Hung-fat Tse - Academia.edu (original) (raw)
Papers by Hung-fat Tse
International Journal of Molecular Sciences
Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by MeCP2 mutations. Nonetheles... more Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by MeCP2 mutations. Nonetheless, the pathophysiological roles of MeCP2 mutations in the etiology of intrinsic cardiac abnormality and sudden death remain unclear. In this study, we performed a detailed functional studies (calcium and electrophysiological analysis) and RNA-sequencing-based transcriptome analysis of a pair of isogenic RTT female patient-specific induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs) that expressed either MeCP2wildtype or MeCP2mutant allele and iPSC-CMs from a non-affected female control. The observations were further confirmed by additional experiments, including Wnt signaling inhibitor treatment, siRNA-based gene silencing, and ion channel blockade. Compared with MeCP2wildtype and control iPSC-CMs, MeCP2mutant iPSC-CMs exhibited prolonged action potential and increased frequency of spontaneous early after polarization. RNA sequencing analysis revealed up-regulation of various...
International Journal of Molecular Sciences
Cardiac shock wave therapy (CSWT) is a novel therapeutic procedure for patients with angina that ... more Cardiac shock wave therapy (CSWT) is a novel therapeutic procedure for patients with angina that is refractory to conventional therapy. We investigated the potential mechanism and therapeutic efficacy of non-R-wave-triggered CSWT to attenuate myocardial dysfunction in a large animal model of hypertensive cardiomyopathy. Sustained elevated blood pressure (BP) was induced in adult pigs using a combination of angiotensin-II and deoxycorticosterone acetate (DOCA). Two sessions of non-R-wave-triggered CSWT were performed at 11 and 16 weeks. At 10 weeks, systolic and diastolic blood pressure, LV posterior wall thickness and intraventricular septum thickness significantly increased in both the hypertension and CSWT groups. At 20 weeks, +dP/dt and end-systolic pressure-volume relationship (ESPVR) decreased significantly in the hypertension group but not the CSWT group, as compared with week 10. A significant improvement in end-diastolic pressure-volume relationship (EDPVR) was observed in t...
Journal of the Hong Kong College of Cardiology
Frontiers in Cardiovascular Medicine
Stem Cell Research & Therapy, 2021
Background The creation of a bioengineered cardiac patch (BCP) is a potential novel strategy for ... more Background The creation of a bioengineered cardiac patch (BCP) is a potential novel strategy for myocardial repair. Nevertheless, the ideal scaffold for BCP is unknown. Objective We investigated whether the decellularized placenta (DP) could serve as natural scaffold material to create a BCP for myocardial repair. Methods and results A BCP was created by seeding human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs; 1 × 106/cm2) onto DP. The functional and electrophysiological properties of the BCP were first characterized by in vitro analysis and optical mapping. Next, in vivo therapeutic efficacy of the BCP was evaluated in a rat model of myocardial infarction (MI), created by left descending coronary artery ligation (MI + BCP group), and compared with MI alone (MI group), transplantation of DP (MI + DP group), and hiPSC-CMs (MI + CM group). Cytokine profiling demonstrated that the BCP contained multiple growth and angiogenic factors, including vascular endothelial...
European Heart Journal, 2013
We sought to demonstrate whether therapeutic efficacy can be improved by combination of repeated ... more We sought to demonstrate whether therapeutic efficacy can be improved by combination of repeated intravenous administration and local transplantation of human induced pluripotential stem cell derived MSCs (hiPSC-MSCs). In this study, mice model of hind-limb ischemia was established by ligation of left femoral artery. hiPSC-MSCs (5x105) was intravenously administrated immediately after induction of hind limb ischemia with or without following intravenous administration of hiPSC-MSCs every week or every 3 days. Intramuscular transplantation of hiPSC-MSCs (3x106) was performed one week after induction of hind-limb ischemia. We compared the therapeutic efficacy and cell survival of intramuscular transplantation of hiPSC-MSCs with or without a single or repeated intravenous administration of hiPSC-MSCs. Repeated intravenous administration of hiPSC-MSCs could increase splenic regulatory T cells (Tregs) activation, decrease splenic natural killer (NK) cells expression, promote the polariza...
