A5035583067- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Tissue Engineering and Regenerative Medicine
- Virus-based gene therapy research
- Electrospun Nanofibers in Biomedical Applications
- Orthopedic Surgery and Rehabilitation
- Xenotransplantation and immune response
- Elbow and Forearm Trauma Treatment
- Pancreatic function and diabetes
- Shoulder and Clavicle Injuries
- Single-cell and spatial transcriptomics
- Renal and related cancers
- Asthma and respiratory diseases
- 3D Printing in Biomedical Research
- T-cell and B-cell Immunology
- Mesenchymal stem cell research
- CAR-T cell therapy research
- Urticaria and Related Conditions
- Congenital heart defects research
- Ureteral procedures and complications
- Hematopoietic Stem Cell Transplantation
- Immune Response and Inflammation
- Total Knee Arthroplasty Outcomes
- Orthopaedic implants and arthroplasty
- Congenital limb and hand anomalies
University of Wisconsin–Madison
2016-2025
American Society of Transplantation
2022
Morgridge Institute for Research
2017-2019
Case Western Reserve University
2014
Basingstoke and North Hampshire Hospital
2013
Newcastle University
2011
Cellular Dynamics International (United States)
2010-2011
Virginia Mason Medical Center
2008
Stanford University
2006
Extracellular matrix (ECM) plays an important developmental role by regulating cell behaviour through structural and biochemical stimulation. Tissue-specific ECM, attained decellularization, has been proposed in several strategies for tissue organ replacement. Decellularization of animal pancreata reported, but the same methods applied to human pancreas are less effective due higher lipid content. Moreover, ECM-derived hydrogels can be obtained from many decellularized tissues, have not...
In this study, we demonstrate a newly derived mouse model that supports engraftment of human hematopoietic stem cells (HSCs) in the absence irradiation. We cross NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NSG) strain with C57BL/6J-Kit(W-41J)/J (C57BL/6.Kit(W41)) and engraft, without irradiation, resulting NBSGW cord blood CD34+ cells. At 12-weeks postengraftment mice, observe cell chimerism marrow (97% ± 0.4%), peripheral (61% 2%), spleen (94% 2%) at levels observed irradiation NSG mice. also...
Macrophages armed with chimeric antigen receptors (CARs) provide a potent new option for treating solid tumors. However, genetic engineering and scalable production of somatic macrophages remains significant challenges. Here, we used CRISPR-Cas9 gene editing methods to integrate an anti-GD2 CAR into the AAVS1 locus human pluripotent stem cells (hPSCs). We then established serum- feeder-free differentiation protocol generating (CAR-Ms) through arterial endothelial-to-hematopoietic transition...
Induced pluripotent stem cells (iPSCs) hold enormous potential for the development of personalized in vitro disease models, genomic health analyses, and autologous cell therapy. Here we describe generation T lymphocyte-derived iPSCs from small, clinically advantageous volumes non-mobilized peripheral blood. These T-cell derived ("TiPS") retain a normal karyotype genetic identity to donor. They share common characteristics with human embryonic (hESCs) respect morphology,...
Significance Generating fully functional arterial endothelial cells is a critical problem for vascular development and disease research. Currently, the derived from human pluripotent stem lack range of arterial-specific functions in vitro protective function ischemic tissues vivo. Here, we combine single-cell RNA sequencing CRISPR-Cas9 technology to identify pathways regulating cell differentiation. We then manipulate these generate that demonstrate unprecedented as well improve survival...
Primary human vocal fold mucosal cells recapitulate native physiologic function, offering voice restoration to patients with advanced laryngeal disease.
Highlights•Neonatal tissue is a viable alternative to fetal for mouse humanization•Over 1,000 NeoThy mice can be made from one neonatal thymus donor•The enables robust pre-clinical immunogenicity studies of iPSC therapiesSummaryHere, we describe the humanized model created using non-fetal human sources, cryopreserved and umbilical cord blood hematopoietic stem cells (HSCs). Conventional models are by engrafting HSCs into immunocompromised mice. These harbor functional T that have matured in...
Highlights•A 3-mm-diameter graft is developed using PSC-derived arterial endothelial cells•MHC-WT grafts maintain 100% patency for 6 months in an allogeneic rhesus model•The endothelium repopulated with host cells, ensuring the long-term patencySummaryAutologous vascular grafts, only clinically approved option small-diameter (<6 mm) revascularizations, require invasive harvesting and have limited availability variable quality. To address these challenges, we develop a artery by cells (AECs)...
