showing 30 related works from this author
Progress of Phototherapy Applications in the Treatment of Bone Cancer
2021
Bone cancer including primary bone cancer and metastatic bone cancer, remains a challenge claiming millions of lives and affecting the life quality of survivors. Conventional treatments of bone cancer include wide surgical resection, radiotherapy, and chemotherapy. However, some bone cancer cells may remain or recur in the local area after resection, some are highly resistant to chemotherapy, and some are insensitive to radiotherapy. Phototherapy (PT) including photodynamic therapy (PDT) and photothermal therapy (PTT), is a clinically approved, minimally invasive, and highly selective treatment, and has been widely reported for cancer therapy. Under the irradiation of light of a specific wa…
Calf Blood Compound (CFC) and Homeopathic Drug Induce Differentiation of Primary Human Skeletal Muscle Cells.
2019
AbstractThe use of injections to treat structural muscle injuries is controversially discussed. In our controlled in vitro study, we investigated the biological impact of Actovegin and Traumeel alone and in combination on primary human skeletal muscle cells. Cells were characterized by immunofluorescence staining for myogenic factor 5 (Myf5) and MyoD, and cultured with or without Actovegin and / or Traumeel. The effects of these agents were assayed by cell viability and gene expression of the specific markers MyoD, Myf5, neural adhesion molecule (NCAM), and CD31. Myotube formation was determined by myosin staining. Neither Actovegin nor Traumeel showed toxic effects or influenced cell viabi…
Cytokine Interferon-γ suppresses the function of capsule myofibroblasts and induces cell apoptosis
2017
Myofibroblasts (MFs), a contractile subset of fibroblasts, play a pivotal role in physiological wound healing and in the development of many fibroconnective disorders. The complex cytokine network regulating the function of MFs in joint stiffness is still poorly understood. In this in vitro study, we investigated the effect of the cytokine Interferon-gamma (IFN-γ) on MFs isolated from human joint capsules. MFs were cultivated either in the presence of increasing concentrations of IFN-γ alone or in combination with IFN-γ neutralizing antibodies. Cell viability, cytotoxicity, apoptosis, and mRNA gene expression of the MF markers alpha-smooth muscle actin (α-SMA) and collagen type I were analy…
Influence of different calcium phosphate ceramics on growth and differentiation of cells in osteoblast-endothelial co-cultures
2016
Strategies for improvement of angiogenesis and vasculogenesis using different cells and materials are paramount aims in the field of bone tissue engineering. Thereby, the interaction between different cell types and scaffold materials is crucial for growth, differentiation, and long-term outcomes of tissue-engineered constructs. In this study, we evaluated the interaction of osteoblasts and endothelial cells in three-dimensional tissue-engineered constructs using beta tricalciumphosphate (β-TCP, [s-Ca3 (PO4 )2 ]) and calcium-deficient hydroxyapatite (CDHA, [Ca9 (PO4 )5 (HPO4 )OH]) ceramics as scaffolds. We focused on initial cell organization, cell proliferation, and differential expression…
Functional cysteine-less subunits of the transporter associated with antigen processing (TAP1 and TAP2) by de novo gene assembly
2002
AbstractWithin the adaptive immune system the transporter associated with antigen processing (TAP) plays a pivotal role in loading of peptides onto major histocompatibility (MHC) class I molecules. As a central tool to investigate the structure and function of the TAP complex, we created cysteine-less human TAP subunits by de novo gene synthesis, replacing all 19 cysteines in TAP1 and TAP2. After expression in TAP-deficient human fibroblasts, cysteine-less TAP1 and TAP2 are functional with respect to adenosine triphosphate (ATP)-dependent peptide transport and inhibition by ICP47 from herpes simplex virus. Cysteine-less TAP1 and TAP2 restore maturation and intracellular trafficking of MHC c…
Analysis of the structural integrity of the TAP2 gene in renal cell carcinoma.