PLOS ONE, 2021
BackgroundA high proportion of COVID-19 patients were reported to have cardiac involvements. Data... more BackgroundA high proportion of COVID-19 patients were reported to have cardiac involvements. Data pertaining to cardiac sequalae is of urgent importance to define subsequent cardiac surveillance.MethodsWe performed a systematic cardiac screening for 97 consecutive COVID-19 survivors including electrocardiogram (ECG), echocardiography, serum troponin and NT-proBNP assay 1–4 weeks after hospital discharge. Treadmill exercise test and cardiac magnetic resonance imaging (CMR) were performed according to initial screening results.ResultsThe mean age was 46.5 ± 18.6 years; 53.6% were men. All were classified with non-severe disease without overt cardiac manifestations and did not require intensive care. Median hospitalization stay was 17 days and median duration from discharge to screening was 11 days. Cardiac abnormalities were detected in 42.3% including sinus bradycardia (29.9%), newly detected T-wave abnormality (8.2%), elevated troponin level (6.2%), newly detected atrial fibrillatio...
Circulation, 2016
Background: Danon disease is an X-linked disorder that leads to fatal cardiomyopathy caused by a ... more Background: Danon disease is an X-linked disorder that leads to fatal cardiomyopathy caused by a deficiency in lysosome-associated membrane protein-2 (LAMP2). In female patients, a later onset and less severe clinical phenotype have been attributed to the random inactivation of the X chromosome carrying the mutant diseased allele. We generated a patient-specific induced pluripotent stem cell (iPSCs)–based model of Danon disease to evaluate the therapeutic potential of Xi-chromosome reactivation using a DNA methylation inhibitor. Methods: Using whole-exome sequencing, we identified a nonsense mutation (c.520C>T, exon 4) of the LAMP2 gene in a family with Danon disease. We generated iPSC lines from somatic cells derived from the affected mother and her 2 sons, and we then differentiated them into cardiomyocytes (iPSC-CMs) for modeling the histological and functional signatures, including autophagy failure of Danon disease. Results: Our iPSC-CM platform provides evidence that random...
Cell death & disease, Jan 21, 2015
Mesenchymal stem cell (MSC) transplantation has achieved only modest success in the treatment of ... more Mesenchymal stem cell (MSC) transplantation has achieved only modest success in the treatment of ischemic heart disease owing to poor cell viability in the diseased microenvironment. Activation of the NRG1 (neuregulin1)-ERBB4 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) signaling pathway has been shown to stimulate mature cardiomyocyte cell cycle re-entry and cell division. In this connection, we aimed to determine whether overexpression of ERBB4 in MSCs can enhance their cardio-protective effects following myocardial infarction. NRG1, MSCs or MSC-ERBB4 (MSC with ERBB4 overexpression), were transplanted into mice following myocardial infarction. Superior to that of MSCs and solely NRG1, MSC-ERBB4 transplantation significantly preserved heart functions accompanied with reduced infarct size, enhanced cardiomyocyte division and less apoptosis during early phase of infarction. The transduction of ERBB4 into MSCs indeed increased cell mobility and apoptotic resistanc...
Tissue Engineering Part A, 2014
Journal of the American College of Cardiology, 2006
European Heart Journal, 2007
Diabetes Care, 2012
OBJECTIVE Diabetes mellitus (DM) is a well-established risk factor for coronary artery disease. N... more OBJECTIVE Diabetes mellitus (DM) is a well-established risk factor for coronary artery disease. Nonetheless, it remains unclear whether DM contributes to sudden cardiac death in patients who survive myocardial infarction (MI). The objective of this study was to compare the incidence of sudden cardiac death post-MI in diabetic and nondiabetic patients with no residual myocardial ischemia. RESEARCH DESIGN AND METHODS A total of 610 consecutive post-MI patients referred to a cardiac rehabilitation program with negative exercise stress test were studied. RESULTS Of these, 236 patients had DM at baseline. Over a mean follow-up of 5 years, 67 patients with DM (28.4%) and 76 of 374 patients without DM (20.2%) had died with a hazard ratio (HR) of 1.74 (95% CI: 1.28–2.56; P < 0.001). Patients with DM also had a higher incidence of cardiac death (1.84 [1.16–3.21]; P = 0.01), principally due to a higher incidence of sudden cardiac death (2.14 [1.22–4.23]; P < 0.001). Multiple Cox regress...
