Objectives. The objective of this study was to investigate the therapeutic effect of peripheral blood
Objectives. In order to screen the altered gene expression profile in peripheral blood
Post-natal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells migrate, differentiate and incorporate into the nacent endothelium and thereby contribute to physiological and pathological neurovascularisation, has stimulated much interest. Its contribution to neovascularisation of tumours, wound healing and revascularisation associated with ischaemia of skeletal and cardiac muscles is well established. We evaluated the responses of endothelial precursor cells in bone marrow to musculoskeletal trauma in mice. Bone marrow from six C57 Black 6 mice subjected to a standardised, closed fracture of the femur, was analysed for the combined expression of cell-surface markers stem cell antigen 1 (sca-1. +. ) and stem cell factor receptor, CD117 (c-kit. +. ) in order to identify the endothelial precursor cell population. Immunomagnetically-enriched sca-1. +.
Autografts containing bone marrow (BM) are current gold standard in the treatment of critical size bone defects, delayed union and bone nonunion defects. Although reaching unprecedented healing rates in bone reconstruction, the mode of action and cell-cell interactions of bone marrow
Introduction. Homogenous and consistent preparations of mesenchymal stem cells (MSCs) can be acquired by selecting them for integrin α10β1 (integrin a10-MSCs). Safety and efficacy of intra-articular injection of allogeneic integrin a10-MSCs were shown in two post-traumatic osteoarthritis horse studies. The current study investigated immunomodulatory capacities of human integrin a10-MSCs in vitro and their cell fait after intra-articular injection in rabbits. Method. The concentration of produced immunomodulatory factors was measured after licensing integrin a10-MSCs with pro-inflammatory cytokines. Suppression of T-cell proliferation was determined in co-cultures with carboxyfluorescein N-succinimidyl ester (CFSE) labelled human peripheral blood
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 peripheral blood
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 peripheral blood
Introduction. Since 2005, we have performed implantation of bone marrow-derived
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 peripheral blood
Intra-articular injections of human mesenchymal stromal cells (MSCs) and platelet-rich plasma (PRP) have been intensively investigated as therapies for knee osteoarthritis (OA) with positive outcomes. In this work we evaluated weather a combination of the treatments (MSCs + PRP) would be beneficial compared to MSCs alone (MSCs) and standard corticosteroid injection (Control group). Forty seven patients (24 males and 23 females; 53.3 ± 10.7 years old) with radiographic symptomatic knee OA (Dejour grades II–IV) were randomized to receive intra-articular injections of MSCs (n = 16), MSCs + PRP (n = 14) or corticosteroid (n=17). MSCs were obtained after
Mesenchymal stromal cells (MSCs) are widely used in clinical trials for the treatment of many bone defects. Apatite-wollastonite glass ceramic (A-W) is an osteoconductive biomaterial shown to be compatible with MSCs. This is the first study comparing the osteogenic potential of two MSC populations, heterogeneous plastic adherence MSCs (PA-MSCs) and CD271-enriched MSCs (CD271-MSCs), when cultured on A-W 3D scaffold. The paired MSC populations were assessed for their attachment, growth kinetics and ALP activity using confocal or scanning electron microscopy and the quantifications of DNA contents and p-nitrophenyl (pNP) production. While the PA-MSCs and CD271-MSCs had similar expansion and tri-lineage differentiation capacity during standard 2D culture, they showed different proliferation kinetics when seeded on the A-W scaffolds. PA-MSCs displayed a well-spread attachment with more elongated morphology compared to CD271-MSCs, signifying a different level of interaction between the cell populations and the scaffold surface. PA-MSCs also fully integrated into the scaffold surface and showed a stronger propensity for osteogenic differentiation on the A-W scaffold as indicated by higher ALP activity than CD271-MSCs. Furthermore, A-W scaffold seeded uncultured bone marrow
ONFH with large or lateral-located lesion is challenging due to difficulty of regeneration. We introduce novel tissue engineering technique using ex vivo expanded bone marrow stromal cell seeded on calcium metaphosphate (CMP) scaffold to regenerate dead bone for these challenging cases. Ten millilitres of bone marrow was aspirated from iliac crest and
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 peripheral blood
Objectives. In order to ensure safety of the cell-based therapy for bone
regeneration, we examined in vivo biodistribution
of locally or systemically transplanted osteoblast-like cells generated
from bone marrow (BM) derived
The nature of the Aneurysmal Bone Cyst (ABC) is still controversial among benign tumor, often identifiable in the “aggressive” form (Enneking stage 3) or pseudotumoral lesion. It is well known instead the very high risk of intraoperative bleeding, indicating a strongly unfavorable relationship between the surgical morbidity and the nature of the disease. Recently, excellent results have been obtained in the treatment of ABC by repeated arterial embolizations (SAE), without any surgery, while initial experiences with administration of denosumab and doxycycline are still under study. This study presents the results of our initial experience in the treatment of vertebral ABC through the use of concentrated autologous mesenchymal stem cells (MSCs). Two teenagers aged 15 years, male, and 14 years, female, came to our attention both with diagnosis of ABC in C2 vertebra which was histologically confirmed. They were both neurologically intact, the girl complained of neck pain. The arteriography