2003
The transporter associated with antigen processing (TAP) gene products is involved in the processing of endogenous peptides that bind to MHC class I molecules. Mutations and/or polymorphism within these genes could alter the efficacy of the immune response which might be relevant for the development of autoimmune diseases and cancer. In this study we examined both the structural integrity and the polymorphism of TAP2 in renal cell carcinoma lesions by sequencing TAP2 in renal cell carcinoma lesions and autologous normal kidney epithelium. TAP2 sequence analysis of 31 renal cell carcinoma lesions, one oncocytoma and respective autologous normal kidney epithelium revealed no mutation in the T…
Exposure to radial extracorporeal shockwaves induces muscle regeneration after muscle injury in a surgical rat model
2019
The leading cause of training interruption in sport is a muscle injury, for which the standard treatment is nonsteroidal anti-inflammatory drugs (NSAIDs). To find alternative treatments, we investigated whether the radial extracorporeal shockwave application (rESWT) could stimulate muscle regeneration. A lesion with complete rupture (grade III muscle tear) was set in the musculus rectus femoris of 12-week-old Wistar rats, and the NSAID diclofenac, rESWT, or a combined therapy were applied on day 0, 3, and 5 directly following the surgery. Rats were euthanized at 2, 4, and 7 days after surgery and the area of muscle lesion was excised for histological and gene expression analysis to determin…
Cell viability, osteoblast differentiation, and gene expression are altered in human osteoblasts from hypertrophic fracture non-unions
2007
Recent studies have provided evidence that the number and proliferation capacity of bone marrow-derived mesenchymal stem cells, as well as the number of osteoprogenitor cells are reduced in patients with fracture non-unions. For fracture non-unions that do not heal after appropriate surgical intervention, the question arises as to what extent systemic cellular dysfunctions should be considered as being pathogenetic factors. For this purpose, we have examined the hypothesis that the cell function of osteoblasts isolated from patients with fracture non-unions may differ from those of normal control individuals in an identical and controlled in vitro situation. We analyzed the osteoblast cell …
The Transporter Associated With Antigen Processing (TAP): Structural Integrity, Expression, Function, and Its Clinical Relevance
2001
BACKGROUND: The transporter associated with antigen processing (TAP), a member of the family of ABC transporters, plays a crucial role in the processing and presentation of the major histocompatibility complex (MHC) class I restricted antigens. TAP transports peptides from the cytosol into the endoplasmic reticulum, thereby selecting peptides matching in length and sequence to respective MHC class I molecules. Upon loading on MHC class I molecules, the trimeric MHC class I/beta2-microglobulin/ peptide complex is then transported to the cell surface and presented to CD8+ cytotoxic T cells. Abnormalities in MHC class I surface expression have been found in a number of different malignancies, …
High frequency of a non-functional TAP1/LMP2 promoter polymorphism in human tumors
2002
The Tap1 and Tap2 genes encoding for a heterodimeric peptide transporter play a key role in antigen processing and presentation. The TAP complex mediates the transport of peptides generated by the IFN-gamma-inducible proteasome subunits LMP2, 7 and 10 from the cytosol into the endoplasmic reticulum (ER), where they bind to MHC class I molecules. In contrast to the frequent polymorphisms within the rat Tap genes which exert functional differences, polymorphic regions within the human Tap genes have been demonstrated, but not systematically analyzed in terms of their functional significance. Both the Tap1 and Lmp2 genes are transcribed from a bidirectional intergenic promoter which is regulat…
Mechanical characterization of rose bengal and green light crosslinked collagen scaffolds for regenerative medicine
2021
Abstract Collagen is one of the most important biomaterials for tissue engineering approaches. Despite its excellent biocompatibility, it shows the non-negligible disadvantage of poor mechanical stability. Photochemical crosslinking with rose bengal and green light (RGX) is an appropriate method to improve this property. The development of collagen laminates is helpful for further adjustment of the mechanical properties as well as the controlled release of incorporated substances. In this study, we investigate the impact of crosslinking and layering of two different collagen scaffolds on the swelling behavior and mechanical behavior in micro tensile tests to obtain information on its wearin…
<p>Effects of losartan and atorvastatin on the development of early posttraumatic joint stiffness in a rat model</p>
2019
Background After a trauma, exuberant tissue healing with fibrosis of the joint capsule can lead to posttraumatic joint stiffness (PTJS). Losartan and atorvastatin have both shown their antifibrotic effects in different organ systems. Objective The purpose of this study was the evaluation of the influence of losartan and atorvastatin on the early development of joint contracture. In addition to joint angles, the change in myofibroblast numbers and the distribution of bone sialoprotein (BSP) were assessed. Study design and methods In this randomized and blinded experimental study with 24 rats, losartan and atorvastatin were compared to a placebo. After an initial joint injury, rat knees were …