Circulation Journal, 2012
International Journal of Molecular Sciences
Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by MeCP2 mutations. Nonetheles... more Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by MeCP2 mutations. Nonetheless, the pathophysiological roles of MeCP2 mutations in the etiology of intrinsic cardiac abnormality and sudden death remain unclear. In this study, we performed a detailed functional studies (calcium and electrophysiological analysis) and RNA-sequencing-based transcriptome analysis of a pair of isogenic RTT female patient-specific induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs) that expressed either MeCP2wildtype or MeCP2mutant allele and iPSC-CMs from a non-affected female control. The observations were further confirmed by additional experiments, including Wnt signaling inhibitor treatment, siRNA-based gene silencing, and ion channel blockade. Compared with MeCP2wildtype and control iPSC-CMs, MeCP2mutant iPSC-CMs exhibited prolonged action potential and increased frequency of spontaneous early after polarization. RNA sequencing analysis revealed up-regulation of various...
International Journal of Molecular Sciences
Cardiac shock wave therapy (CSWT) is a novel therapeutic procedure for patients with angina that ... more Cardiac shock wave therapy (CSWT) is a novel therapeutic procedure for patients with angina that is refractory to conventional therapy. We investigated the potential mechanism and therapeutic efficacy of non-R-wave-triggered CSWT to attenuate myocardial dysfunction in a large animal model of hypertensive cardiomyopathy. Sustained elevated blood pressure (BP) was induced in adult pigs using a combination of angiotensin-II and deoxycorticosterone acetate (DOCA). Two sessions of non-R-wave-triggered CSWT were performed at 11 and 16 weeks. At 10 weeks, systolic and diastolic blood pressure, LV posterior wall thickness and intraventricular septum thickness significantly increased in both the hypertension and CSWT groups. At 20 weeks, +dP/dt and end-systolic pressure-volume relationship (ESPVR) decreased significantly in the hypertension group but not the CSWT group, as compared with week 10. A significant improvement in end-diastolic pressure-volume relationship (EDPVR) was observed in t...
Journal of the Hong Kong College of Cardiology
Frontiers in Cardiovascular Medicine
Stem Cell Research & Therapy, 2021
Background The creation of a bioengineered cardiac patch (BCP) is a potential novel strategy for ... more Background The creation of a bioengineered cardiac patch (BCP) is a potential novel strategy for myocardial repair. Nevertheless, the ideal scaffold for BCP is unknown. Objective We investigated whether the decellularized placenta (DP) could serve as natural scaffold material to create a BCP for myocardial repair. Methods and results A BCP was created by seeding human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs; 1 × 106/cm2) onto DP. The functional and electrophysiological properties of the BCP were first characterized by in vitro analysis and optical mapping. Next, in vivo therapeutic efficacy of the BCP was evaluated in a rat model of myocardial infarction (MI), created by left descending coronary artery ligation (MI + BCP group), and compared with MI alone (MI group), transplantation of DP (MI + DP group), and hiPSC-CMs (MI + CM group). Cytokine profiling demonstrated that the BCP contained multiple growth and angiogenic factors, including vascular endothelial...
European Heart Journal, 2013
We sought to demonstrate whether therapeutic efficacy can be improved by combination of repeated ... more We sought to demonstrate whether therapeutic efficacy can be improved by combination of repeated intravenous administration and local transplantation of human induced pluripotential stem cell derived MSCs (hiPSC-MSCs). In this study, mice model of hind-limb ischemia was established by ligation of left femoral artery. hiPSC-MSCs (5x105) was intravenously administrated immediately after induction of hind limb ischemia with or without following intravenous administration of hiPSC-MSCs every week or every 3 days. Intramuscular transplantation of hiPSC-MSCs (3x106) was performed one week after induction of hind-limb ischemia. We compared the therapeutic efficacy and cell survival of intramuscular transplantation of hiPSC-MSCs with or without a single or repeated intravenous administration of hiPSC-MSCs. Repeated intravenous administration of hiPSC-MSCs could increase splenic regulatory T cells (Tregs) activation, decrease splenic natural killer (NK) cells expression, promote the polariza...
PLOS ONE, 2021
BackgroundA high proportion of COVID-19 patients were reported to have cardiac involvements. Data... more BackgroundA high proportion of COVID-19 patients were reported to have cardiac involvements. Data pertaining to cardiac sequalae is of urgent importance to define subsequent cardiac surveillance.MethodsWe performed a systematic cardiac screening for 97 consecutive COVID-19 survivors including electrocardiogram (ECG), echocardiography, serum troponin and NT-proBNP assay 1–4 weeks after hospital discharge. Treadmill exercise test and cardiac magnetic resonance imaging (CMR) were performed according to initial screening results.ResultsThe mean age was 46.5 ± 18.6 years; 53.6% were men. All were classified with non-severe disease without overt cardiac manifestations and did not require intensive care. Median hospitalization stay was 17 days and median duration from discharge to screening was 11 days. Cardiac abnormalities were detected in 42.3% including sinus bradycardia (29.9%), newly detected T-wave abnormality (8.2%), elevated troponin level (6.2%), newly detected atrial fibrillatio...
Circulation, 2016
Background: Danon disease is an X-linked disorder that leads to fatal cardiomyopathy caused by a ... more Background: Danon disease is an X-linked disorder that leads to fatal cardiomyopathy caused by a deficiency in lysosome-associated membrane protein-2 (LAMP2). In female patients, a later onset and less severe clinical phenotype have been attributed to the random inactivation of the X chromosome carrying the mutant diseased allele. We generated a patient-specific induced pluripotent stem cell (iPSCs)–based model of Danon disease to evaluate the therapeutic potential of Xi-chromosome reactivation using a DNA methylation inhibitor. Methods: Using whole-exome sequencing, we identified a nonsense mutation (c.520C>T, exon 4) of the LAMP2 gene in a family with Danon disease. We generated iPSC lines from somatic cells derived from the affected mother and her 2 sons, and we then differentiated them into cardiomyocytes (iPSC-CMs) for modeling the histological and functional signatures, including autophagy failure of Danon disease. Results: Our iPSC-CM platform provides evidence that random...
Cell death & disease, Jan 21, 2015
Mesenchymal stem cell (MSC) transplantation has achieved only modest success in the treatment of ... more Mesenchymal stem cell (MSC) transplantation has achieved only modest success in the treatment of ischemic heart disease owing to poor cell viability in the diseased microenvironment. Activation of the NRG1 (neuregulin1)-ERBB4 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) signaling pathway has been shown to stimulate mature cardiomyocyte cell cycle re-entry and cell division. In this connection, we aimed to determine whether overexpression of ERBB4 in MSCs can enhance their cardio-protective effects following myocardial infarction. NRG1, MSCs or MSC-ERBB4 (MSC with ERBB4 overexpression), were transplanted into mice following myocardial infarction. Superior to that of MSCs and solely NRG1, MSC-ERBB4 transplantation significantly preserved heart functions accompanied with reduced infarct size, enhanced cardiomyocyte division and less apoptosis during early phase of infarction. The transduction of ERBB4 into MSCs indeed increased cell mobility and apoptotic resistanc...
Tissue Engineering Part A, 2014
Journal of the American College of Cardiology, 2006
European Heart Journal, 2007
Diabetes Care, 2012
OBJECTIVE Diabetes mellitus (DM) is a well-established risk factor for coronary artery disease. N... more OBJECTIVE Diabetes mellitus (DM) is a well-established risk factor for coronary artery disease. Nonetheless, it remains unclear whether DM contributes to sudden cardiac death in patients who survive myocardial infarction (MI). The objective of this study was to compare the incidence of sudden cardiac death post-MI in diabetic and nondiabetic patients with no residual myocardial ischemia. RESEARCH DESIGN AND METHODS A total of 610 consecutive post-MI patients referred to a cardiac rehabilitation program with negative exercise stress test were studied. RESULTS Of these, 236 patients had DM at baseline. Over a mean follow-up of 5 years, 67 patients with DM (28.4%) and 76 of 374 patients without DM (20.2%) had died with a hazard ratio (HR) of 1.74 (95% CI: 1.28–2.56; P < 0.001). Patients with DM also had a higher incidence of cardiac death (1.84 [1.16–3.21]; P = 0.01), principally due to a higher incidence of sudden cardiac death (2.14 [1.22–4.23]; P < 0.001). Multiple Cox regress...
Circulation Journal, 2012