Objectives. The objective of this study was to investigate the therapeutic effect of
Introduction: The existence of circulating skeletal stem cells in the peripheral blood from different species including adult mouse and human has been found and documented. The circulating skeletal stem cells may provide a new source of stem cells that may be used for bone regeneration and tissue engineering applications. The aim of this study was to investigate the existence of circulating osteogenic stem cells in the rat peripheral blood, and to compare their osteogenic potentials with bone marrow mesenchymal stem cells (BMMSCs). Methods: Whole blood from twelve female 3-month old SD rats was harvested by cardiac puncture and bone marrows were also collected. Mononuclear cells from both bone marrow and peripheral blood (PBMNCs) were isolated by Lymphoprep density gradient centrifugation method, and plated at a density of 300000 to 400000/cm2 in flasks with á-MEM medium and 15% FCS. The colony forming efficiency (CFE) was calculated after 10–14 days culture. The osteogenic, adipogenic, and chondrogenic differentiation potential of both BMMSCs and
Objectives. In order to screen the altered gene expression profile in
Aims. To investigate the correlations among cytokines and regulatory T cells (T-regs) in ankylosing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-α (TNF-α) treatment. Methods. We included 72 AS patients with detailed medical records, disease activity score (Bath Ankylosing Spondylitis Disease Activity Index), functional index (Bath Ankylosing Spondylitis Functional Index), and laboratory data (interleukin (IL)-2, IL-4, IL-10, TNF-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, ESR, and CRP). Their
Objectives. The molecular mechanism of rheumatoid arthritis (RA) remains elusive. We conducted a protein-protein interaction network-based integrative analysis of genome-wide association studies (GWAS) and gene expression profiles of RA. Methods. We first performed a dense search of RA-associated gene modules by integrating a large GWAS meta-analysis dataset (containing 5539 RA patients and 20 169 healthy controls), protein interaction network and gene expression profiles of RA synovium and
Chronic Achilles tendinopathy is characterised by sub-acute inflammation with pro-inflammatory type 1 macrophages (M1), tissue degeneration and consequent partial or total tendon injury. Control of the inflammatory response and M1-to-M2 macrophage polarisation can favour tendon healing both directly and indirectly, by allowing for the regenerative process driven by local mesenchymal stem cells. Ten patients (3 females and 7 males aged between 32 and 71 years old) with partial Achilles tendon injury were treated with injections of autologous
Aims. Early evidence has emerged suggesting that ceramic-on-ceramic
articulations induce a different tissue reaction to ceramic-on-polyethylene
and metal-on-metal bearings. Therefore, the aim of this study was
to investigate the tissue reaction and cellular response to ceramic
total hip arthroplasty (THA) materials in vitro,
as well as the tissue reaction in capsular tissue after revision
surgery of ceramic-on-ceramic THAs. Patients and Methods. We investigated tissue collected at revision surgery from nine
ceramic-on-ceramic articulations. we compared our findings with
tissue obtained from five metal-on-metal THA revisions, four ceramic-on-polyethylene
THAs, and four primary osteoarthritis synovial membranes. The latter
were analyzed to assess the amount of tissue fibrosis that might
have been present at the time of implantation to enable evaluation,
in relation to implantation time, of any subsequent response in
the tissues. Results. There was a significant increase in tissue fibrosis with implantation
time for all implant types tested. Interestingly, the tissue fibrosis
in ceramic-on-ceramic THAs was significantly increased compared
with metal-on-metal and ceramic-on-polyethylene. Additionally, we
found ceramic wear particles in the periprosthetic tissue of ceramic implants.
Fibroblasts responded with expression of cytokines when cultured
on alumina-toughened zirconia (ATZ) and zirconia-toughened alumina
(ZTA) ceramic surfaces. This response was more pronounced on ATZ
ceramics compared with ZTA ceramics. The same inflammatory response
was observed with
Bone tissue engineering attempts at substituting critical size bone defects with scaffolds that can be primed with osteogenic cells, usually mesenchymal stem cells (MSC) from the bone marrow. Although overlooked, peripheral blood is a valuable source of MSC and circulating osteoprogenitors (COP), bearing a significant regenerative potential, and peripheral blood is easier to access than bone marrow. We thus studied osteodifferentiation of
Since 2010, there has been a sharp decline in the use of metal-on-metal joint replacement devices due to adverse responses associated with the release of metal wear particles and ions in patients. Surface engineered coatings offer an innovative solution to this problem by covering metal implant surfaces with biocompatible and wear resistant materials. The present study tests the hypothesis whether surface engineered coatings can reduce the overall biological impact of a device by investigating recently introduced silicon nitride coatings for joint replacements. Biological responses of
Currently, different techniques to evaluate the biocompatibility of orthopaedic materials, including two-dimensional (2D) cell culture for metal/ceramic wear debris and floating 2D surfaces or three-dimensional (3D) agarose gels for UHMWPE wear debris, are used. Moreover, cell culture systems evaluate the biological responses of cells to a biomaterial as the combined effect of both particles and ions. We have developed a novel cell culture system suitable for testing the all three type of particles and ions, separately. The method was tested by evaluating the biological responses of human
Aims: Compelling evidences suggest that increased production of osteoclastogenic cytokines by activated T cells plays a relevant role in the bone loss induced by estrogen (E) deficiency in the mouse. However, little information is available on the role of T cells in post-menopausal bone loss in humans. Methods: To investigate this issue we have assessed the production of cytokines involved in osteoclasts (OCs) formation (RANKL, TNFα and OPG), in vitro Ocs formation in pre and postmenopausal women, the latter with or without osteoporosis. We also evaluate OC precursors in peripheral blood and the ability of
One possible mechanism by which metal-on-metal hip resurfacing (MOMHR) may be associated with prosthesis loosening, periprosthetic fracture, and femoral neck narrowing is through an increase in bone resorption by osteoclast cells. Whilst it is known that metal ions such as cobalt (Co) and chromium (Cr) ions (that are elevated locally and systemically after MOMHR), may affect osteoblast and macrophage activity in-vitro, little is known about the effect of these ions on osteoclasts. We examined whether these ions have an adverse effect on human peripheral blood derived osteoclasts at levels that are clinically relevant after MOMHR.