Dexamethasone Inhibits the Pro-Angiogenic Potential of Primary Human Myoblasts
2021
Tissue regeneration depends on the complex processes of angiogenesis, inflammation and wound healing. Regarding muscle tissue, glucocorticoids (GCs) inhibit pro-inflammatory signalling and angiogenesis and lead to muscle atrophy. Our hypothesis is that the synthetic GC dexamethasone (dex) impairs angiogenesis leading to muscle atrophy or inhibited muscle regeneration. Therefore, this study aims to elucidate the effect of dexamethasone on HUVECs under different conditions in mono- and co-culture with myoblasts to evaluate growth behavior and dex impact with regard to muscle atrophy and muscle regeneration. Viability assays, qPCR, immunofluorescence as well as ELISAs were performed on HUVECs,…
Photocrosslinkable polysaccharide hydrogel composites based on dextran or pullulan-amylose blends with cytokines for a human co-culture model of huma…
2016
Although a large body of research has been devoted to biomaterial development for bone tissue engineering and related medical disciplines in the last few years, novel and optimized materials especially for bone fractures of critical sizes demand continued development. In this respect, polysaccharide-based hydrogels demonstrate beneficial properties and fulfill the main requirements for a bone tissue scaffold as they are hydrophilic, biocompatible, and biodegradable. The aim of the present study was the development of a natural polysaccharide-based scaffold material that can integrate with the host tissue and support bone regeneration. For this purpose, we prepared and investigated two polym…
CD34+cells seeded in collagen scaffolds promote bone formation in a mouse calvarial defect model
2017
Bone tissue engineering (BTE) holds promise for managing the clinical problem of large bone defects. However, clinical adoption of BTE is limited due to limited vascularization of constructs, which could be circumvented by pre-cultivation of osteogenic and endothelial derived cells in natural-based polymer scaffolds. However, until now not many studies compared the effect of mono- and cocultures pre-seeded in collagen before implantation. We utilized a mouse calvarial defect model and compared five groups of collagen scaffolds: a negative control of a collagen scaffold alone, a positive control treated with BMP-7, monocultures of either human osteoblasts (hOBs) or CD34+ cells, and a cocultu…
Toxic Effect of Vancomycin on Viability and Functionality of Different Cells Involved in Tissue Regeneration
2020
To prevent infections local delivery of antibiotics is a useful tool. Especially in bone fractures, vancomycin impregnated bone cements are often used allowing high concentrations of antibiotics at the infection side without high serum concentrations. However, besides potential pathogens, cells involved in tissue regeneration may also be affected by the drug. We investigated the effect of vancomycin on the viability and functionality on osteoblasts, endothelial cells, fibroblasts and skeletal muscle cells. Our results show that the viability of all cells analyzed was reduced by vancomycin and that the observed effects were time and concentration dependent. The most pronounced toxic effect w…
Die intramuskuläreInjektion von Actovegin und Traumeel beschleunigt die Muskelregeneration in vivo
2020
Identification of sequences in the human peptide transporter subunit TAP1 required for transporter associated with antigen processing (TAP) function
2001
The heterodimeric peptide transporter associated with antigen processing (TAP) consisting of the subunits TAP1 and TAP2 mediates the transport of cytosolic peptides into the lumen of the endoplasmic reticulum (ER). In order to accurately define domains required for peptide transporter function, a molecular approach based on the construction of a panel of human TAP1 mutants and their expression in TAP1(-/-) cells was employed. The characteristics and biological activity of the various TAP1 mutants were determined, and compared to that of wild-type TAP1 and TAP1(-/-) control cells. All mutant TAP1 proteins were localized in the ER and were capable of forming complexes with the TAP2 subunit. H…
Impaired Transporter Associated with Antigen Processing (TAP) Function Attributable to a Single Amino Acid Alteration in the Peptide TAP Subunit TAP1
2003
Abstract The heterodimeric peptide transporter TAP belongs to the ABC transporter family. Sequence comparisons with the P-glycoprotein and cystic fibrosis transmembrane conductance regulator and the functional properties of selective amino acids in these ABC transporters postulated that the glutamic acid at position 263 and the phenylalanine at position 265 of the TAP1 subunit could affect peptide transporter function. To define the role of both amino acids, TAP1 mutants containing a deletion or a substitution to alanine at position 263 or 265 were generated and stably expressed in murine and human TAP1−/− cells. The different TAP1 mutants were characterized in terms of expression and funct…
Molecular mechanisms of HLA class I antigen abnormalities following viral infection and transformation.
