Browsing by Subject "Growth factors"

Now showing 1 - 9 of 9
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    Adipose-derived stem cells and adipose-derived stem cell-conditioned medium modulate in situ imbalance between collagen I- and collagen V-mediated IL-17 immune response recovering bleomycin pulmonary fibrosis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Gonçalves Felix, Renato; Carvalho Bovolato, Ana Livia; Cotrim, Ondina Silvia; Leão, Patricia dos Santos; Batah, Sabrina Setembre; Golim, Márjorie de Assis; Velosa, Ana Paula P.; Teodoro, Walcy; Martins, Vanessa; Ferreira Cruz, Fernanda; Deffune, Elenice; Fabro, Alexandre Todorovic; Capelozzi, Vera Luiza
    The immunogenic collagen V (Col V) and the proinflammatory cytokine interleukin (IL)-17 have been implicated in the pathogenesis of multiple autoimmune diseases. Col V is also up-regulated during adipogenesis and can stimulate adipocyte differentiation in vitro. Conditioned medium (CM) generated from adipose- derived mesenchymal stem cells (MSCs) reduces bleomycin (BLM)-induced lung injury in rats, suggesting a crucial role in situ of immunomodulatory factors secreted by MSCs in these beneficial effects. In the present work, we investigated this hypothesis, analyzing levels of plasma inflammatory mediators and inflammatory and fibrotic mediators in the lung tissue of BLM-injured rats after treatment with MSCs and CM. Pulmonary fibrosis was intratracheally induced by BLM. After 10 days, BLM animals were further randomized into subgroups receiving saline, MSCs, or CM intravenously. On days 14 and 21, the animals were euthanized, and the lungs were examined through protein expression of nitric oxide synthase (NOS), IL-17, transforming growth factor-β (TGF-β), vascular endothelial growth factor, endothelin-1, and the immunogenic Col V through histological quantitative evaluation and plasma levels of fibrinogen, Von Willebrand factor, and platelet-derived growth factor (PDGF). Rats that had been injected with MSCs and CM showed a significant increase in weight and significant improvements at 14 and 21 days after intravenous injection at both time points of analysis of plasma fibrinogen, PDGF, and Von Willebrand factor and NOS-2 expression, supporting an early anti-inflammatory action, thus reducing TGF-β and collagen I fibers. In contrast, intravenous injection of CM was able to significantly increase the deposition of Col V fibers and IL-17 on both day 14 and day 21 as compared with the amount observed in rats from the BLM group and MSC groups. In conclusion, this study reinforces previous observations on the therapeutic properties of MSCs and CM and is the first report to demonstrate the association of its actions with immunomodulatory biomarkers on lung tissue. We concluded that adipose-derived stem cells and adipose- derived stem cells-CM modulate an in situ imbalance between collagen I- and Col V-mediated IL-17 immune response, emerging as a promising therapeutic option for recovering from BLM pulmonary fibrosis
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    Dynamic interactions of the extracellular matrix
    (Murcia : F. Hernández, 1996) Slater, M.
    The extracellular matrix (ECM) is a dynamic assemblage of interacting molecules that reorganise and regulate cell functions in response to endogenous and exogenous stimulii. Matrix components may affect cell behaviour directly or indirectly through growth factor sequestration and transmembrane signalling, by controlling the speed of various molecules through the ECM, and the access of growth factors, hormones and neurotransmitters to the cell surface.
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    Empleo de células madre en el tratamiento de lesiones tendinosas en el caballo de deporte
    (Universidad de Murcia, 2014) Diego, R.
