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Cardiac Tumours
Published in Mary N. Sheppard, Practical Cardiovascular Pathology, 2022
Arguments concerning the origin of myxomas continue. It is now accepted that they are true neoplasms. DNA analysis of myxomas has shown to be mostly diploid and aneuploid. The cell of origin remains contentious. Ultrastructural studies suggest the tumour cells are most like primitive multipotential mesenchymal cells. The concept that this cell is capable of a wide range of phenotypic differentiation is supported by the reported expression of a wide range of antigens. The myxoma tumour cells often cluster around cells marking as endothelial cells with CD34 (Fig. 7.18), but whether these are just a supporting stroma or an integral part of the tumour is unclear. Cytokeratin may be focally positive if there is a glandular pattern of differentiation. Vimentin is usually positive in the tumour cells. Desmin is most frequently described as negative but smooth muscle actin can be positive in the myxoma cells as well as the stroma. Neuron-specific enolase, S-100 and synaptophysin have all been reported as variably positive (Fig. 7.19). Calretinin is the most useful marker and is strongly positive in all myxoma cells and very useful in differentiating from myxosarcomas which are usually negative (Fig. 7.20).9 Histiocytic/macrophage markers are positive in the stroma. The cells of the embryonic endocardial cushions resemble myxoma cells, and a widely held view is that nests of such cells persist in the endocardium, particularly in the region of the foramen ovale where they may give rise to myxomas but definitive identification of these in adults is lacking.
Gene Therapy in Oral Tissue Regeneration
Published in Vincenzo Guarino, Marco Antonio Alvarez-Pérez, Current Advances in Oral and Craniofacial Tissue Engineering, 2020
Fernando Suaste, Patricia González-Alva, Alejandro Luis, Osmar Alejandro
All these cell types are able to self-renew, as well as to differentiate into osteoblasts, adipocytes, odontoblasts and neural cells. While this methodology proposes restoring the mesenchymal cells derived from the bone marrow, oral cavity or other tissue in the wound area could trigger the repair of damaged tissues. The process of differentiation into a particular lineage is highly complex since it involves the space-time expression of growth and transcriptional factors that act in a hierarchical manner triggering signaling pathways, which in turn activates a pattern of gene expression that results in determining cell identity fate.
Cellular and Molecular Interactions in the Induction of Inflammation in Rheumatic Diseases
Published in Thomas F. Kresina, Monoclonal Antibodies, Cytokines, and Arthritis, 2020
The infiltration of lymphocytes and monocyte-macrophages into the synovium and their release of inflammatory mediators, including the cytokines described in this chapter, are associated with the recruitment and proliferation of synovial fibroblastlike cells and synovial tissue neovascularization (1,2,10,169). These observations suggest that immune cell-synovial cell interactions are involved in the formation and function of the pannus, which is composed of proliferating fibroblasts, numerous small blood vessels, collagen, and inflammatory cells. This hyperplasia of synovial lining cells and fibroblastlike cells is an early and characteristic feature of the synovitis associated with rheumatoid arthritis. The pathologic fibroplasia in arthritis, as well as normal tissue repair, is intimately linked to processes that recruit mesenchymal cells and stimulate them to proliferate at local sites (10,169–171). The inflammatory cell-derived products mediate this cellular accumulation, leading to the excessive levels of collagenase and prostaglandins, which in turn are responsible for connective tissue destruction. Erosion of bone, cartilage, and soft connective tissue occurs primarily in areas adjacent to the pannus.
Biologic and advanced immunomodulating therapeutic options for sarcoidosis: a clinical update
Published in Expert Review of Clinical Pharmacology, 2021
Ogugua Ndili Obi, Elyse E. Lower, Robert P. Baughman
Human derived bone marrow-derived mesenchymal stromal cells (MSCs) have been shown to have multiple immunomodulatory properties. They transform macrophages functionally and phenotypically from active pro-inflammatory (M1) cells to IL-10 producing anti-inflammatory (M2) cells [455–458]. They also induce T-cell anergy and induce tolerance by interfering with the maturation of dendritic cells via STAT-3 signaling [459,460]. Mesenchymal cell therapy has been investigated and found to be safe in COPD, ARDS, IBD, cardiovascular disease, autoimmune disease, IPF and sepsis [461–464]. A large systematic review of infusion (n = 342) or inhalational (n = 57) mesenchymal cell therapy in over 200 patients with acute or chronic respiratory diseases showed that mesenchymal cell therapy was well tolerated in patients with ARDS, COPD, silicosis, idiopathic pulmonary fibrosis (IPF) and PAH without significant adverse events [465]. There is an ongoing study evaluating the safety and feasibility of endobronchial therapy with autologous MSCs in patients with mild to moderate idiopathic pulmonary fibrosis (NCT01919827).
Evaluation of potential anti-fibrotic effect of oleuropein on bleomycin-induced pulmonary fibrosis in rat
Published in Toxin Reviews, 2020
Hamid Reza Khalili, Hamid Reza Adeli Behrooz, Mohammad Reaza Rashidi Nooshabadi, Sahar Geravandi, Mohammad Javad Mohammadi, Hossein Foruozandeh
Following alveolar epithelial damaging, inflammatory cascades began. Then, profibrotic cytokines expressions exaggerate and consequently increase ECM depositions, which propagate to fibrotic lesions (fibroblast “foci”). Consequently, a large variety of growth factors, cytokines, and matrix metalloproteinase release by injured epithelial cell (Park and Lee 2013). Activation, proliferation and migration of mesenchymal cells occur with them and it is suggested as end-stage process responsible for potential organs failure and dysfunction (Kar et al.2015). In this study, through fibrosis model induction by BLM, we assessed the protective and anti-fibrotic effect of OLE on lung fibrosis. OLE and its analogs similar to aforementioned phenolic acids possess potent anti-inflammatory effects and exist in numerous fruit and vegetables so are abundantly available in Mediterranean diet (DePascual-Teresa 2014, Kakkar and Bais 2014, Luo et al.2015).
Limbal Epithelial and Mesenchymal Stem Cell Therapy for Corneal Regeneration
Published in Current Eye Research, 2020
Sachin Shukla, Swapna S Shanbhag, Fatemeh Tavakkoli, Shobhit Varma, Vivek Singh, Sayan Basu
The limbus harbours both epithelial and mesenchymal stem cells. The LESCs reside in the basal layer of the limbal epithelium in the palisades of Vogt whereas LMSCs are present in the limbal stroma sub-adjacent to the limbal basement membrane. The LESCs, and perhaps also the LMSCs, play a vital role in maintaining normal corneal homeostasis and their dysfunction leads to a clinical state of stem cell deficiency. This is perhaps the only known clinical stem cell-deficient condition other than cancer/chemotherapy-induced bone marrow stem cell deficiency. Great progress has been made in this area, with limbal epithelial stem cell therapy being successfully practised worldwide using different surgical approaches. Unlike LESCs, the role of LMSCs in normal homeostasis is not yet completely understood. There is some speculation that the mesenchymal cells are vital to the stromal niche that maintains or modulates the function of the epithelial stem cells. There is also no clinically known state of limbal or corneal mesenchymal stem cell deficiency, and therefore the clinical application of LMSCs differs principally from that of LESCs. However, the therapeutic potential of the LMSCs along with other sources of MSCs in the treatment of blinding corneal stromal pathologies is being enthusiastically explored through pre-clinical and early clinical studies. Since both these cell types are concurrently the subject of intense research and clinical applications, the authors feel that the term ‘Limbal Stem Cells’, should, therefore, be qualified by adding the cell type, epithelial or mesenchymal.