A5028806508- Electrospun Nanofibers in Biomedical Applications
- Tissue Engineering and Regenerative Medicine
- Infectious Aortic and Vascular Conditions
- Atherosclerosis and Cardiovascular Diseases
- Aortic Disease and Treatment Approaches
- Transplantation: Methods and Outcomes
- Cardiac and Coronary Surgery Techniques
- Renal Transplantation Outcomes and Treatments
- Mesenchymal stem cell research
- Coronary Interventions and Diagnostics
- Cell Adhesion Molecules Research
- Cardiac Valve Diseases and Treatments
- T-cell and B-cell Immunology
- Aortic aneurysm repair treatments
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Signaling Pathways in Disease
- Organ Transplantation Techniques and Outcomes
- Angiogenesis and VEGF in Cancer
- Congenital heart defects research
- Congenital Heart Disease Studies
- Immune cells in cancer
- Extracellular vesicles in disease
- Electron and X-Ray Spectroscopy Techniques
Nationwide Children's Hospital
2016-2025
Yanbian University
2025
Sun Yat-sen University
2023-2024
Sun Yat-sen University Cancer Center
2023-2024
Council of Agriculture
2024
Yale University
2007-2017
Gunze (Japan)
2017
Young Invincibles
2012-2016
VA Connecticut Healthcare System
2015
Peking University People's Hospital
2015
Because adult lung tissue has limited regeneration capacity, transplantation is the primary therapy for severely damaged lungs. To explore whether can be regenerated in vitro, we treated lungs from rats using a procedure that removes cellular components but leaves behind scaffold of extracellular matrix retains hierarchical branching structures airways and vasculature. We then used bioreactor to culture pulmonary epithelium vascular endothelium on acellular matrix. The seeded displayed...
Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are the earliest tissue-engineered vascular grafts (TEVGs) to be used clinically. These TEVGs transform into living blood vessels in vivo, an endothelial cell (EC) lining invested by smooth muscle (SMCs); however, process which this occurs is unclear. To test if BMCs differentiate mature of neovessel, we implanted immunodeficient mouse recipient human BMC (hBMC)-seeded scaffolds. As humans, a host as venous...
Maintenance of normal endothelial function is critical to various aspects blood vessel function, but its regulation poorly understood. In this study, we show that disruption baseline fibroblast growth factor (FGF) signaling the endothelium leads a dramatic reduction in let-7 miRNA levels that, turn, increases expression transforming (TGF)-β ligands and receptors activation TGF-β signaling, leading endothelial-to-mesenchymal transition (Endo-MT). We also find Endo-MT an important driver...
Tissue engineered vascular grafts (TEVGs) have the potential to overcome issues faced by existing small diameter prosthetic providing a biodegradable scaffold where patient's own cells can engraft and form functional neotissue. However, applying classical approaches create arterial TEVGs using slow degrading materials with supraphysiological mechanical properties, typically results in limited host cell infiltration, poor remodeling, stenosis, calcification. The purpose of this study is...
The primary graft-related complication during the first clinical trial evaluating use of tissue-engineered vascular grafts (TEVGs) was stenosis. We investigated role macrophages in formation TEVG stenosis a murine model. analyzed natural history macrophage infiltration at critical time points and evaluated cell seeding on neovessel formation. To assess function infiltrating macrophages, we implanted TEVGs into mice that had been depleted using clodronate liposomes. confirm this, used...
Congenital heart defect interventions may benefit from the fabrication of patient-specific vascular grafts because wide array anatomies present in children with cardiovascular defects. 3D printing is used to establish a platform for production custom grafts, which are biodegradable, mechanically compatible tissues, and support neotissue formation growth. As service our authors readers, this journal provides supporting information supplied by authors. Such materials peer reviewed be...
We developed a tissue-engineered vascular graft composed of biodegradable scaffold seeded with autologous bone marrow-derived mononuclear cells (BMMCs) that is currently in clinical trial and analogous mouse models to study mechanisms neovessel formation. previously reported human BMMCs were rapidly lost after implantation into immunodeficient mice as host macrophages invaded the graft. As consequence, resulting was entirely cell origin. Here, we investigate source neotissue syngeneic...
Cardiac allograft vasculopathy is the major cause of late loss after heart transplantation. lesions contain alloreactive T cells that secrete interferon-γ, a vasculopathic cytokine, and occur more frequently in patients with donor-specific antibody. Pathological interactions between these immune effectors, representing cellular humoral immunity, respectively, remain largely unexplored.We used human panel reactive antibody to form membrane attack complexes on allogeneic endothelial vitro...