2005
In humans as in other animal species, CD8+ cytotoxic T lymphocytes (CTLs) play an important if not the major role in controlling virus-infected and malignant cell growth. The interactions between CD8+ T cells and target cells are mediated by human leukocyte antigen (HLA) class I antigens loaded with viral and tumor antigen-derived peptides along with costimulatory receptor/ligand stimuli. Thus, to escape from CD8+ T-cell recognition and destruction, viruses and tumor cells have developed strategies to inhibit the expression and/or function of HLA class I antigens. In contrast, cells with downregulated MHC class I surface expression can be recognized by NK cells, although NK cell-mediated ly…
3D Bioprinting for Vascularized Tissue-Engineered Bone Fabrication
2020
Vascularization in bone tissues is essential for the distribution of nutrients and oxygen, as well as the removal of waste products. Fabrication of tissue-engineered bone constructs with functional vascular networks has great potential for biomimicking nature bone tissue in vitro and enhancing bone regeneration in vivo. Over the past decades, many approaches have been applied to fabricate biomimetic vascularized tissue-engineered bone constructs. However, traditional tissue-engineered methods based on seeding cells into scaffolds are unable to control the spatial architecture and the encapsulated cell distribution precisely, which posed a significant challenge in constructing complex vascul…
Major Histocompatibility Complex Modulation and Loss
2002
Photocrosslinked Dextran-Based Hydrogels as Carrier System for the Cells and Cytokines Induce Bone Regeneration in Critical Size Defects in Mice
2018
Modified biomaterials have for years been the focus of research into establishing new bone substitutes. In our preceding in vitro study employing different cell cultures, we developed chemically and mechanically characterized hydrogels based on photocrosslinkable dextran derivatives and demonstrated their cytocompatibility and their beneficial effects on the proliferation of osteoblasts and endothelial cells. In the present in vivo study, we investigate photocrosslinked dextran-based hydrogels in critical size defects in mice to evaluate their potential as carrier systems for cells or for a specific angiogenesis enhancing cytokine to induce bone formation. We could demonstrate that, with op…
Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma.
2001
In cervical carcinomas abnormalities in the MHC class I surface expression are a frequent event, which are often associated with the deficient expression of the peptide transporter subunit TAP1 thereby resulting in impaired T cell response. In order to understand the role of other components of the MHC class I antigen processing machinery (APM) in the immune escape, 16 surgically removed primary cervical carcinoma lesions were analyzed for their mRNA expression of the heterodimeric peptide transporter TAP, the constitutive and interferon (IFN)-gamma inducible proteasome subunits and their activators PA28alpha/beta, various chaperones as well as MHC class I antigens. High expression levels o…
Effect of bone sialoprotein coated three-dimensional printed calcium phosphate scaffolds on primary human osteoblasts
2018
The combination of the two techniques of rapid prototyping 3D-plotting and bioactive surface functionalization is presented, with emphasis on the in vitro effect of Bone Sialoprotein (BSP) on primary human osteoblasts (hOBs). Our primary objective was to demonstrate the BSP influence on the expression of distinctive osteoblast markers in hOBs. Secondary objectives included examinations of the scaffolds' surface and the stability of BSP-coating as well as investigations of cell viability and proliferation. 3D-plotted calcium phosphate cement (CPC) scaffolds were coated with BSP via physisorption. hOBs were seeded on the coated scaffolds, followed by cell viability measurements, gene expressi…
The effect of the pro-inflammatory cytokine tumor necrosis factor-alpha on human joint capsule myofibroblasts.
