1,721,884 research outputs found

    The Combined Use of Mesenchymal Stromal Cells and Scaffolds for Bone Repair

    No full text
    A general principle of stem cell therapy is to exploit the natural ability of the human body to heal through the process of regeneration. Here, we review the current status of cell therapy based on adult mesenchymal stem cells (MSC) with emphasis on therapeutic application in bone-related diseases. The main issues for an effective bone engineering strategy include: - A sufficient number of bone-forming cells, where cell yield, separation, expansion, commitment, as well as patient age, are all variables to be considered; - An ECM-like scaffold conductive for and informative to cells, where structural/physico-chemical/mechanical parameters, administration form (injectable or free-form), and degradation rate have to be tuned according to the clinical application; - Biochemical signals, such as growth factors/cytokines to induce osteogenic differentiation, where the choice between autogenous or exogenous sourcing, dose, timing, etc. are critical; - An adequate blood supply, provided by angiogenetic factors, pre-vascularization, pre-implant co-culture of vessel and bone progenitors. We also discuss the safety and efficacy of different approaches, as well as bottlenecks hampering rapid translation of adult MSC therapy from the laboratories to the clinics. A central paradigm for the effective regeneration of bone tissue is the re-creation at the site of injury of a microenvironment as close as possible to the natural MSC repository in the body. This would allow adult MSC to serve as cellular factories, i.e. to express paracrine activity in situ by secretion of inflammatory and reparative cytokines and to cooperate with other cells. The results from a wide array of in vitro and in vivo studies, as well as from some clinical trials, are expanding the range of clinical protocols for bone repair, that is the ultimate goal of orthopaedics

    Human bone marrow stromal cells: In vitro expansion and differentiation for bone engineering

    No full text
    Stromal cells from marrow hold a great promise for bone regeneration. Even if they are already being exploited in many clinical settings, the biological basis for the source and maintenance of their proliferation/differentiation potential after in vitro isolation and expansion needs further investigation. Most studies on osteogenic differentiation of marrow stromal cells (MSC) have been performed using bone marrow from the iliac crest. In this study, MSC were derived from spare femoral bone marrow obtained during hip replacement surgery from 20 adult donors. After in vitro isolation the cells were grown in osteogenic medium, and their proliferation and differentiation analysed during in vitro expansion. We found that MSC isolated from the femur of adult patients consistently maintain an osteogenic potential. Using biochemical signals, these cells turn to fully differentiated osteoblasts with a predictable set of molecular and phenotypic events of in vitro bone deposition. When seeded on polycaprolactone-based scaffold or surfaces, the proliferation and mineralization of femur-derived MSC were modulated by the surface chemistry/topography. Despite remarkable differences between individual colony-forming ability, alkaline phosphatase production, and mineralization ability, these cells are a potential source for bone engineering, either by direct autologous reimplantation or by ex vivo expansion and reimplantation combined to a proper scaffold

    Isolation, characterisation and osteogenic potential of human bone marrow stromal cells derived from the medullary cavity of the femur

    No full text
    Marrow stromal cells (MSC) are increasingly being introduced in orthopaedic practice as potentially powerful effectors of bone regeneration. Since cell recovery of MSC is affected by a high degree of individual variability, sources for collecting adequate amounts of safe and effective MSC under routine conditions are needed. We analysed if femoral bone marrow, which is usually discarded during total hip arthroplasty procedures, is a reliable source of MSC to enhance bone healing and regeneration. Mononuclear cells were isolated, assayed for typical MSC markers, harvested under appropriate culture conditions and evaluated for their ability to differentiate into osteoblasts. Cell recovery and osteogenic potential were independent from donor gender or age, suggesting that elderly individuals are eligible for autologous cell therapy. Although heterogeneous, the pool of MSC recoveredfrom femoral marrow without further in vitro selection or manipulation proved highly effective in proliferating and differentiating along the osteogenic lineage. In conclusion, this source of MSC offers a valuable tool to be used to promote osteogenesis and implant fixation

    Effects of osteogenic differentiation inducers on in vitro expanded adult mesenchymal stromal cells.