Osteomyelitis commonly causes bone destruction and is most frequently due to infection by Staphylococcus aureus. S. aureus is known to secrete a number of surface-associated proteins which are extremely potent stimulators of bone resorption in the mouse calvarial assay system. The precise cellular and humoral mechanisms whereby this stimulatory effect is mediated, in particular whether osteoclast formation or activity is directly promoted by these factors, have not been determined by this study. Surface-associated material (SAM)(0.001ug/ml)obtained from 24 hour cultures of S. aureus was added to cultures of mouse and human osteoclast precursors (RAW 264.7 cells and human
Background: Circulating endothelial precursor cells (CEPS) are thought to play a role in postnatal angiogenesis. We investigated the angiogenic stress of musculoskeletal trauma on CEP kinetics in trauma patients and their bone marrow progenitor populations in a murine model. Methods:
Introduction. There are several potential biological mechanisms that may influence aseptic implant failure including excessive innate and adaptive immune responses to implant debris. We investigated the hypothesis that patients with painful total joint replacements will exhibit elevated levels of metal reactivity and inflammatory markers compared to patients with well-performing TJA. We evaluated this hypothesis by testing for metal hypersensitivity using in vitro LTT assay and analyzing serum levels of selected inflammatory markers. Methods. Subject Groups: Blinded de-identified data from patients with TJR referred for metal hypersensitivity testing using a lymphocyte transformation test (LTT) and serum markers of inflammation using Luminex Multi-Analyte Assay was approved by Rush University IRB and retrospectively reviewed. None of the patients had radiographically identifiable osteolysis. Two groups of TJA patients were tested: Group 1: Well-functioning implant (<3 yrs. post-op), with no self-reported pain, i.e. <1 on 0–10 VAS scale (n=8) and Group 2: Painful TJR (<3 yrs. post-op), with self-determined pain of >8 on a 0–10 VAS scale at the time of blood draw (n=25). Metal-LTT:
Introduction and aim: We have previously shown suppressed levels of CD8+ T lymphocytes in patients with metal-on-metal (MOM) hip resurfacing compared to patients with metal on polyethylene hip replacements. Functional assessment of T lymphocytes may help to determine the importance of this CD8+ reduction following hip resurfacing. Method: We isolated
Cytological analysis of material aspirated from the effusion which occasionally develops around a polyglycolic acid (PGA) osteosynthesis implant showed a predominance of inflammatory monocytes and in particular lymphocytes. In order to discover whether PGA implants are immunologically inert, density gradient-isolated
We developed a 3D vascularized bone remodeling model embedding human osteoblast and osteoclast precursors and endothelial cells in a mineralized matrix. All the cells included in the model exerted their function, resulting in a vascularized system undergoing mineralized matrix remodeling. Bone remodeling is a dynamic process relying on the balance between the activity of osteoblasts and osteoclasts which are responsible for bone formation and resorption, respectively. This process is also characterized by a tight coupling between osteogenesis and angiogenesis, indicating the existence of a complex cross-talk between endothelial cells and bone cells. We have recently developed microscale in vitro hydrogel-based models, namely the 3D MiniTissue models, to obtain bone-mimicking microenvironments including a 3D microvascular network formed by endothelial cell self-assembly [1–2]. Here, we generated a vascularized 3D MiniTissue bone remodeling model through the coculture of primary human cells in a 3D collagen/fibrin (Col/Fib) matrix enriched with CaP nanoparticles (CaPn) to mimic bone mineralized matrix. Human umbilical vein endothelial cells (HUVECs), bone marrow mesenchymal stem cells (BMSCs), osteoblast (OBs) and osteoclast (OCs) precursors were cocultured in plain and CaPn-enriched Col/Fib according to the following experimental conditions: a) HUVECs-BMSCs; b) OBs-OCs; c) HUVECs-BMSCs-OBs-OCs. Undifferentiated BMSCs were used to support HUVECs in microvascular network formation. BMSCs and
Introduction: Immune responses in patients susceptible to aseptic loosening may differ to those without this susceptibility. We compared stimulated cytokine mRNA and protein expression in
Aims: Circulating endothelial precursor cells (CEPs) are thought to play a role in angiogenesis. We investigated the angiogenic stress of musculoskeletal trauma on CEP kinetics in trauma patients and their bone marrow progenitor populations in a murine model. Methods: