Análise dos nichos nas doenças primárias, secundárias e reacionais da medula óssea
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Data
2019-03-01
Autores
Augusto, Bruna Pagnin
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Universidade Estadual Paulista (Unesp)
Resumo
Introdução: A medula óssea é o órgão responsável pela hematopoise, fenômeno que se relaciona com a diferenciação da célula tronco hemopoética (CTH) em eritrócitos, granulócitos, monócitos, linfócitos e plaquetas. É constituída pelo tecido hematopoiético, tecido gorduroso, matriz proteica e sinusoidais e está contida no interior dos ossos esponjosos, em contato com o tecido ósseo cortical e trabecular. Em 1978, Ray Schofield conceituou nicho como local especifico, dentro da medula óssea, onde a CTH se origina, assenta e prolifera. Atualmente sabe-se que o nicho é mais do que um simples compartimento morfológico, mas um sítio funcional e dinâmico, que se remodela e influencia a função da CTH e suas progenitoras, exercendo papel definitivo na CTH normal e neoplásica. Estudos demonstram que os nichos e seus componentes celulares e proteicos, influenciam e determinam a manutenção de CTH ativas e quiescentes, sendo determinante na manutenção, progressão e recaída de doenças da medula óssea. Objetivo: O objetivo deste trabalho foi avaliar na medula óssea humana, acometida por doenças primárias, secundárias e reacionais, o comportamento da CTH, descrevendo localização e quantificação destas. Material e métodos: Para realização deste estudo, foram selecionados quatro grupos de doenças hematológicas, divididas em mieloma múltiplo (n= 10), leucemia linfóide crônica (n= 10), síndrome mielodisplásica (n= 10) e reacional (n= 10). Foi realiado um estudo imuno-histoquímico para avaliação da marcação e dos nichos dos marcadores CD44, CD34, CD31 e CD117. Resultados: O marcador CD44, molécula de adesão importante na manutenção de CTH e nicho de células tumorais, foi encontrado em maior quantidade durante o estudo, e principalmente no nicho 2. Também foi possível observar que em neoplasias hematológicas, existe uma marcação positiva no nicho 3, sugerindo assim, uma ativação e migração das CTH para outros microambientes. Conclusão: De todos os marcadores estudados, o CD44 é o que teve maior importância e impacto no funcionamento das CTH, sugerindo que este possa ser considerado um marcador para estudar a biologia das CTH.
Introduction: Bone marrow is the organ responsible for hematopoiesis, a phenomenon that is related to the differentiation of hemopoietic stem cell (HSC) into erythrocytes, granulocytes, monocytes, lymphocytes and platelets. It consists of hematopoietic tissue, fatty tissue, protein and sinusoidal matrix and is contained within the spongy bones, in contact with the cortical and trabecular bone tissue. In 1978, Ray Schofield conceptualized a niche as a specific site within the bone marrow, where the HSC originated, settled, and proliferated. It is now known that the niche is more than a simple morphological compartment, but a functional and dynamic site, which remodels and influences the function of HSC and its progenitors, playing a definitive role in normal and neoplastic HSC. Studies demonstrate that niches and their cellular and protein components influence and determine the maintenance of active and quiescent HSC, being determinant in the maintenance, progression and relapse of diseases of the bone marrow. Objective: The aim of this study was to evaluate the behavior of HSC in the human bone marrow, affected by primary, secondary and reactional diseases, describing their location and quantification. Materials and methods: Four groups of hematological diseases were selected, divided into multiple myeloma (n = 10), chronic lymphocytic leukemia (n = 10), myelodysplastic syndrome (n = 10) and reactional (n = 10). An immunohistochemical study was performed to evaluate the marking and niches of the CD44, CD34, CD31 and CD117 markers. Results: The CD44 marker, an important adhesion molecule in the maintenance of CTH and tumor cell niche, was found in greater quantity during the study, and especially in the niche 2. It was also possible to observe that in hematological malignancies, there is a positive marking in the niche 3, thus suggesting an activation and migration of the HTCs to other microenvironments. Conclusion: Of all the markers studied, CD44 is the one that had the greatest importance and impact on the functioning of HTCs, suggesting that it could be considered a marker to study the biology of HTCs
Introduction: Bone marrow is the organ responsible for hematopoiesis, a phenomenon that is related to the differentiation of hemopoietic stem cell (HSC) into erythrocytes, granulocytes, monocytes, lymphocytes and platelets. It consists of hematopoietic tissue, fatty tissue, protein and sinusoidal matrix and is contained within the spongy bones, in contact with the cortical and trabecular bone tissue. In 1978, Ray Schofield conceptualized a niche as a specific site within the bone marrow, where the HSC originated, settled, and proliferated. It is now known that the niche is more than a simple morphological compartment, but a functional and dynamic site, which remodels and influences the function of HSC and its progenitors, playing a definitive role in normal and neoplastic HSC. Studies demonstrate that niches and their cellular and protein components influence and determine the maintenance of active and quiescent HSC, being determinant in the maintenance, progression and relapse of diseases of the bone marrow. Objective: The aim of this study was to evaluate the behavior of HSC in the human bone marrow, affected by primary, secondary and reactional diseases, describing their location and quantification. Materials and methods: Four groups of hematological diseases were selected, divided into multiple myeloma (n = 10), chronic lymphocytic leukemia (n = 10), myelodysplastic syndrome (n = 10) and reactional (n = 10). An immunohistochemical study was performed to evaluate the marking and niches of the CD44, CD34, CD31 and CD117 markers. Results: The CD44 marker, an important adhesion molecule in the maintenance of CTH and tumor cell niche, was found in greater quantity during the study, and especially in the niche 2. It was also possible to observe that in hematological malignancies, there is a positive marking in the niche 3, thus suggesting an activation and migration of the HTCs to other microenvironments. Conclusion: Of all the markers studied, CD44 is the one that had the greatest importance and impact on the functioning of HTCs, suggesting that it could be considered a marker to study the biology of HTCs
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Palavras-chave
medula óssea, célula tronco hematopoética, microambiente, imuno-histoquímica, bone marrow, hematopoietic stem cell, microenvironment, immunohistochemistry