| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 10.19 MB | Adobe PDF |
Authors
Abstract(s)
A evolução da ciência tem proporcionado novas oportunidades que resultaram num prolongamento e aumento da qualidade da vida humana. Uma dessas descobertas foi a utilização de células estaminais para terapia celular, com o intuito de ajudar a reparar, substituir ou regenerar tecidos ou órgãos. As células estaminais apresentam duas propriedades especiais: o potencial de se diferenciarem em múltiplas linhagens e a capacidade de se auto-renovarem. Existem dois tipos principais de células estaminais, as embrionárias e as adultas. Entre estas últimas, estão as células estaminais mesenquimais que são detentoras de um potencial multipotente, o que as torna muito atractivas para aplicações clínicas, além de serem livres de objecções éticas.
Os dendrímeros são macromoléculas esféricas, com uma estrutura bem definida e com uma superfície multivalente. Os dendrímeros de poli(amidoamina) (PAMAM) foram os primeiros a ser sintetizados, caracterizados e comercializados. Estes podem apresentar diferentes grupos funcionais à superfície que fazem variar as suas propriedades.
De facto, à semelhança do que acontece com outros nanomateriais, é cada vez mais comum a utilização de dendrímeros em associação com as células estaminais mesenquimais, com o intuito de se encontrarem novas abordagens terapêuticas e metodologias de diagnóstico. Posto isto, o objectivo principal desta tese foi verificar se a capacidade de diferenciação osteogénica e adipogénica destas células não era afectada na presença de dendrímeros PAMAM. Desta forma, procedeu-se ao estudo do efeito do tipo de funcionalização à superfície, do número de geração e da concentração de dendrímeros na diferenciação celular. Foi avaliada a citotoxicidade através do teste de redução da resazurina e a capacidade de diferenciação através de marcadores bioquímicos e histoquímicos clássicos comummente utilizados na caracterização de culturas de osteoblastos e adipócitos.
Constatou-se que a viabilidade celular é inferior quando as culturas se encontram em contacto com dendrímeros carregados positivamente, enquanto que com dendrímeros aniónicos ou neutros não sofre nenhuma alteração. Em termos da diferenciação, mostrou-se que esta não é directamente afectada pela exposição aos dendrímeros.
The evolution of science has provided new opportunities that resulted in prolonged and improved quality of life. One of these findings was the use of stem cells for cellular therapies, with the aim of repairing, substitute or regenerate tissues or organs. Stem cells present two major properties: the capacity of differentiation into multiple lineages and the capacity of self-renew. There are two types of stem cells, the embryonic and the adult. Among the latter are the mesenchymal stem cells which are multipotent and free of ethical issues, being thus attractive for clinical applications. The dendrimers are spherical macromolecules with a very well defined structure and with a multivalent surface. The poly(amidoamine) (PAMAM) dendrimers were the first ones being synthesized, characterized and commercialized. They can present different surface groups which are responsible for their properties. In fact, in similarity with what happens with other nanomaterials, the use of dendrimers in association with mesenchymal stem cells is becoming common for finding new diagnostic methodologies and therapeutic strategies. The main goal of this thesis was, then, to evaluate if the osteogenic and adipogenic differentiation potential of mesenchymal stem cells was not affected by the presence of PAMAM dendrimers. For that purpose, the effect of the type of surface functional groups, generation number and concentration of dendrimers on cellular differentiation was studied. Cell viability was assessed by the resazurin reduction assay and the differentiation capacity through classic biochemical and histochemical parameters commonly used in the characterization of osteoblasts and adipocytes in culture. Results have shown that cell viability was lower when the cultures were in contact with cationic dendrimers, whereas, with anionic and neutral dendrimers there was no change. On the other hand, cell differentiation was not directly affected by exposure to dendrimers.
The evolution of science has provided new opportunities that resulted in prolonged and improved quality of life. One of these findings was the use of stem cells for cellular therapies, with the aim of repairing, substitute or regenerate tissues or organs. Stem cells present two major properties: the capacity of differentiation into multiple lineages and the capacity of self-renew. There are two types of stem cells, the embryonic and the adult. Among the latter are the mesenchymal stem cells which are multipotent and free of ethical issues, being thus attractive for clinical applications. The dendrimers are spherical macromolecules with a very well defined structure and with a multivalent surface. The poly(amidoamine) (PAMAM) dendrimers were the first ones being synthesized, characterized and commercialized. They can present different surface groups which are responsible for their properties. In fact, in similarity with what happens with other nanomaterials, the use of dendrimers in association with mesenchymal stem cells is becoming common for finding new diagnostic methodologies and therapeutic strategies. The main goal of this thesis was, then, to evaluate if the osteogenic and adipogenic differentiation potential of mesenchymal stem cells was not affected by the presence of PAMAM dendrimers. For that purpose, the effect of the type of surface functional groups, generation number and concentration of dendrimers on cellular differentiation was studied. Cell viability was assessed by the resazurin reduction assay and the differentiation capacity through classic biochemical and histochemical parameters commonly used in the characterization of osteoblasts and adipocytes in culture. Results have shown that cell viability was lower when the cultures were in contact with cationic dendrimers, whereas, with anionic and neutral dendrimers there was no change. On the other hand, cell differentiation was not directly affected by exposure to dendrimers.
Description
Keywords
Células estaminais Células estaminais mesenquimais Dendrímeros Dendrímeros - Aplicação médica
Pedagogical Context
Citation
Publisher
Universidade da Beira Interior