- Mesenchymal stem cell research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Tissue Engineering and Regenerative Medicine
- Cancer Cells and Metastasis
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immune cells in cancer
- Hematopoietic Stem Cell Transplantation
- Virus-based gene therapy research
- Cancer Research and Treatments
- Electrospun Nanofibers in Biomedical Applications
- RNA Interference and Gene Delivery
- Synthesis and Biological Evaluation
- Angiogenesis and VEGF in Cancer
- Extracellular vesicles in disease
- Biomedical Ethics and Regulation
- Pluripotent Stem Cells Research
- Salivary Gland Disorders and Functions
- Phagocytosis and Immune Regulation
- Monoclonal and Polyclonal Antibodies Research
- Chemokine receptors and signaling
- Neonatal Respiratory Health Research
- Cytokine Signaling Pathways and Interactions
- Viral Infectious Diseases and Gene Expression in Insects
University of Wisconsin–Madison
2016-2025
University of Wisconsin Carbone Cancer Center
2016-2025
UW Health University Hospital
2021-2025
University of Wisconsin System
2019-2024
Georgetown University
2023
MedStar Georgetown University Hospital
2023
Madison Group (United States)
2022-2023
Stemcell Technologies
2020-2022
Leiden University Medical Center
2020
Emory University
2010-2017
Clinical trials testing the use of either autologous or allogeneic human bone marrow-derived mesenchymal stromal cells (MSC) as a cell-based pharmaceutical for suppression autoimmune and alloimmune ailments are underway. Reported results from completed vary in effectiveness within between studies without any clear mechanistic explanation. We propose that these discrepancies may arise intrinsic variability immunosuppressive potential each MSC donor source. Here, we demonstrate tumor necrosis...
Rationale: Bronchopulmonary dysplasia (BPD) and emphysema are characterized by arrested alveolar development or loss of alveoli; both significant global health problems currently lack effective therapy. Bone marrow–derived mesenchymal stem cells (BMSCs) prevent adult lung injury, but their therapeutic potential in neonatal disease is unknown.Objectives: We hypothesized that intratracheal delivery BMSCs would destruction experimental BPD.Methods: In vitro, BMSC differentiation migration were...
Abstract The administration of ex vivo culture-expanded mesenchymal stromal cells (MSCs) has been shown to reverse symptomatic neuroinflammation observed in experimental autoimmune encephalomyelitis (EAE). mechanism by which this therapeutic effect occurs remains unknown. In an effort decipher MSC mode action, we found that conditioned medium inhibits EAE-derived CD4 T cell activation suppressing STAT3 phosphorylation via MSC-derived CCL2. Further analysis demonstrates the is dependent on...
Bone marrow-derived mesenchymal stromal cells (MSC) possess an immune plasticity manifested by either immunosuppressive or, when activated with IFN-gamma, APC phenotype. Herein, TLR expression MSC and their regulatory role were investigated. We observed that human macrophages expressed TLR3 TLR4 at comparable levels TLR-mediated activation of resulted in the production inflammatory mediators such as IL-1beta, IL-6, IL-8/CXCL8, CCL5. IFN-alpha or IFN-gamma priming up-regulated these IFNB,...
Human bone marrow-derived mesenchymal stromal cells (MSCs) inhibit proliferation of activated T cells, and IFN-γ plays an important role in this process. This IFN-γ-licensed veto property is IDO-dependent. To further decipher the mechanistic underpinnings MSC function on we investigated effect MSCs cell effector as assayed by cytokine secretion cells. Although proliferation, only significantly Th1 (IFN-γ, TNF-α, IL-2) production Additionally, degranulation well single, double, triple...
Recent evidence indicates that bone-marrow-derived stromal cells (MSCs) have a histology coherent with endothelial may enable them to contribute tumor angiogenesis through yet undefined mechanisms. In this work, we investigated the angiogenic properties of murine MSCs involved in extracellular matrix degradation and neovascularization could take place hypoxic environment such as encountered masses. were cultured normoxia (95% air 5% CO2) or hypoxia (1% oxygen, CO2, 94% nitrogen). We found...
Abstract Mesenchymal stromal cells (MSC) possess immunosuppressive properties, yet when treated with IFN-γ they acquire APC functions. To gain insight into MSC immune plasticity, we explored signaling pathways induced by required for MHC class II (MHC II)-dependent Ag presentation. IFN-γ-induced expression in mouse was enhanced high cell density or serum deprivation and suppressed TGF-β. This process regulated the activity of type IV CIITA promoter independently STAT1 activation induction...
The mechanism by which gap junction proteins, connexins, act as potent tumor suppressors remains poorly understood. In this study human breast cells were found to exhibit diverse phenotypes including (a) undetectable Cx43 and no intercellular communication (HBL100); (b) low levels of sparse (MDA-MB-231); (c) significant moderate (Hs578T). Although retroviral delivery Cx26 cDNAs MDA-MB-231 did not achieve an expected substantial rescue communication, overexpression connexin genes result in a...
The modification of glutamic acid residues to gamma-carboxyglutamic (Gla) is a post-translational catalyzed by the vitamin K-dependent enzyme gamma-glutamylcarboxylase. Despite ubiquitous expression gamma-carboxylation machinery in mammalian tissues, only 12 Gla-containing proteins have so far been identified humans. Because bone tissue second most abundant source after liver, we sought identify Gla secreted marrow-derived mesenchymal stromal cells (MSCs). We used proteomics approach screen...
Assays that can characterize MSC immune potency need to be identified for use in advanced clinical trials. MSCs possess a number of putative regenerative and immunomodulatory properties, an assay matrix approach may best capture involved effector pathways. We have tested two systems measure the derived from human subjects: secretome analysis quantitative RNA-based array genes specific homing properties MSCs. Secretome unique cytokine signature is upregulated by or downregulated responder...