerative capacity of an adult cardiac tissue is insufficient to repair the massive loss of heart tissue, particularly cardiomyocytes (CMs), following ischemia or other catastrophic myocardial injuries. The delivery methods of therapeutics agents, such as small molecules, growth factors, exosomes, cells, and engineered tissues have significantly advanced in medical science. Furthermore, with the controlled release characteristics, nanoparticle (NP) systems carrying drugs are promising in enhancing the cardioprotective potential of drugs in patients with cardiac ischemic events. NPs can provide sustained exposure precisely to the infarcted heart via direct intramyocardial injection or intravenous injection with active targets. In this review, we present the recent advances and challenges of different types of NPs loaded with agents for the repair of myocardial infarcted heart tissue.
Background-We have shown that genetic overexpression of cell cycle proteins can increase the proliferation of transplanted cardiomyocytes derived from human induced-pluripotent stem cells (hiPSC-CMs) in animal models of myocardial infarction (MI). Here, we introduce a new, nongenetic approach to promote hiPSC-CM cell cycle activity and proliferation in transplanted human cardiomyocyte patches (hCMPs).Methods-Mice were randomly distributed into 5 experimental groups (n = 10 per group). One group underwent Sham surgery, and the other 4 groups underwent MI induction surgery followed by treatment with hCMPs composed of hiPSC-CMs and nanoparticles that contained CHIR99021 and FGF1 (the NP CF -hCMP group), with hCMPs composed of hiPSC-CMs and empty nanoparticles (the NP E -hCMP group); with patches containing the CHIR99021/FGF-loaded nanoparticles but lacking hiPSC-CMs (the NP CF -Patch group), or patches lacking both the nanoparticles and cells (the E-Patch group). Cell cycle activity was evaluated via Ki67 and Aurora B expression, bromodeoxyuridine incorporation, and phosphorylated histone 3 levels (immunofluorescence); engraftment via human cardiac troponin T or human nuclear antigen expression (immunofluorescence) and bioluminescence imaging; cardiac function via echocardiography; infarct size and wall thickness via histology; angiogenesis via isolectin B4 expression (immunofluorescence); and apoptosis via TUNEL and caspace 3 expression (immunofluorescence).
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