1,720,983 research outputs found
The role of osteogenic cells in the pathophysiology of Paget's disease
No full text[No abstract available
The pathology of fibrous dysplasia and the McCune-Albright syndrome
No full textFibrous dysplasia (FD) is the most serious and least understood clinical expression in patients with activating mutations of the GNAS gene. Since the discovery of the causative mutation, important progress has been made in the understanding of the pathology of FD and the pathogenesis of bone lesions. The histology of FD has been reinterpreted in light of the pathological effect of the genetic lesions on mutated skeletal stem cells. True histological hallmarks of the disease have emerged, along with genetic analysis, as additional tools to establish the correct diagnosis. Furthermore, the recognition of FD as a disease of excess, abnormal and imperfect bone formation has helped to explain relevant mechanisms of its clinical morbidity, based on which potential specific therapeutic approaches may be developed in the near future
Stem cells in tissue engineering
No full textThe concept of producing 'spare parts' of the body for replacement of damaged or lost organs lies at the core of the varied biotechnological practices referred to generally as tissue engineering. Use of postnatal stem cells has the potential to significantly alter the perspective of tissue engineering. Successful long-term restoration of continuously self-renewing tissues such as skin, for example, depends on the use of extensively self-renewing stem cells. The identification and isolation of stem cells from a number of tissues provides appropriate targets for prospective gene therapies
The role of stem cells in fibrous dysplasia of bone and the McCune-Albright Syndrome
No full textStem cells have become a major area of interest in the treatment of human disease, but more recently, stem cells have come to be appreciated as the cause of disease. Fibrous dysplasia of bone and the McCune-Albright Syndrome evolve from activating missense mutations in Gsα in pluripotent embryonic stem cells. The legacy of these mutations remains in a population of mutated multipotent post-natal skeletal stem cells ("mesenchymal" stem cells), which direct the formation of abnormal bone and a fibrotic marrow in fibrous dysplasia. Future therapeutic approaches for the treatment of fibrous dysplasia, the most significant component of the McCune-Albright Syndrome, will depend on a greater understanding of post-natal skeletal stem cell biology and how skeletal stem cells can be manipulated for efficient bone regeneration
Bone marrow stromal stem cells: Nature, biology, and potential applications
No full textBone marrow stromal cells are progenitors of skeletal tissue components such as bone, cartilage, the hematopoiesis-supporting stroma, and adipocytes, In addition, they may be experimentally induced to undergo unorthodox differentiation, possibly forming neural and myogenic cells. As such, they represent an important paradigm of post-natal nonhematopoietic stem cells, and an easy source for potential therapeutic use, Along with an overview of the basics of their biology, we discuss here their potential nature as components of the vascular wall, and the prospects for their use in local and systemic transplantation and gene therapy
Mesenchymal stem cells: Revisiting history, concepts, and assays
No full textThe concept of mesenchymal stem cells has gained wide popularity. Despite the rapid growth of the field, uncertainties remain with respect to the defining characteristics of these cells, including their potency and self-renewal. These uncertainties are reflected in a growing tendency to question the very use of the term. This commentary revisits the experimental origin of the concept of the population(s) referred to as mesenchymal stem cells and the experimental framework required to assess their sternness and function
Osteomalacic and hyperparathyroid changes in fibrous dysplasia of bone: Core biopsy studies and clinical correlations
No full textDeposition, mineralization, and resorption of FD bone compared with unaffected bone from FD patients was investigated in iliac crest biopsy specimens from 13 patients. Compared with unaffected bone, lesional FD bone seemed to be very sensitive to the effects of PTH and renal phosphate wasting, which respectively bring about hyperparathyroid or osteomalacic changes in the lesional bone. INTRODUCTION: Fibrous dysplasia is a genetic noninherited disease caused by activating mutations of the GNAS1 gene, resulting in the deposition of qualitatively abnormal bone and marrow. This study was designed to learn more about the local processes of bone deposition, mineralization, and resorption within lesional fibrous dysplasia (FD) bone compared with unaffected bone of FD patients. METHODS: Histology, histomorphometry, and quantitative back-scattered electron imaging (qBSE) analysis was conducted on affected and unaffected biopsy specimens from 13 patients and correlated to markers of bone metabolism. RESULTS AND CONCLUSIONS: There was a marked excess of unmineralized osteoid with a nonlamellar structure and a reduced mineral content in mineralized bone within FD lesions (p < 0.001). A negative correlation (p = 0.05) between osteoid thickness (O.Th) and renal tubular phosphate reabsorption (measured as TmP/GFR) was observed for lesional bone, but not for unaffected bone, in which no histological or histomorphometric evidence of osteomalacia was observed in patients with renal phosphate wasting. Histological and histomorphometric evidence of increased bone resorption was variable in lesional bone and correlated with serum levels of parathyroid hormone (PTH). Hyperparathyroidism-related histological changes were observed in fibrous dysplastic bone, but not in the unaffected bone, of patients with elevated serum PTH secondary to vitamin D deficiency. Our data indicate that, compared with unaffected bone, lesional FD bone is very sensitive to the effects of PTH and renal phosphate wasting, which, respectively, bring about hyperparathyroid or osteomalacic changes in the lesional bone. Osteomalacic and hyperparathyroid changes, which emanate from distinct metabolic derangements (which superimpose on the local effects of GNAS1 mutations in bone), influence, in turn, the severity and type of skeletal morbidity in F
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