    Los caballos presentan un potente aparato tendinoso en la región distal de sus extremidades que se originan en los sistemas musculares que se disponen proximalmente al carpo o tarso y se insertan en la falange distal. Como consecuencia de las exigencias deportivas a las que están sometidos los caballos, son frecuentes las lesiones tendinosas que comprometen su vida deportiva. Tradicionalmente, el tratamiento se ha basado en regeneradores de la matriz extracelular (polisulfato glicosaminoglicano, ácido hialurónico) o inhibidores del colágeno (β-aminopropionitrilo de fumarato) combinado con reposo, con unos resultados limitados. Es por ello que en la última década se han desarrollado opciones terapéuticas basadas en la medicina regenerativa y la terapia celular, permitiendo la recuperación funcional de la estructura lesionada mediante el uso de células madre mesenquimales (MSCs). En este artículo se revisa el estado actual de la terapia celular con MSCs como tratamiento de lesiones tendinosas en caballos de deporte. A nivel de terapia celular destaca el uso de células madre mesenquimales de origen óseo y adiposo, con unos resultados de recuperación realmente alentadores con respecto a caballos mantenidos en reposo, que se traduce en la presencia en la zona lesionada de un mayor porcentaje de colágeno tipo I, menor cantidad de agua y glucosaminoglicanos y disminución del infiltrado inflamatorio; también se ha descrito un aumento en la neovascularización. En cuanto a las propiedades biomecánicas, los tendones tratados con células madre tienen menor rigidez y mejor organización fibrilar que los tratados de forma clásica, apreciándose también mejoras en la elasticidad. Los datos que ofrecen los últimos estudios, muestran que de los animales tratados con MSCs (n=113), el 98,2% volvió a la vida deportiva. De este 98,2% de caballos, el 27,4% presentó recidivas y el 5,3% tuvo una lesión tendinosa en la extremidad contralateral. Sin embargo, no se han encontrado diferencias en la resolución de tendinopatías tratadas con MSCs por edad ni por sexo. Aunque los resultados de los primeros estudios sean favorables, hasta la fecha, la falta de estandarización de los protocolos y el número reducido de animales estudiados no permiten alcanzar conclusiones definitivas.
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    Extracellular matrix in renal cell carcinomas
    (Murcia : F. Hernández, 1998) Lohi, J.; Leivo, I.; Oivula, J.; Lehto, V.P.; Virtanen, I.
    Extracellular matrix (ECM) may be divided into interstitial matrix and the basement membrane (BM). ECM influences a variety of epithelial cell behaviours, including proliferation, differentiation, and morphogenesis, maybe most widely studied in kidney morphogenesis. In carcinomas, including renal cell carcinomas (RCCs), these properties and interactions of cells with interstitial matrix and BM are disturbed. As a carcinoma with a tendency to spread to distant sites, RCC is an interesting target for the study of epithelialstromal interactions. Among interstitial collagens, type V1 collagen appears to be widely distributed in RCCs. Also EDA-fibronectin (EDA-Fn) as well as tenascin-C (Tn) are important stromal components especially in poorly differentiated carcinomas. BMs of RCC islets and those of tumor blood vessel endothelia may merge in poorly differentiated carcinomas. As a dynamic component of BMs, laminins (Ln) are important in kidney development and RCC progression. Type IV collagen and nidogen, other components of BMs in RCCs, are produced by stromal as well as epithelial cells. ECM proteins may function in RCC progression by binding and regulating the activity of growth factors e.g. transforming growth factor B1 and basic fibroblast growth factor. Also the expression of cell surface receptors for ECM is disturbed in RCCs. At least a, integrin (Int) and CD44 emerge in renal epithelial cells during malignant transformation. Papillary renal neoplasms differ from RCCs by cell adhesion receptor expression and BM composition as well as by ECM avascularity and capacity to bind growth factors, thus suggesting a distinct property for this renal tumor.
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    Histological evaluation of scar tissue inflammatory response: the role of hGH in diabetic rats
    (Murcia : F. Hernández, 2005) García-Esteo, F.; Pascual, G.; García-Honduvilla, N.; Gallardo, A.; San-Román, J.; Bellón, J.M.; Buján, J.
    This paper describes a polymer site-specific delivery system containing human growth hormone in an in vivo model of scarring in the diabetic state. Copolymer discs with the hormone were introduced into incisions made in rats previously injected with streptozotocin in order to induce diabetes. Tissue specimens for evaluation were obtained at 3, 7 or 10 days after the procedure. Study groups were healthy rats and diabetic rats untreated or treated with/without the hormone. Histological sections were prepared for light microscopy examination of wound zones. Three and 7 days after surgery, polymer remains could be observed in the subcutaneous tissue. These remnants induced a moderate foreign body reaction. The number of macrophages detected was directly related to neovessel formation and metalloelastase expression. The CD4+/CD8+ ratio was low during the initial follow up stages (3 and 7 days) in untreated diabetic rats, yet an increased ratio corresponding to areas around the polymer remains was noted in the animals treated with copolymer loaded with the growth hormone. Copolymer is biodegradable in vivo and may be used as a vehicle for the slow release of active substances. The presence of the hormone at the site of skin injury induces cell proliferation and enhances the repair process.
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    In vitro maturation of human primordial ovarian follicles. Clinical significance, progress in mammals, and methods for growth evaluation
    (Murcia : F. Hernández, 2006) Abir, R.; Nitke, S.; Ben-Haroush, A.; Fisch, B.
