A5053549326- Electrospun Nanofibers in Biomedical Applications
- Tissue Engineering and Regenerative Medicine
- Mesenchymal stem cell research
- Pluripotent Stem Cells Research
- Angiogenesis and VEGF in Cancer
- 3D Printing in Biomedical Research
- Congenital heart defects research
- Cell Adhesion Molecules Research
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- Bone Tissue Engineering Materials
- Cardiac tumors and thrombi
- Mitochondrial Function and Pathology
- Cardiac Fibrosis and Remodeling
- Zebrafish Biomedical Research Applications
- Neurogenetic and Muscular Disorders Research
- Proteoglycans and glycosaminoglycans research
- Autophagy in Disease and Therapy
- Chemokine receptors and signaling
- Pulmonary Hypertension Research and Treatments
- Long-Term Effects of COVID-19
- Kruppel-like factors research
- COVID-19 Clinical Research Studies
- Immune cells in cancer
- Sirtuins and Resveratrol in Medicine
Boston Children's Hospital
2019-2024
Harvard University
2019-2024
AstraZeneca (Sweden)
2023-2024
Boston Children's Museum
2019-2020
King's College London
2015-2019
British Heart Foundation
2013-2018
King's College School
2018
Centre for Human Genetics
2013
Shanghai Institutes for Biological Sciences
2013
Chinese Academy of Sciences
2013
Temporal activation of ETV2 enables robust differentiation human pluripotent stem cells into competent endothelial cells.
Rationale: Smooth muscle cells (SMCs) are a key component of tissue-engineered vessels. However, the sources by which they can be isolated limited. Objective: We hypothesized that large number SMCs could obtained direct reprogramming fibroblasts, is, differentiation specific cell lineages before reaching pluripotent state. Methods and Results: designed combined protocol human neonatal lung fibroblasts. Four factors (OCT4, SOX2, KLF4, cMYC) were overexpressed in fibroblasts under conditions...
Islet transplantation has been established as a viable treatment modality for type 1 diabetes. However, the side effects of systemic immunosuppression required patients often outweigh its benefits. Here, we engineer programmed death ligand-1 and cytotoxic T lymphocyte antigen 4 immunoglobulin fusion protein–modified mesenchymal stromal cells (MSCs) accessory islet cotransplantation. The engineered MSCs (eMSCs) improved outcome both syngeneic allogeneic in diabetic mice resulted allograft...
Abstract Severe viral pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized a hyperinflammatory state typified elevated circulating pro-inflammatory cytokines, frequently leading to potentially lethal vascular complications including thromboembolism, disseminated intracellular coagulopathy and vasculitis. Though endothelial infection subsequent damage have been described in patients with fatal COVID-19, mechanism which this occurs remains...
Deciphering the extracellular signals that regulate SMC differentiation from stem cells is vital to further our understanding of pathogenesis vascular disease and for development cell-based therapies tissue engineering. Hyaluronan (HA) has emerged as an important component cell niche, however its role during a complicated inadequately defined process. This study aimed investigate HA in embryonic (ESC) toward lineage. ESCs were seeded on collagen-IV medium generate ESC-derived SMCs (esSMCs)....
Abstract Endothelial dysfunction is widely implicated in cardiovascular pathological changes and development of vascular disease. In view the fact that spontaneous endothelial cell (EC) regeneration a slow insufficient process, it great interest to explore alternative sources capable generating functional ECs. Vascular smooth muscle (SMC) composes majority wall retains phenotypic plasticity response various stimuli. The aim this study test feasibility conversion SMC into EC through use...
Vascular adventitial Sca1+ (stem cell antigen-1) progenitor cells preferentially differentiate into smooth muscle cells, which contribute to vascular remodeling and neointima formation in vessel grafts. Therefore, directing the differentiation of toward endothelial lineage could represent a new therapeutic strategy against disease.We thus developed fast, reproducible protocol based on single-gene transfer ETV2 (ETS variant 2) fate studied effect conversion hyperplasia model injury. After...
Background and Purpose Vessel graft failure is typically associated with arteriosclerosis, in which endothelial dysfunction/damage a key event. Resveratrol has been shown to possess cardioprotective capacity reduce atherosclerosis. We aimed study the influence of resveratrol on behavior resident stem cells that may contribute arteriosclerosis. Experimental Approach Vascular progenitor embryonic were treated under differentiating conditions markers expression was evaluated. Expression miR-21...