Abstract Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) exhibit a fetal phenotype that limits in vitro and therapeutic applications. Strategies to promote cardiomyocyte maturation have focused interventions on differentiated hPSC-CMs, but this study tests priming of early cardiac progenitor cells (CPCs) with polyinosinic-polycytidylic acid (pIC) accelerate maturation. CPCs were from hPSCs using monolayer differentiation protocol defined small molecule Wnt temporal modulation,...
Study of stem cells may reveal promising treatment for diseases. The fate and function transplanted remain poorly defined. Recent studies demonstrate that reporter genes can monitor real-time survival in living subjects. We examined the effects a novel versatile triple fusion (TF) gene construction on embryonic (ES) cell by proteomic analysis. Murine ES were stably transduced with self-inactivating lentiviral vector containing fluorescence (firefly luciferase; Fluc), bioluminescence...
Contractile to synthetic phenotypic switching of smooth muscle cells (SMCs) contributes stenosis in vascular disease and transplants. To generate more contractile SMCs, we performed a high-throughput differentiation screen using MYH11-NLuc-tdTomato human embryonic stem cell reporter line. We identified RepSox as factor that promotes MYH11-positive by promoting NOTCH signaling. induces SMCs exhibit phenotype than generated PDGF-BB TGF-β1, two factors previously used for SMC but which also...
Hypoimmune gene edited human pluripotent stem cells (hPSCs) are a promising platform for developing reparative cellular therapies that evade immune rejection. Existing first-generation hypoimmune strategies have used CRISPR/Cas9 editing to modulate genes associated with adaptive (e.g., T cell) responses, but largely not addressed the innate monocytes, neutrophils) mediate inflammation and rejection processes occurring early after graft transplantation. We identified adhesion molecule ICAM-1...
T helper 17 (Th17)–dependent autoimmune responses can develop after heart or lung transplantation and are associated with fibro-obliterative forms of chronic rejection; however, the specific self-antigens involved typically different from those disease. To investigate basis these responses, we investigated whether removal regulatory cells blockade function reveals a similar autoantigen bias. We found that Th17 for collagen type V (Col V), kα1-tubulin, vimentin were present in healthy adult...
Abstract Translation of wound healing research is limited by the lack an appropriate animal model, due to anatomic and differences in animals humans. Here, we characterize grafted, full‐thickness human skin vivo model healing. Full‐thickness skin, obtained from reconstructive operations, was grafted onto dorsal flank NOD.Cg‐ Kit W41J Tyr + Prkdc scid Il2rg tm1Wjl /ThomJ mice. The xenografts were harvested 1 12 weeks after grafting, histologic analyses completed for viability,...
Abstract Genetically diverse simian arteriviruses (simarteriviruses) naturally infect geographically and phylogenetically monkeys, cross-species transmission emergence are of considerable concern. Characterization most simarteriviruses beyond sequence analysis has not been possible because the viruses fail to propagate in laboratory. We attempted isolate 4 simarteriviruses, Kibale red colobus virus 1, Pebjah virus, hemorrhagic fever Southwest baboon by inoculating an immortalized grivet cell...
Background Arterial bypass and interposition grafts are used routinely across multiple surgical subspecialties. Current options include both autologous synthetic materials; however, each graft presents specific limitations. Engineering artificial small-diameter arteries with vascular cells derived from induced pluripotent stem could provide a useful therapeutic solution. Banking rare individuals who homozygous for human leukocyte antigen alleles has been proposed as strategy to facilitate...
Nonhuman primates (NHPs) represent one of the most important models for preclinical studies novel biomedical interventions. In contrast with small animal models, however, widespread utilization NHPs is restricted by cost, logistics, and availability. Therefore, we sought to develop a translational primatized mouse model, akin humanized mouse, allow high-throughput in vivo experimentation leveraged inform large immunology-based studies. We found that adult rhesus macaque mobilized blood (AMb)...
Receptor-interacting protein kinase 1 (RIPK1) is a threonine/serine that serves as critical regulator of immune re-sponses and cell death pathways, functioning through both its catalytic activity non-catalytic scaffold function. The function RIPK1 contributes to intrinsic extrinsic resistance checkpoint blockades (ICBs), making it compelling therapeutic target for enhancing cancer immunotherapy. Recent studies have highlighted RIPK1’s potential key modulator improving the efficacy...