scholarly journals Microenvironment stiffness requires decellularized cardiac extracellular matrix to promote heart regeneration in the neonatal mouse heart

2020 ◽  
Vol 113 ◽  
pp. 380-392 ◽  
Author(s):  
Xinming Wang ◽  
Subhadip Senapati ◽  
Akinola Akinbote ◽  
Bhargavee Gnanasambandam ◽  
Paul S.-H. Park ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Neonatal Mouse ◽  
Mouse Heart ◽  
Heart Regeneration

Abstract 303: Decreasing Microenvironment Stiffness Improves Exogenous Extracellular Matrix Induced Heart Regeneration in Neonatal Mouse

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Xinming Wang ◽  
Samuel Senyo
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Matrix ◽  
Ejection Fraction ◽  
Heart Function ◽  
Neonatal Mouse ◽  
Mouse Heart ◽  
Heart Regeneration ◽  
Cardiomyocyte Proliferation ◽  
Collagen Crosslinks ◽  
Cardiac Ventricle

Introduction: Transplanting cardiac extracellular matrix (ECM) has been demonstrated to influence healing in post-ischemic hearts. We propose that altering mechanical properties can stimulate a regenerative response in ECM-treated hearts. In this study, we investigate the role of mechanical unloading and solubilized ECM to modulate matrix-induced heart regeneration in low-regenerative P5 neonatal mice after acute myocardial infarction and mouse ventricle explants. Methods: P5 neonatal mouse heart stiffness was lowered by inhibiting formation of new collagen crosslinks. Solubilized fetal ECM was injected immediately after myocardial infarction (MI). Heart function and histology were conducted at week 3 post-MI. Cardiac ventricle explants were also used to investigate relevant signaling pathways. Results: We observed that lowering tissue stiffness increased the regenerative influence of fetal ECM treatment on heart function, fibrosis, and cardiomyocyte proliferation. Decrease heart stiffness inhibits fibrosis and better preserves heart function in fetal ECM treated hearts (Figure 1). We further provide evidence that yes-associated protein (Yap) signaling pathway plays a role in ECM-induced cardiomyocyte proliferation possibly through cytoskeleton polymerization.The results suggest that the native microenvironment stiffness, particularly with aging or post-ischemia, affects the therapeutic efficacy of drugs for heart disease. Figure 1 . Fetal ECM treatment P5 mouse hearts showed a higher ejection fraction in comparison with the control hearts at 3-weeks post-MI. Decreasing heart stiffness in P5 mouse heart further promoted increased ejection fraction in fetal ECM treated animals. (n=5, two-way ANOVA test and Tukey’s test, *p<0.05, ****p<0.0001.)

scholarly journals Decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration

2016 ◽  
Vol 2 (11) ◽  
pp. e1600844 ◽  
Author(s):  
William C. W. Chen ◽  
Zhouguang Wang ◽  
Maria Azzurra Missinato ◽  
Dae Woo Park ◽  
Daniel Ward Long ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Adult Mouse ◽  
Contractile Function ◽  
Left Ventricular ◽  
Precursor Cell ◽  
Cell Populations ◽  
Mouse Heart ◽  
Heart Regeneration ◽  
Regenerative Capacity ◽  
Mammalian Heart

Heart attack is a global health problem that leads to significant morbidity, mortality, and health care burden. Adult human hearts have very limited regenerative capability after injury. However, evolutionarily primitive species generally have higher regenerative capacity than mammals. The extracellular matrix (ECM) may contribute to this difference. Mammalian cardiac ECM may not be optimally inductive for cardiac regeneration because of the fibrotic, instead of regenerative, responses in injured adult mammalian hearts. Given the high regenerative capacity of adult zebrafish hearts, we hypothesize that decellularized zebrafish cardiac ECM (zECM) made from normal or healing hearts can induce mammalian heart regeneration. Using zebrafish and mice as representative species of lower vertebrates and mammals, we show that a single administration of zECM, particularly the healing variety, enables cardiac functional recovery and regeneration of adult mouse heart tissues after acute myocardial infarction. zECM-treated groups exhibit proliferation of the remaining cardiomyocytes and multiple cardiac precursor cell populations and reactivation of ErbB2 expression in cardiomyocytes. Furthermore, zECM exhibits pro-proliferative and chemotactic effects on human cardiac precursor cell populations in vitro. These contribute to the structural preservation and correlate with significantly higher cardiac contractile function, notably less left ventricular dilatation, and substantially more elastic myocardium in zECM-treated hearts than control animals treated with saline or decellularized adult mouse cardiac ECM. Inhibition of ErbB2 activity abrogates beneficial effects of zECM administration, indicating the possible involvement of ErbB2 signaling in zECM-mediated regeneration. This study departs from conventional focuses on mammalian ECM and introduces a new approach for cardiac tissue regeneration.