2009
Introduction Previous studies have shown that the number of myoblastically differentiated fibroblasts known as myofibroblasts (MFs) is significantly increased in stiff joint capsules, indicating their crucial role in the pathogenesis of post-traumatic joint stiffness. Although the mode of MFs' function has been well defined for different diseases associated with tissue fibrosis, the underlying mechanisms of their regulation in the pathogenesis of post-traumatic joint capsule contracture are largely unknown. Methods In this study, we examined the impact of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) on cellular functions of human joint capsule MFs. MFs were challenged w…
The effect of human osteoblasts on proliferation and neo-vessel formation of human umbilical vein endothelial cells in a long-term 3D co-culture on p…
2008
Angiogenesis is a key element in early wound healing and is considered important for tissue regeneration and for directing inflammatory cells to the wound site. The improvement of vascularization by implementation of endothelial cells or angiogenic growth factors may represent a key solution for engineering bone constructs of large size. In this study, we describe a long-term culture environment that supports the survival, proliferation, and in vitro vasculogenesis of human umbilical vein endothelial cells (HUVEC). This condition can be achieved in a co-culture model of HUVEC and primary human osteoblasts (hOB) employing polyurethane scaffolds and platelet-rich plasma in a static microenvir…
Photocrosslinkable dextran hydrogel films as substrates for osteoblast and endothelial cell growth
2012
Functional hydrogel films on solid supports are versatile materials with large potential for cell growth and tissue engineering. Here, we report on a modular approach to generate functional hydrogel composite films for endothelial and osteoblast cell co-culture. The polymer network of the parent hydrogel was formed by a dextran derivative (BP-CMD), which contained carboxymethyl (CM) groups for further chemical functionalization and benzophenone (BP) moieties as a photocrosslinkable unit. BP-CMD could be synthesized by three different routes, first with the benzophenone unit attached via an amide bond, or second by an ether bond, or third as an ion pair between the benzophenone ammonium salt…
Influence of the anti-inflammatory cytokine interleukin-4 on human joint capsule myofibroblasts
2016
Post-traumatic joint contracture was reported to be associated with elevated numbers of contractile myofibroblasts (MFs) in the healing capsule. During the physiological healing process, the number of MFs declines; however, in fibroconnective disorders, MFs persist. The manifold interaction of the cytokines regulating the appearance and persistence of MFs in the pathogenesis of joint contracture remains to be elucidated. The objective of our current study was to analyze the impact of the anti-inflammatory cytokine interleukin (IL)-4 on functional behavior of MFs. Cells were isolated from human joint capsule specimens and challenged with three different concentrations of IL-4 with or without…
Extracorporeal shock wave-mediated changes in proliferation, differentiation, and gene expression of human osteoblasts.
2008
The goal of this study was to determine whether cell proliferation, differentiation, and gene expression of primary human osteoblasts (hOB) are influenced by shock wave application (SWA).Osteoblast cultures were isolated from cancellous bone fragments and treated with 500 impulses of energy flux densities of 0.06 mJ/mm, 0.18 mJ/mm, 0.36 mJ/mm, and 0.50 mJ/mm. Twenty-four hours and 96 hours after SWA cell proliferation, alkaline phosphatase activity, and mineralization were analyzed. The global gene expression profiling was determined 96 hours after SWA employing Affymetrix HG-U133A microarrays.After 24 hours, hOB showed a dose-dependent increase in cell proliferation from 68.7% (at 0.06 mJ/…