1,721,069 research outputs found
Osteosarcopenia in hip fracture: taking cues from pathophysiology for clinical practice
No full text: Hip fractures are common in older and frail adults, and the risk of adverse outcomes and mortality is significantly increased in patients affected by osteosarcopenia. Identifying particularly vulnerable subjects is a critical step to act aimed at promoting postoperative recovery and reducing the risk of adverse events. However, the diagnostic criteria that are currently used to establish the severity of osteosarcopenia are not easily applicable in patients with hip fractures and impaired mobility. In this review, the new knowledge on the pathophysiology of osteosarcopenia that provides several cues for studying biomarkers potentially useful in clinical practice is summarized. Although significant progress has been obtained in understanding the biological mechanisms leading to the involution of the bone- muscle unit, further studies are needed to identify clinically relevant biomarkers and their diagnostic accuracy in establishing the severity of the osteosarcopenia, predicting adverse outcomes, and guiding physicians in choosing appropriate therapeutic interventions
The Combined Use of Mesenchymal Stromal Cells and Scaffolds for Bone Repair
No full textA 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
Role of citrate in pathophysiology and medical management of bone diseases
Full text linkCitrate is an intermediate in the “Tricarboxylic Acid Cycle” and is used by all aerobic organisms to produce usable chemical energy. It is a derivative of citric acid, a weak organic acid which can be introduced with diet since it naturally exists in a variety of fruits and vegetables, and can be consumed as a dietary supplement. The close association between this compound and bone was pointed out for the first time by Dickens in 1941, who showed that approximately 90% of the citrate bulk of the human body resides in mineralised tissues. Since then, the number of published articles has increased exponentially, and considerable progress in understanding how citrate is involved in bone metabolism has been made. This review summarises current knowledge regarding the role of citrate in the pathophysiology and medical management of bone disorders
Is the high superior tension technique an equivalent substitute for progressive tension sutures in postbariatric abdominoplasty? A comparison prospective study.
No full textBACKGROUND:
The addition of progressive tension sutures to the abdominoplasty technique is advocated to reduce the risk of several complications. High superior tension abdominoplasty is another technique aimed at reducing tension at the prepubic suture line and improving cosmesis of the umbilical area.
METHODS:
A cohort of massive weight loss patients undergoing abdominoplasty, treated with the progressive tension suture technique in association with the high superior tension technique (group A), was followed up and compared to a cohort of patients who underwent high superior tension abdominoplasty (group B). Several variables including rate of complications and patient satisfaction were explored to determine any possible benefit deriving from the combination of progressive tension suture and high superior tension techniques in the abdominoplasty.
RESULTS:
A total of 90 patients were included in the study, of whom 34 were in group A and 56 were in group B. No statistically significant difference was found between the two groups in terms of duration of the procedure, hospitalization time, rate of complications, drained volume, and patient or physician satisfaction.
CONCLUSION:
No beneficial effect appears to derive from the progressive tension suture technique in massive weight loss patients undergoing abdominoplasty, provided that the high superior tension technique is performed as an adjunct to the traditional method
Hypoxia enhances proliferation and stemness of human adipose-derived mesenchymal stem cells
No full textThe aim of the study was to obtain the highest number of multipotent adipose-derived mesenchymal stem cells (ADMSCs) by using culture conditions which favour cell expansion without loss of mesenchymal stem cells (MSC)-like properties. Based on the assumption that stem cells reside in niches characterized by hypoxic condition, we investigated if the low oxygen tension may improve the proliferation and stemness of ADMSCs. Intact adipose tissue was resected from eight subjects, and the stromal vascular fraction was obtained by using type II collagenase. The heterogeneity of cellular lineages was confirmed by immunophenotypic analysis that showed the presence of leukocytes (CD45+), endothelial cells (CD34+), and pericytes (CD140+). The immunophenotype of confluent ADMSCs was similar to that of bone marrow-derived MSCs, except for the expression of CD34, which was variable (donor-dependent) and inversely correlated to the CD36 expression. ADMSCs showed a high clonal efficiency (94.5 ± 1 %) and were able to generate osteoblastic, chondrocytic and adipocytic lineages. ADMSCs were cultured under normoxic (21 % O2) and hypoxic (1 % O2) conditions, and we found that hypoxia significantly favoured ADMSC proliferation and preserved the expression of stemness genes, i.e. Nanog and Sox2. Since hypoxia reflects the microenvironment in which ADMSCs must proliferate and differentiate, the culture in hypoxic condition allows to better understand the biology of these cells and their regenerative potential. Low oxygen concentrations promote cell proliferation and stemness, thus enriching the pool of cells potentially able to differentiate into multi-lineages, and extending the possibility of a long-term expansion
Metal hypersensitivity testing in patients undergoing joint replacement: A systematic review.