    As cancer treatment improves, more young women of reproductive age are surviving, but they suffer from infertility as a consequence of the radiation and chemotherapy. Human ovarian tissue containing immature primordial follicles has been successfully cryopreserved. The ultimate aim of this technique is to induce ovarian function by re-plantation of ovarian tissue or, further into the future, by in vitro maturation (IVM) of the oocytes derived from the cryopreservedthawed ovarian tissue, followed by routine in vitro fertilization. IVM of primordial follicles from young cancer survivors would avoid the risk of cancer retransmission by the ovarian grafts. The present review discusses the current achievements in IVM of female germ cells and primordial ovarian follicles and the attempts to improve their development by adding various factors to the culture medium. The established methods for the evaluation of survival and growth in culture are also discussed: follicular counts, immunocytochemical methods, transmission electron microscopy, fluorescent viability markers and endocrine assays. Although the development of IVM systems is still in its infancy, researchers need to pursue their approach step-by-step, especially with regard to factors that might be involved in the activation of the ovarian follicles or female germ cells. The final measure of success will be the ability of the in vitro matured oocytes to fertilize and produce healthy offsprings. The availability of such treatment will probably lead to its demand not only by cancer patients but by other women as well.
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    Molecular signaling in bone fracture healing and distraction osteogenesis
    (Murcia : F. Hernández, 1999) Liu, Z.; Luyte, F.P.; Lammens, J.; Dequeker, J.
    The process of fracture healing has been described in detail in many histological studies. Recent work has focused on the mechanisms by which growth and differentiation factors regulate the fracture healing process. Rapid progress in skeletal cellular and molecular biology has led to the identification of many signaling molecules associated with the formation of skeletal tissues, including members of the transforming growth factor-0 (TGF-B) superfamily and the insulin-like growth factor (IGF) family. Increasing evidence indicates that they are critical regulators of cellular proliferation, differentiation, extracellular matrix biosynthesis and mineralization. Limb lengthening procedure (distraction osteogenesis) is a relevant model to investigate the in vivo correlation between mechanical stimulation and biological responses as the callus is stretched by a proper rate and rhythm of mechanical strain. This model also provides additional insights into the molecular and cellular events during bone fracture repair. TGF-B1 was significantly increased in both the distracted callus and the fracture callus. The increased level of TGF-Bl, together with a low concentration of calcium and an enhanced level of collagen synthesis, was maintained in the distracted callus as long as mechanical strain was applied. Less mineralization is also associated with a low level of osteocalcin production. These observations provide further insights into the molecular basis for the cellular events during distraction osteogenesis.
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    New insights into the normal menstrual cycle-regulatory molecules
    (Murcia : F. Hernández, 2004) Sivridis, E.; Giatromanolaki, A.
    Although the growth and regression of the endometrium is primarily a function of the ovarian hormones, recent studies indicate a potential autocrine/paracrine role for regulatory molecules. Thus, growth factors, angiogenesis stimulating factors and proliferating cell markers are high in the proliferative phase endometrium contributing to its regeneration. At the same time, other proteins promote endometrial cell survival by preventing extracellular matrix degradation and apoptosis. As glandular proliferation persists in the early secretory phase of the menstrual cycle, the activity of some proteins stimulating growth remains unchanged, but declines significantly thereafter, shifting the balance between proliferation and apoptosis in favour of apoptosis. During this period, several other regulatory substances are expressed at high levels, suggesting a role in endometrial maturation. If, however, implantation of a fertilized ovum fails to take place, menstruation occurs probably as the result of matrix metalloprotinases which antagononizes the anti-degradation factors (inhibitors of metalloproteinases). This review examines the changing endometrial patterns of a normal menstrual cycle in relation to these regulatory molecules.
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    Recent advances in hypertrophic scar
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Zhang, Julei; Li, Yan; Bai, Xiaozhi; Li, Yuehua; Shi, Jihong; Hu, Dahai
    Hypertrophic scars (HTS) are predominant diseases after burn and trauma, which cause severe physiological and psychological problems. HTS have been researched for decades, and our knowledge about the mechanisms of HTS formation process has been increasing. However, the effects of currently available prevention and treatment strategies are limited. In this review, we summarize currently known mechanisms and recent studies of HTS, including extracellular matrix, matrix metalloproteinases, fibroblasts, myofibroblasts and their contraction ability, keratinocytes, growth factors, inflammatory and immune response, and stem cell treatment, hoping for a better understanding of HTS generation, development and effective translation to treatment strategies.