Interferon (IFN)-γ, a cytokine characteristically expressed in arteriosclerotic diseases, acts directly on vascular smooth muscle cells to induce cellular proliferation and intimal expansion. Signaling by the mammalian target of rapamycin raptor complex, known as mTORC1, is associated with cell growth active within lesions but not be triggered proinflammatory factors cells. We investigated mechanisms for proarteriosclerotic effects IFN-γ absence leukocytes exploiting species specificity this...
The first clinical trial of tissue-engineered vascular grafts (TEVGs) identified stenosis as the primary cause graft failure. In this study, we aimed to elucidate role host immune response in development using a murine model TEVG implantation. We found that C.B-17 wild-type (WT) mouse (control) undergoes dramatic stenotic response, which is nearly completely abolished immunodeficient SCID/beige (bg) variant. SCID mice, lack an adaptive system due absence T and B lymphocytes, experienced...
Surface modification of biodegradable vascular grafts is an important strategy to improve the in situ endothelialization tissue engineered (TEVGs) and prevent major complications associated with current synthetic grafts. Important strategies for improving include increasing endothelial cell mobilization increased capture through biofunctionalization TEVGs. The objective this study was assess two polyester These techniques consisted cross-linking heparin graft surfaces immobilize growth...
Neuroblastoma, the most common extracranial solid tumor in childhood, remains a therapeutic challenge. However, one promising patient treatment strategy is delivery of anti-tumor agents via mesenchymal stromal cell (MSC) therapy. MSCs have been safely used to treat genetic bone diseases such as osteogenesis imperfecta, cardiovascular diseases, autoimmune and cancer. The pro-inflammatory cytokine interferon-gamma (IFNγ) has shown decrease proliferation by altering microenvironment (TME)....
Allograft vascular dysfunction predisposes to arteriosclerosis and graft loss. We examined how develops in transplanted human arteries response circulating allogeneic T cells vivo using immunodeficient murine hosts. Within 7–9 days, developed endothelial cell (EC) but remained sensitive exogenous NO. By 2 weeks, the grafts impaired contractility desensitization NO, both signs of VSMC dysfunction. These cell–dependent changes correlated with loss eNOS expression iNOS — latter predominantly...
Interleukin (IL) 1alpha produced by human endothelial cells (ECs), in response to tumor necrosis factor (TNF) or co-culture with allogeneic T a TNF-dependent manner, can augment the release of cytokines from alloreactive memory vitro. In human-mouse chimeric model artery allograft rejection, ECs lining transplanted arteries express IL-1alpha, and blocking IL-1 reduces extent cell infiltration into intima selectively inhibits IL-17 production infiltrating cells. skin grafts implanted on...
Microcirculation (2010) 17, 367–380. doi: 10.1111/j.1549-8719.2010.00038.x Abstract Objective: Pericytes are critical cellular components of the microvasculature that play a major role in vascular development and pathologies, yet their study has been hindered by lack standardized method for isolation growth. Here we report culturing human pericytes from readily available tissue source, placenta, provide thorough characterization resultant cell populations. Methods: We developed an optimized...
Human graft endothelial cells (ECs) can act as antigen-presenting to initiate allograft rejection by host memory T cells. Rapamycin, an mTOR inhibitor used clinically suppress cell responses, also acts on DCs, rendering them tolerogenic. Here, we report the effects of rapamycin EC alloimmunogenicity. Compared with mock-treated cells, rapamycin-pretreated human ECs (rapa-ECs) stimulated less proliferation and cytokine secretion from allogeneic CD4+ effect mimicked shRNA knockdown or raptor in...
The surgical repair of heart and vascular disease often requires implanting synthetic grafts. While grafts have been successfully used for medium-to-large sized arteries, applications small diameter arteries (<6 mm) is limited due to high rates occlusion by thrombosis. Our objective was develop a tissue engineered graft (TEVG) arteries. TEVGs composed polylactic acid nanofibers with inner luminal between 0.5 0.6 mm were surgically implanted as infra-renal aortic interposition conduits in 25...
Abstract Perioperative injuries to an allograft exacerbate graft rejection, which in humans is primarily mediated by effector memory T cells. IL-6 transcripts human coronary artery segments rapidly increase posttransplantation into immunodeficient mouse hosts compared with those of pretransplant specimens and fall dramatically 30 d. Adoptive transfer PBMCs allogeneic the 2 d postoperatively results cell infiltrates intimal expansion 4 wk later. Ab neutralization reduces magnitude total...