A5034215419- Multiple Myeloma Research and Treatments
- Bone health and treatments
- Mesenchymal stem cell research
- Bone and Joint Diseases
- Fibroblast Growth Factor Research
- Selenium in Biological Systems
- Computational Drug Discovery Methods
- Kruppel-like factors research
- Radiopharmaceutical Chemistry and Applications
- Redox biology and oxidative stress
- Signaling Pathways in Disease
- Bone Metabolism and Diseases
- Vitamin D Research Studies
- Growth Hormone and Insulin-like Growth Factors
- Cancer, Lipids, and Metabolism
- Medicinal Plant Pharmacodynamics Research
- Muscle Physiology and Disorders
- Alkaline Phosphatase Research Studies
- Medical and Biological Ozone Research
- Lipid metabolism and disorders
- Heterotopic Ossification and Related Conditions
- Peroxisome Proliferator-Activated Receptors
- Chemokine receptors and signaling
- Bone health and osteoporosis research
- Additive Manufacturing and 3D Printing Technologies
University of Würzburg
2008-2025
Klinik König-Ludwig Haus
2025
Orthopedic Center
2009
Universitätsklinikum Würzburg
2007
Bone marrow stromal cells (BMSCs) and other cell populations derived from mesenchymal precursors are developed for cell-based therapeutic strategies undergo cellular stress during ex vivo procedures. Reactive oxygen species (ROS) of environmental origin involved in redox signaling, cumulative damage, senescence, tumor development. Selenium-dependent (glutathione peroxidases [GPxs] thioredoxin reductases [TrxRs]) selenium-independent (superoxide dismutases [SODs] catalase [CAT]) enzyme...
Primary osteoporosis is an age-related disease characterized by imbalance in bone homeostasis. While the resorptive aspect of has been studied intensely, less known about anabolic part syndrome or presumptive deficiencies regeneration. Multipotent mesenchymal stem cells (MSC) are primary source osteogenic In present study we aimed to unravel whether MSC biology directly involved pathophysiology and therefore performed microarray analyses hMSC elderly patients (79-94 years old) suffering from...
The role of serum amyloid A (SAA) proteins, which are ligands for toll-like receptors, was analyzed in human bone marrow-derived mesenchymal stem cells (hMSCs) and their osteogenic offspring with a focus on senescence, differentiation mineralization. In vitro aged hMSC developed senescence-associated secretory phenotype (SASP), resulting enhanced SAA1/2, TLR2/4 proinflammatory cytokine (IL6, IL8, IL1β, CXCL1, CXCL2) expression before entering replicative senescence. Recombinant SAA1 (rhSAA1)...
1,25-dihydroxyvitamin D3 (1,25D3) was reported to induce premature organismal aging in fibroblast growth factor-23 (Fgf23) and klotho deficient mice, which is of main interest as 1,25D3 supplementation its precursor cholecalciferol used basic osteoporosis treatment. We wanted know if able modulate processes on a cellular level human mesenchymal stem cells (hMSC). Effects 100 nM hMSC were analyzed by cell proliferation apoptosis assay, β-galactosidase staining, VDR surface marker...
Abstract During three-dimensional (3D) bioprinting, the integration of living cells into hydrogel matrices results in complex biophysicochemical interactions between viscosity, shear stress, and temperature, critically influencing structural functional integrity resulting constructs. This study delves short-term biological ramifications 3D extrusion printing telomerase-immortalized human mesenchymal stromal (hMSC-TERT) embedded bioinert hydrogels. Pluronic F127 custom-synthesized...
Anti-resorptive bisphosphonates (BP) are used for the treatment of osteoporosis and bone metastases. Clinical studies indicated a benefit in survival tumor relapse subpopulations breast cancer patients receiving zoledronic acid, thus stimulating debate about its anti-tumor activity. Amino-bisphosphonates nM concentrations inhibit farnesyl pyrophosphate synthase leading to accumulation isopentenyl (IPP) ATP/pyrophosphate adduct ApppI, which induces apoptosis osteoclasts. For effects μM needed...
Physical interaction of skeletal precursors with multiple myeloma cells has been shown to suppress their osteogenic potential while favoring tumor-promoting features. Although several transcriptome analyses patient-derived mesenchymal stem have displayed differences compared healthy counterparts, these insufficiently reflect the signatures mediated by tumor cell contact, vary due different methodologies, and lack results in lineage-committed precursors. To determine contact-mediated changes...
e21129 Background: Bisphosphonates (BP) and the RANK-ligand antibody denosumab (D) are used for treatment of bone metastases. Low to high concentrations zoledronic acid (ZA) can induce tumor cell apoptosis in vitro via inhibition mevalonate pathway and/or accumulation ATP analog ApppI. Clinical studies indicate a benefit relapse survival with supportive ER-positive breast cancer using zoledronate (ZA), but molecular mechanisms involved under debate. Methods: MDA-MB-231 MCF-7 cells were...
Multiple myeloma involves early dissemination of malignant plasma cells across the bone marrow; however, initial steps remain unclear. Human marrow-derived mesenchymal stromal (hMSC) stimulate cell expansion (e.g., IL6) and simultaneously retain via chemokines CXCL12) adhesion factors. Hence, we hypothesized that imbalance between division retention drives dissemination. We present an in vitro model using primary hMSCs cocultured with INA-6 cells. Time-lapse microscopy revealed proliferation...
<p>Supplementary Figure 1. Principle and quantification of the V-well adhesion assay fluorescently labeled myeloma cells adapted by Weetall et al. 2001.</p><p>Supplementary 2. Validation image cytometric analysis cell cycle in four INA-6 cultures.</p><p>Supplementary 3. Cell pellets gained from V-Well Adhesion (Fig. 3).</p><p>Supplementary 4. Representative (one independent sample sets as seen Supplementary 3) curve fitting profiles generated Image...
<p>Supplementary Methods</p>
<p>Detachment of INA-6 daughter cells after cell division. <b>A–D,</b> divisions in interaction with confluent hMSCs. Seeding ratio INA-6:MSC = 4:20. <b>A,</b> Three examples dividing generating either two MA, or one MA and nMA as described G. Dashed circles mark mother (white), (blue), first position (green). Scale bar: 20 µm. <b>B,</b> Cell division MSC-adhering (MA) can yield mobile non–MSC-adhering (nMA) cell. <b>C,</b> Frequencies...
<p>Functional analysis of MSC-interacting subpopulations (<b>A</b>–<b>C</b>): Functional enrichment differentially expressed genes (from RNA-seq) using Metascape. <b>A,</b> Gene ontology (GO) cluster gene lists that are unique for MA (left) or nMA (right) INA-6. Circle nodes represent subsets input falling into similar GO term. Node size grows with the number genes. color defines a shared parent Two similarity score > 0.3 linked....
<p>Time-lapse analysis of INA-6 detachment from aggregates and hMSCs. <b>A,</b> Frequency observed that did or not lose cell(s). A total 87 were evaluated per datapoint. <b>B,</b> Example a “disseminating” aggregate growing on fluorescently (PKH26) stained hMSC (from A–D). Dashed green lines are trajectories detached cells. Scale bar = 50 µm. <b>C</b>–<b>E</b>, Quantitative assessment detachments. 45 events Seeding ratio INA-6:MSC 4:1....
<p>Adhesion and ECM genes (shown in <a href="#fig6" target="_blank">Fig. 6A</a>) were filtered by their association with patient survival (<i>P</i>-adj. < 0.01) categorized as continuously downregulated during disease progression</p>
<p>Supplementary Video 4</p>
<p>Supplementary Video 1</p>