No full textWe report a systematic review and meta-analysis of the peer-reviewed literature focusing on metal sensitivity testing in patients undergoing total joint replacement (TJR). Our purpose was to assess the risk of developing metal hypersensitivity post-operatively and its relationship with outcome and to investigate the advantages of performing hypersensitivity testing. We undertook a comprehensive search of the citations quoted in PubMed and EMBASE: 22 articles (comprising 3634 patients) met the inclusion criteria. The frequency of positive tests increased after TJR, especially in patients with implant failure or a metal-on-metal coupling. The probability of developing a metal allergy was higher post-operatively (odds ratio (OR) 1.52 (95% confidence interval (CI) 1.06 to 2.31)), and the risk was further increased when failed implants were compared with stable TJRs (OR 2.76 (95% CI 1.14 to 6.70)). Hypersensitivity testing was not able to discriminate between stable and failed TJRs, as its predictive value was not statistically proven. However, it is generally thought that hypersensitivity testing should be performed in patients with a history of metal allergy and in failed TJRs, especially with metal-on-metal implants and when the cause of the loosening is doubtfu
Effects of osteogenic differentiation inducers on in vitro expanded adult mesenchymal stromal cells.
No full textPURPOSE:
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
Plasma levels of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in patients with neuroblastoma
No full textMicroRNA expression profiling of human bone marrow mesenchymal stem cells during osteogenic differentiation reveals Osterix regulation by miR-31.
No full textOsteogenesis is the result of a complex sequence of events that involve the differentiation of mesenchymal stem cells (MSC) into osteoblasts. MSCs are multipotent adult stem cells that can give rise to different cell types of the mesenchymal germ layer. The differentiation fate of MSCs depends on the microenvironmental signals received by these cells and is tightly regulated by multiple pathways that lead to the activation of specific transcription factors. Among the transcription factors involved in osteogenic differentiation Osterix (Sp7) plays a key role and has been shown to be fundamental for bone homeostasis. However, the molecular events governing the expression of this transcription factor are not fully understood. In this study we set out to investigate the changes in the microRNA (miRNA) expression that occur during the osteogenic differentiation of bone marrow-derived MSCs. To this purpose, we analyzed the miRNA expression profile of MSCs deriving from 3 donors during the differentiation and mineralization processes by microarray. 29 miRNAs were significantly and consistently modulated during the osteogenic differentiation and 5 during the mineralization process. Interestingly, most of the differentially expressed miRNAs have been reported to be implicated in stemness maintenance, differentiation and/or oncogenesis. Subsequently, we focused our attention on the regulation of Osterix by miRNAs and demonstrated that one of the miRNAs differentially modulated during osteogenic differentiation, miR-31, controls Osterix expression through association to the 3' untranslated region of this transcription factor. By analyzing miR-31 and Osterix expression levels we found an inverse miRNA-target expression trend during osteogenic differentiation and in osteosarcoma cell lines. Moreover, the inhibition of the microRNA activity led to an increase in the endogenous expression of Osterix. Our results define a miRNA signature characterizing the osteogenic differentiation of MSCs and provide evidence for the involvement of miR-31 in the regulation of the bone-specific transcription factor Osterix
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