1,721,147 research outputs found
Prospective purification of a subpopulation of human synovial mesenchymal stem cells with enhanced chondro-osteogenic potency
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Skeletal tissue engineering: opportunities and challenges
No full textTissue engineering is a field of biomedicine that is growing rapidly and is critically driven by scientific advances in the areas of developmental and cell biology and biomaterial sciences. Regeneration of skeletal tissues is among the most promising areas of biological tissue repair and is providing a broad spectrum of potential clinical applications, including joint resurfacing. The availability of novel tools such as pluripotent stem cells, morphogens, smart biomaterials and gene transfer technologies, makes us dream of many exciting novel therapeutic approaches. Despite these opportunities in regenerative medicine, good clinical practice requires the clinician to question the consistency, reproducibility, validation and appropriate regulation of these new biological treatment
Microenvironment and phenotypic stability specify tissue formation by human articular cartilage-derived cells in vivo
No full textDuring in vitro expansion, adult human articular cartilage-derived cells (RACDC) lose their phenotypic stability and capacity to form cartilage in vivo after 4-6 population doublings (PD). Nevertheless, HACDC can be efficiently expanded for up to 20 PD. Here we show that HACDC can generate cartilage, fibrous tissue, skeletal muscle, bone, and adipocytes depending on the balance between phenotypic stability and environmental cues. When 5 x 10(6) cells were injected intramuscularly into nude mice, early-passage (EP)-HACDC formed cartilage; late-passage (LP)-HACDC formed mostly fibrous tissue, but a limited number of cells contributed to muscle formation. When 0.5 x 10(6) cells were injected into regenerating mouse muscle, both EP- and LP-HACDC integrated with host myofibers and expressed muscle genes, but a number of EP-HACDC maintained collagen type II expression. HACDC seeded into Collagraft and implanted subcutaneously into nude mice formed scattered bone islands displaying immunoreactivity for human osteocalcin, and expressing human bone-specific genes. Importantly, neither collagen type II transcript nor cartilage tissue was detected at 8 weeks after implantation. Myogenic, osteogenic, and adipogenic differentiation was induced in vitro using specific culture conditions. These findings provide evidence that in vivo tissue formation by HACDC is specified by a balance between environmental cues and the inherent phenotypic stability. (C) 2003 Elsevier Science (USA). All rights reserve
In vivo assay and molecular markers for testing the phenotypic stability of cell populations, and selected cell populations for autologous transplantation
No full textGiant cell arteritis: Update on pathogenesis and clinical implications
No full textPurpose of reviewGiant cell arteritis (GCA) is an age-related autoimmune disease with a complex pathogenesis that involves several pathogenic mechanisms. This review provides recent critical insights into novel aspects of GCA pathogenesis.Recent findingsThe use of novel approaches, including multiomic techniques, has uncovered notable findings that broaden the understanding of GCA pathogenesis. TCF1hiCD4+ T cells have been identified as stem-like T cells residing in tertiary lymphoid structures in the adventitia of GCA aortic tissues, which likely supply the pathogenic effector T cells present in vasculitic lesions. Studies have demonstrated that fibroblasts present in GCA-inflamed arteries are not innocent bystanders, but they contribute to arterial inflammation via maintenance of Th1 and Th17 polarisation, cytokine secretion (IL-6, IL-1B, IL-12, and IL-23) and antigen presentation. Additionally, deregulated cellular senescence programs are present in GCA as an accumulation of IL-6 and matrix metalloproteinase 9-producing senescent cells have been identified in vasculitic lesions.SummaryRecent studies have unravelled interesting findings with potentially significant clinical relevance. Stem-like T cells are likely key contributors to vascular disease persistence, and targeted depletion or modulation of these cells holds promise in GCA management. Fibroblast-targeting therapies and senotherapeutics are also exciting prospects in the treatment of GCA
Osteoarthritis year in review 2023: Biology
Full text linkGreat progress continues to be made in our understanding of the multiple facets of osteoarthritis (OA) biology. Here, we review the major advances in this field and progress towards therapy development over the past year, highlighting a selection of relevant published literature from a PubMed search covering the year from the end of April 2022 to the end of April 2023. The selected articles have been arranged in themes. These include 1) molecular regulation of articular cartilage and implications for OA, 2) mechanisms of subchondral bone remodelling, 3) role of synovium and inflammation, 4) role of age-related changes including cartilage matrix stiffening, cellular senescence, mitochondrial dysfunction, metabolic dysfunction, and impaired autophagy, and 5) peripheral mechanisms of OA pain. Progress in the understanding of the cellular and molecular mechanisms responsible for the multiple aspects of OA biology is unravelling novel therapeutic targets for disease modification
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