The development of decellularised scaffolds for small diameter vascular grafts is hampered by their limited patency, due to the lack luminal cell coverage endothelial cells (EC) and low tone vessel absence a contractile smooth muscle (SMC). In this study, we identify population progenitor c-Kit+/Sca-1- available in large numbers derived from immuno-privileged embryonic stem (ESCs). We also define an efficient controlled differentiation protocol yielding fully differentiated ECs SMCs...
Objective— To determine the role of a cytokine-like protein DKK3 (dikkopf-3) in directly transdifferentiating fibroblasts into endothelial cells (ECs) and underlying mechanisms. Approach Results— overexpression human under defined conditions for 4 days led to notable change cell morphology progenitor gene expression. It was revealed that these went through mesenchymal-to-epithelial transition subsequently expressed KDR (kinase insert domain receptor) at high levels. Further culture EC media...
Regeneration of large bones remains a challenge in surgery. Recent developmental engineering efforts aim to recapitulate endochondral ossification (EO), critical step bone formation. However, this process entails the condensation mesenchymal stem cells (MSCs) into cartilaginous templates, which requires long-term cultures and is challenging scale up. Here, biomimetic scaffold developed that allows rapid self-sustained EO without initial hypertrophic chondrogenesis. The design comprises...
Abstract Reduced mitochondrial function increases myocardial susceptibility to ischemia–reperfusion injury (IRI) in diabetic hearts. Mitochondrial transplantation (MT) ameliorates IRI, however, the cardioprotective effects of MT may be limited using mitochondria. Zucker Diabetic Fatty (ZDF) rats were subjected temporary RI and then received either vehicle alone or containing mitochondria isolated from ZDF non-diabetic lean (ZL) rats. The allowed recover for 2 h 28 days. ZDF- ZL-mitochondria...
Induced pluripotent stem cell (iPSC) derived endothelial cells (iECs) have emerged as a promising tool for studying vascular biology and providing platform modelling various diseases, including those with genetic origins. Currently, primary ECs are the main source disease in this field. However, they difficult to edit limited lifespan. To study effects of targeted mutations on an endogenous level, we generated characterized iPSC model venous malformations (VMs). CRISPR-Cas9 technology was...
Cell transplantation success for myocardial infarction (MI) treatment is often hindered by low engraftment due to washout effects during contraction. A clinically viable biomaterial that enhances cell retention can optimize intramyocardial delivery. In this study, a therapeutic delivery method developed MI utilizing photocrosslinkable gelatin methacryloyl (GelMA) hydrogel. Human vascular progenitor cells, capable of forming functional vasculatures upon transplantation, are combined with an...
Key Points HA-specific iPSC-derived ECs overexpress full-length F8 after genetic engineering via a piggyBac transposon system. Bioengineered microvascular grafts deliver FVIII into the bloodstream and restore hemostasis in hemophilic SCID mice.
The construction of vascular conduits is a fundamental strategy for surgical repair damaged and injured vessels resulting from cardiovascular diseases. current protocol presents an efficient reproducible in which functional tissue engineered vessel grafts can be generated using partially induced pluripotent stem cell (PiPSC) human fibroblasts. We designed decellularized scaffold bioreactor, closely mimics the matrix protein structure blood flow that exists within native vessel, seeding...
Endocardial fibroelastosis (EFE) is defined by fibrotic tissue on the endocardium and forms partly through aberrant endothelial-to-mesenchymal transition. However, pathologic triggers are still unknown. In this study, we showed that abnormal flow induces EFE transition in a rodent model, losartan can abrogate development. Furthermore, translated our findings to human endocardial endothelial cells, laminar promotes suppression of genes associated with mesenchymal differentiation. These...
The construction of vascular conduits is a fundamental strategy for surgical repair damaged and injured vessels resulting from cardiovascular diseases. current protocol presents an efficient reproducible in which functional tissue engineered vessel grafts can be generated using partially induced pluripotent stem cell (PiPSC) human fibroblasts. We designed decellularized scaffold bioreactor, closely mimics the matrix protein structure blood flow that exists within native vessel, seeding...
ABSTRACT Human induced pluripotent stem cell (h-iPSC)–derived endothelial cells (h-iECs) have become a valuable tool in regenerative medicine. However, current differentiation protocols remain inefficient and lack reliability. Here, we describe method for rapid, consistent, highly efficient generation of h-iECs. The protocol entails the delivery modified mRNA encoding transcription factor ETV2 at intermediate mesodermal stage differentiation. This approach reproducibly differentiated...