showed in both cases close relationships between the pathological ABC vascularization and the vertebral and cervical ascending arteries, making treatment by selective arterial embolization unsuitable. After discussion with the parents of patients, we jointly decided to undertake the treatment by direct injection of MSCs preceded, in the same operative session, by harvesting from the iliac crest of 60 cc of bone marrow (by needle aspiration) and its separation with the use of concentration system Res-Q ™ 60 BMC. In the second case the treatment was repeated two times at distance of 4 months. The clinical and radiological follow-up is to of 30 months from the first treatment in both cases. In the first case the presence of newly formed bone within the ABC appeared as a clear sign of recovery just a month after the first treatment and increased gradually, until the cyst appeared completely ossified one year after the treatment, with associated disappearance of the pain. In the second case an initial sclerotic peripheral margin appeared after the second treatment and later ossification progressed, concurrently with the disappearance of the pain. Treatment with selective serial arterial embolization is considered effective in the treatment of ABC even if not without risks, mainly related to the frequent and repeated exposure to ionizing radiation. Furthermore, in a certain percentage of cases the procedure is not technically executable, especially for the presence of arteries afferent to the medullar vascularization. Inconsistent results were obtained with other procedures: the injection of calcitonin, steroid, alcoholic solutions, or the use of sclerosing substances. Radiation therapy, though very effective, it is not considered the first choice. Recently, promising results have been achieved by the injection of
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 peripheral blood
Aim of the study was to evaluate if abrasion-arthroplasty (AAP) and abrasion-chondroplasty (ACP) leads to a release of mesenchymal stem cell (MSC) like cells from the bone marrow to the joint cavity where they probably differentiate into a chondrogenic phenotype. Introduction. Cartilage demage is a sever problem in our aging society. About 5 million people only in Germany are affected. Osteoathritis is a degeneration of cartilage caused by aging or traumata 50 % of the people over 40 have signs of osteoarthritis. But the ability of self-regeneration of cartilage is strongly limited. There are different approaches to therapy osteoathritic lesions. Arthroscopic treatment of OA includes bone marrow stimulation technique such as abrasion arthroplasty (AAP) and microfracturing (MF). Beside the support of chondrocyte progenitor cells the environment is also important for the commitment to chondrocytes. Therefore insulin-like growth factor-1 (IGF-1) and transforming growth factor beta-1 (TGF-β1) are important factors during the regeneration process. In the present study we characterised the heamarthrosis and the released cells after AAP and its ability to differentiate into the chondrocyte lineage. Material and Methods. Postoperative haemarthrosis was taken 5, 22 or 44 hours after surgery. 7.5 mg Dexamethasone (Corticosteroid) was administered into the knee joint to prevent postoperative inflammation.
Summary. We demonstrate that osteoclast-like cells of GCT result from the spontaneous fusion and differentiation of CD14+ cells of the monoblastic lineage by an autocrine mechanism mediated by RANKL, rather than induced by stromal cells. This process is further enhanced by the simultaneous impairment of the negative feed-back regulation of osteoclastogenesis by interferon β. Introduction. Giant cell tumor of bone (GCT) is a benign osteolytic lesion with a complex histology, comprising prominent multinucleated osteoclast-like
Various chemicals are commonly used as adjuvant treatment to surgery for giant-cell tumour (GCT) of bone. The comparative effect of these solutions on the cells of GCT is not known. In this study we evaluated the cytotoxic effect of sterile water, 95% ethanol, 5% phenol, 3% hydrogen peroxide (H2O2) and 50% zinc chloride (ZnCI2) on GCT monolayer tumour cultures which were established from six patients. The DNA content, the metabolic activity and the viability of the cultured samples of tumour cells were assessed at various times up to 120 hours after their exposure to these solutions. Equal cytotoxicity to the GCT monolayer culture was observed for 95% ethanol, 5% phenol, 3% H2O2 and 50% ZnCI2. The treated samples showed significant reductions in DNA content and metabolic activity 24 hours after treatment and this was sustained for up to 120 hours. The samples treated with sterile water showed an initial decline in DNA content and viability 24 hours after treatment, but the surviving cells were viable and had proliferated. No multinucleated cell formation was seen in these cultures. These results suggest that the use of chemical adjuvants other than water could help improve local control in the treatment of GCT of bone.
Mesenchymal stem cells have the ability to differentiate into various cell types, and thus have emerged as promising alternatives to chondrocytes in cell-based cartilage repair methods. The aim of this experimental study was to investigate the effect of bone marrow derived mesenchymal stem cells combined with platelet rich fibrin on osteochondral defect repair and articular cartilage regeneration in a canine model. Osteochondral defects were created on the medial femoral condyles of 12 adult male mixed breed dogs. They were either treated with stem cells seeded on platelet rich fibrin or left empty. Macroscopic and histological evaluation of the repair tissue was conducted after four, 16 and 24 weeks using the International Cartilage Repair Society macroscopic and the O’Driscoll histological grading systems. Results were reported as mean and standard deviation (Objectives
Methods