A5088718729- Tissue Engineering and Regenerative Medicine
- 3D Printing in Biomedical Research
- Neuroscience and Neural Engineering
- Cardiac electrophysiology and arrhythmias
- Electrospun Nanofibers in Biomedical Applications
- Pluripotent Stem Cells Research
- Angiogenesis and VEGF in Cancer
- Atherosclerosis and Cardiovascular Diseases
- Cardiovascular Disease and Adiposity
- Congenital heart defects research
- Cardiovascular Effects of Exercise
- Mesenchymal stem cell research
- Cardiac Fibrosis and Remodeling
- Extracellular vesicles in disease
- Single-cell and spatial transcriptomics
- Platelet Disorders and Treatments
- Zebrafish Biomedical Research Applications
- Cardiac pacing and defibrillation studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Receptor Mechanisms and Signaling
- Heart Rate Variability and Autonomic Control
- Cardiac Ischemia and Reperfusion
- Cardiomyopathy and Myosin Studies
- Electron Spin Resonance Studies
- Microfluidic and Bio-sensing Technologies
Brigham and Women's Hospital
2021-2025
Harvard University
2021-2025
Massachusetts Institute of Technology
2022-2025
Broad Institute
2021-2024
Johns Hopkins University
2012-2021
Johns Hopkins Medicine
2014-2021
We have developed a novel method to deliver stem cells using 3D bioprinted cardiac patches, free of biomaterials. Human induced pluripotent cell-derived cardiomyocytes (hiPSC-CMs), fibroblasts (FB) and endothelial (EC) were aggregated create mixed cell spheroids. Cardiac patches created from spheroids (CM:FB:EC = 70:15:15, 70:0:30, 45:40:15) bioprinter. analyzed with light video microscopy, immunohistochemistry, immunofluorescence, viability assays optical electrical mapping. tissue all...
Cardiovascular disease plays a central role in the electrical and structural remodeling of right atrium, predisposing to arrhythmias, heart failure, sudden death. Here, we dissect with single-nuclei RNA sequencing (snRNA-seq) spatial transcriptomics gene expression changes human ex vivo atrial tissue pericardial fluid ischemic disease, myocardial infarction, non-ischemic failure using asymptomatic patients valvular who undergo preventive surgery as control group. We reveal substantial...
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive heart condition which causes fibro-fatty myocardial scarring, arrhythmias, and sudden cardiac death. Most cases of ARVC can be linked to pathogenic mutations in the desmosome, but pathophysiology not well understood, particularly early phases when arrhythmias develop prior structural changes. Here, we created novel human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) model from patient with c.2358delA...
This protocol describes 3D bioprinting of cardiac tissue without the use biomaterials, using only cells. Cardiomyocytes, endothelial cells and fibroblasts are first isolated, counted mixed at desired cell ratios. They co-cultured in individual wells ultra-low attachment 96-well plates. Within 3 days, beating spheroids form. These then picked up by a nozzle vacuum suction assembled on needle array bioprinter. The allowed to fuse array. Three days after bioprinting, removed as an intact patch,...
In this study, we have created a multi-compartmental model replicating hierarchical vascular bed by combining two methods for vessel-on-chip preparation: viscous finger patterning and self-assembled networks.
Abstract Lung fibrosis, characterized by chronic and progressive scarring, has no cure. Hallmarks are the accumulation of myofibroblasts extracellular matrix, as well vascular remodeling. The crosstalk between vasculature is poorly understood, with conflicting reports on whether angiogenesis vessel density increased or decreased in lung fibrosis. We developed a microphysiological system that recapitulates pathophysiology fibrosis disentangles myofibroblast-vascular interactions. maintained...
The incorporation of a functional perfusable microvascular network (MVN) is common requirement for most organ on-chip-models. Long-term perfusion MVNs often required the maturation phenotypes and disease pathologies to model transport cells drugs entering organs. In our microphysiological system, we observe that flow can recover in regressed maintain at least 51 days. Throughout days, however, are continuously remodeling align with direction bulk only appear attain morphological homeostasis...
Highlights•Decellularized myocardial slices were repopulated with hiPSC-CMs to make EHS•EHS exhibited coordinated contractions and anisotropic electrical conduction•EHS cultured retained contractile function for >200 days•EHS had different sensitivities ion channel drugs than cell monolayersSummaryHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise cardiac studies, but their structural functional immaturity precludes use as faithful models of adult...