Abstract 148: Neonatal Mouse Heart Regeneration is Dependent on Mononuclear Diploid Cardiomyocytes and Paracrine IGF2 Signaling

2019 ◽  
Vol 125 (Suppl_1) ◽  
Author(s):  
Hua Shen ◽  
Michaela Patterson ◽  
Peiheng Gan ◽  
Henry M Sucov
Keyword(s):  
Neonatal Mouse ◽  
Mouse Heart ◽  
Heart Regeneration

Response to “Comment to the article ‘A systematic analysis of neonatal mouse heart regeneration after apical resection’”

2015 ◽  
Vol 82 ◽  
pp. 184-185 ◽  
Author(s):  
Donald Marion Bryant ◽  
Caitlin Claire O'Meara ◽  
Nhi Ngoc Ho ◽  
Joseph Gannon ◽  
Lei Cai ◽  
...  
Keyword(s):  
Neonatal Mouse ◽  
Mouse Heart ◽  
Heart Regeneration ◽  
Systematic Analysis

scholarly journals A systematic analysis of neonatal mouse heart regeneration after apical resection

2015 ◽  
Vol 79 ◽  
pp. 315-318 ◽  
Author(s):  
Donald Marion Bryant ◽  
Caitlin Claire O'Meara ◽  
Nhi Ngoc Ho ◽  
Joseph Gannon ◽  
Lei Cai ◽  
...  
Keyword(s):  
Neonatal Mouse ◽  
Mouse Heart ◽  
Heart Regeneration ◽  
Systematic Analysis

scholarly journals Author response: Mononuclear diploid cardiomyocytes support neonatal mouse heart regeneration in response to paracrine IGF2 signaling

2020 ◽  
Author(s):  
Hua Shen ◽  
Peiheng Gan ◽  
Kristy Wang ◽  
Ali Darehzereshki ◽  
Kai Wang ◽  
...  
Keyword(s):  
Neonatal Mouse ◽  
Author Response ◽  
Mouse Heart ◽  
Heart Regeneration

scholarly journals Coupled myovascular expansion directs growth and regeneration of the neonatal mouse heart

2021 ◽  
Author(s):  
Paige DeBenedittis ◽  
Anish Karpurapu ◽  
Albert Henry ◽  
Michael C Thomas ◽  
Timothy J McCord ◽  
...  
Keyword(s):  
Cell Types ◽  
Neonatal Mouse ◽  
Border Zone ◽  
Mouse Heart ◽  
Heart Regeneration ◽  
Cardiac Growth ◽  
Spatial Coupling ◽  
Epicardial Cells ◽  
Multiple Cell ◽  
Vegfr2 Signaling

ABSTRACTInnate heart regeneration in zebrafish and neonatal mammals requires multiple cell types, such as epicardial cells, nerves, and macrophages, to enable proliferation of spared cardiomyocytes (CMs). How these cells interact to create growth niches is unclear. Here we profile proliferation kinetics of cardiac endothelial cells (CECs) and CMs in the neonatal mouse heart and find that CM and CEC expansion is spatiotemporally coupled. We show that coupled myovascular expansion during cardiac growth or regeneration is dependent upon VEGF-VEGFR2 signaling, as genetic deletion of Vegfr2 from CECs or inhibition of VEGFA abrogates both CEC and CM proliferation. Repair of cryoinjury, a model of incomplete regeneration, displays poor spatial coupling of CEC and CM proliferation. Boosting CEC density in the border zone by injection of virus encoding Vegfa enhances CM proliferation and the efficacy of heart regeneration, suggesting that revascularization strategies to increase CEC numbers may be an important adjunct for approaches designed to promote CM proliferation after injury. Finally, we use a human Mendelian randomization study to demonstrate that circulating VEGFA levels are positively associated with higher myocardial mass among healthy individuals, suggesting similar effects on human cardiac growth. Our work demonstrates the importance of coupled CEC and CM expansion for cardiomyogenesis and reveals the presence of a myovascular niche that underlies cardiac growth and regeneration.

scholarly journals Magnetic resonance imaging of the regenerating neonatal mouse heart

2018 ◽  
Author(s):  
Mala Gunadasa-Rohling ◽  
Megan Masters ◽  
Mahon L. Maguire ◽  
Sean C. Smart ◽  
Jürgen E. Schneider ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Regenerative Process ◽  
Neonatal Mouse ◽  
Therapeutic Interventions ◽  
Mouse Heart ◽  
Coronary Artery Ligation ◽  
Heart Regeneration ◽  
Resonance Imaging ◽  
Artery Ligation

We present longitudinal magnetic resonance imaging (MRI) of neonatal mouse hearts during the first three weeks following coronary artery ligation to mimic heart attack. We confirm heart regeneration in individual animals injured on post-natal day 1 (P1) while those injured on P7 show the adult response of fibrosis, scarring and impaired heart performance. We document heart growth and development of the principal functional cardiac parameters, and also remodeling during tissue regeneration as compared to fibrosis when imaging repeatedly up to 21 days after myocardial infarction (MI). We reveal compensatory changes in cardiac function with the restoration of tissue and resolution of injury for the P1 cohort and sustained injury responses for the P7 cohort. This study resolves the controversy surrounding neonatal mouse heart regeneration and establishes a functional platform for live capture of the regenerative process and for the future testing of genetic or therapeutic interventions.

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