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Advisor(s)
Abstract(s)
A dor lombar é um sintoma prevalente na população, pois aproximadamente 80% da mesma sofre um episódio pelo menos uma vez na vida. A hérnia discal é relativamente comum, com 5 a 20 casos por 1.000 adultos anualmente. Os tratamentos conservador e cirúrgico têm demonstrado recentemente resultados equivalentes a médio e longo prazo. Além disso, o tratamento inadequado pode provocar danos irreversíveis duradouros nos nervos e dor neuropática nos pacientes com compressão severa da raiz do nervo. A terapia proposta nesta tese, é uma tentativa de abordagem de um tratamento menos invasivo que a cirurgia, mas mais rápido em termos de recuperação em comparação com o tratamento conservador, utilizando as propriedades naturais das células imunes do corpo humano para acelerar a reabsorção do disco intervertebral herniado. Para que esta terapia surja como uma solução possível e viável, primeiramente avaliamos as diferentes caracterizações dos macrófagos, que são os principais atores da reabsorção da hérnia discal, e avaliámos o impacto de diferentes polarizações no poder fagocítico destas células. Com o intuito de escolher os fenótipos ideais para dar um passo em frente no desenvolvimento desta terapia, também comparámos as diferentes polarizações em coculturas indiretas com tecido herniado para compreender o comportamento das diferentes populações de macrófagos no contexto do microambiente da hérnia discal. No final, os fenótipos escolhidos, foram: “M1sLPS”, “M2a”, e “M2c” com a finalidade de melhor compreender e caracterizar as populações escolhidas, e avaliar mais aprofundadamente num futuro próximo o contato destes fenótipos com as amostras de hérnia, possivelmente em contato direto.
Low back pain is a prevalent symptom, as approximately 80% of the population sustains an episode once in their lifetime. Disc degeneration is usually associated with disc herniation. Lumbar disc herniation isrelatively common, with 5 to 20 cases per 1000 adults annually. Over 85 to 90% of patients with an acute herniated disc experience relief of symptoms within 6 to 12 weeks without any treatments. Conservative and surgical treatment have recently demonstrated equivalent outcomes in the medium and long term. Furthermore, inadequate treatment can lead to lasting irreversible nerve damage and neuropathic pain in patients with severe nerve root compression. The therapy proposed in this thesis, is an attempt as an approach to a less invasive treatment than surgery, but faster in terms of recovery in comparison to the conservative treatment, using the natural properties of the immune cells from the human body to accelerate the resorption of the herniated IVD. In order for this therapy to emerge as a possible and feasible solution, firstly we evaluated the different characterizations of the macrophages, the main actors of the hernia resorption, and evaluated the impact of different polarizations in the phagocytic power of these cells. In order to choose the ideal phenotypes to take a step further in the development of this therapy, we also compared the different polarizations in indirect cocultures in order to better understand the behaviour of the different macrophage populations within the hernia tissue microenvironment. In the end, the phenotypes chosen, were: “M1sLPS”, “M2a” and “M2c”, with the purpose of further understanding and characterizing the populations chosen, and evaluate further in contact with the hernia samples, possibly in direct contact.
Low back pain is a prevalent symptom, as approximately 80% of the population sustains an episode once in their lifetime. Disc degeneration is usually associated with disc herniation. Lumbar disc herniation isrelatively common, with 5 to 20 cases per 1000 adults annually. Over 85 to 90% of patients with an acute herniated disc experience relief of symptoms within 6 to 12 weeks without any treatments. Conservative and surgical treatment have recently demonstrated equivalent outcomes in the medium and long term. Furthermore, inadequate treatment can lead to lasting irreversible nerve damage and neuropathic pain in patients with severe nerve root compression. The therapy proposed in this thesis, is an attempt as an approach to a less invasive treatment than surgery, but faster in terms of recovery in comparison to the conservative treatment, using the natural properties of the immune cells from the human body to accelerate the resorption of the herniated IVD. In order for this therapy to emerge as a possible and feasible solution, firstly we evaluated the different characterizations of the macrophages, the main actors of the hernia resorption, and evaluated the impact of different polarizations in the phagocytic power of these cells. In order to choose the ideal phenotypes to take a step further in the development of this therapy, we also compared the different polarizations in indirect cocultures in order to better understand the behaviour of the different macrophage populations within the hernia tissue microenvironment. In the end, the phenotypes chosen, were: “M1sLPS”, “M2a” and “M2c”, with the purpose of further understanding and characterizing the populations chosen, and evaluate further in contact with the hernia samples, possibly in direct contact.
Description
Keywords
Hérnia discal Disco intervertebral Tecido herniado Macrófagos Terapia celular Polarização Fagocitose Reabsorção IVD Hernia Inflammation Cytokines Immunology Inflammatory response Macrophages Cell therapy