Genetic heart diseases such as arrhythmogenic cardiomyopathy (AC), a common genetic cause of sudden cardiac death, can be modeled using patient-specific induced pluripotent stem cell-derived myocytes (CMs). However, it is important to culture these cells in multicellular syncytium with exposure surrounding matrix cues create more accurate and robust models the disease due importance cell-cell cell-matrix interactions. The engineered slice, constructed by seeding CMs on intact decellularized...
This protocol describes 3D bioprinting of cardiac tissue without the use biomaterials, using only cells. Cardiomyocytes, endothelial cells and fibroblasts are first isolated, counted mixed at desired cell ratios. They co-cultured in individual wells ultra-low attachment 96-well plates. Within 3 days, beating spheroids form. These then picked up by a nozzle vacuum suction assembled on needle array bioprinter. The allowed to fuse array. Three days after bioprinting, removed as an intact patch,...
Cardiac tissue engineering approaches have the potential to regenerate functional myocardium with intrinsic vascular networks. This study compared relative effects of human adipose-derived stem/stromal cells (hASCs) and dermal fibroblasts (hDFs) in cocultures neonatal rat ventricular cardiomyocytes (NRVCMs) umbilical vein endothelial (HUVECs). At same ratios NRVCM:hASC NRVCM:hDF, hASC displayed shorter action potentials maintained capture at faster pacing rates. Similarly, coculture HUVECs,...
If a coronary blood vessel is occluded and the neighboring cardiomyocytes deprived of oxygen, subsequent reperfusion ischemic tissue can lead to oxidative damage due excessive generation reactive oxygen species. Cardiomyocytes their mitochondria are main energy producers consumers heart, metabolic changes during ischemia seem be key driver injury. Here, we hypothesized that tracking in cardiomyocyte metabolism, such as ATP concentrations, would help identifying points failure reperfusion. To...
ABSTRACT Clinically pertinent electrocardiogram (ECG) data from model systems, such as zebrafish, are crucial for illuminating factors contributing to human cardiac electrophysiological abnormalities and disease. Current zebrafish ECG collection strategies have not adequately addressed the consistent acquisition of high-quality traces or sources phenotypic variation that could obscure interpretation. Thus, we developed a novel platform ensure recording in vivo subdermal adult ECGs reading...
Abstract Ischemic heart disease is globally the leading cause of death. It plays a central role in electrical and structural remodeling right atrium, predisposing to arrhythmias, failure, sudden Here, we provide first dissection gene expression changes live atrial tissue, using single-nuclei RNA-seq spatial transcriptomics. We investigate matched samples tissue pericardial fluid reveal substantial differences disease- associated all cell types, inflammatory microvascular dysfunction...
The cardiovascular system generates and responds to mechanical forces. heartbeat pumps blood through a network of vascular tubes, which adjust their caliber in response the hemodynamic environment. However, how endothelial cells developing integrate inputs from circulatory forces into signaling pathways define vessel is poorly understood. Using vertebrate embryos
Cardiac organoids represent an important bioengineering opportunity in the development of models to study human heart pathophysiology. By incorporating multiple cardiac cell types three-dimensional culture and developmentally-guided biochemical signaling, recapitulate numerous features tissue. However, tissue also experiences a variety mechanical forces as develops over course each contraction cycle. It is now clear that these impact cellular specification, phenotype, function, should be...
Abstract Shear stress generated by the flow of blood in vasculature is a potent regulator endothelial cell phenotype and vascular structure. While responses to are complex context-dependent, signaling response shear induced laminar flows coordinated transcription factor KLF2. The expression KLF2 cells associated with quiescent, anti-inflammatory has been well characterized two-dimensional systems, but not studied three-dimensional vitro systems. Here we develop engineered microvascular...
Type 2 long QT (LQT2) syndrome is a cardiac disorder associated with hERG channel mutation that may lead to tachyarrhythmia and sudden death. We developed syncytial model of cardiomyocytes (CMs) differentiated from iPS cells derived an LQT2 patient harboring A422T mutation. The has been shown cause marked decrease in IKr current mainly due trafficking defect the channel. Immunostaining cTnI revealed CMs were isotropically distributed well-formed sarcomeres. Both wild type (WT) monolayers...