    No full text
    PURPOSE: For bone regeneration therapy using stem cells, well-defined ex vivo protocols to expand mesenchymal stromal cells (MSC), as well as assays to show their potential differentiation into the osteogenic lineage, are needed. Aim of this study was to analyze the role of the biochemical osteogenic inducers, i.e. ascorbic acid, dexamethasone, and ß-glycerophosphate, employed in the current protocols for osteogenic differentiation of MSC in vitro, to address the requirements for reliable differentiation systems. METHODS: MSC were isolated from the bone marrow of donors (46-73 years of age) undergoing total hip replacement, and expanded in vitro. At confluence, MSC were cultured under four different conditions: α-MEM plus serum (basal medium or C1), basal medium plus ascorbate (C2), basal medium plus ascorbate and dexamethasone (C3), or basal medium plus ascorbate, dexamethasone and ß-glycerophosphate (C4). Morphology, proliferation, mineralization, alkaline phosphatase, collagen and expression of bone-related genes of MSC under the different media were analyzed at fixed time points. RESULTS: MSC proliferation and the number of colony forming units were increased by ascorbic acid, whereas dexamethasone enhanced the proportion of ALP-positive CFU and was critical for mineral deposition. Runx-2 and type I collagen gene expression decreased along with additive-induced MSC differentiation, i.e. from C1 to C4, while ALP and osteocalcin were differently regulated. CONCLUSION: Our findings support the role of different inducers on the sequential stages of MSC expansion and osteogenic differentiation in vitro, suggesting the addition of DEX following proliferation to ensure mineralization, as an index of in vivo osteogenic potency of human mesenchymal cells

    Dati preliminari sulle reazioni immunologiche indotte dal gel di PVP

    No full text
    Sono state studiate le modificazioni immunitarie indotte dal polivinilpirrolidone in pazienti portatrici da almeno due anni di protesi mammarie contenenti tale sostanza come gel.; si à valutata la composizione delle sottopopolazioni linfocitarie, l’attivazione e la proliferazione dei linfociti e l’attività delle cellule natural killer. Sembrerebbe che, pur essendo il PVP in grado di indurre un’attivazione immunitaria paragonabile a quella indotta dal silicone, in realtà tale attivazione non si verifichi, forse a causa della rapida eliminazione della sostanza, eventualmente presente nel torrente circolatorio, per via renal

    Strontium Functionalization of Biomaterials for Bone Tissue Engineering Purposes: A Biological Point of View

    Full text link
    Strontium (Sr) is a trace element taken with nutrition and found in bone in close connection to native hydroxyapatite. Sr is involved in a dual mechanism of coupling the stimulation of bone formation with the inhibition of bone resorption, as reported in the literature. Interest in studying Sr has increased in the last decades due to the development of strontium ranelate (SrRan), an orally active agent acting as an anti-osteoporosis drug. However, the use of SrRan was subjected to some limitations starting from 2014 due to its negative side effects on the cardiac safety of patients. In this scenario, an interesting perspective for the administration of Sr is the introduction of Sr ions in biomaterials for bone tissue engineering (BTE) applications. This strategy has attracted attention thanks to its positive effects on bone formation, alongside the reduction of osteoclast activity, proven by in vitro and in vivo studies. The purpose of this review is to go through the classes of biomaterials most commonly used in BTE and functionalized with Sr, i.e., calcium phosphate ceramics, bioactive glasses, metal-based materials, and polymers. The works discussed in this review were selected as representative for each type of the above-mentioned categories, and the biological evaluation in vitro and/or in vivo was the main criterion for selection. The encouraging results collected from the in vitro and in vivo biological evaluations are outlined to highlight the potential applications of materials’ functionalization with Sr as an osteopromoting dopant in BTE
    corecore