Terapia celular na obesidade monogênica utilizando microesferas de adipócitos derivados de células-tronco

• Ano de defesa: 2018
• Autor(a) principal: Turaca, Lauro Thiago [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Obesity; Cell therapy; Adipocytes; Leptin; Mesenchymal stem cell; Obesidade; Terapia Celular; Adipócitos; Leptina; Célula-tronco mesenquimal
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6433081; https://repositorio.unifesp.br/handle/11600/53056

Abstract Monogenic obesity is defined as obesity resulting from the mutation or deficiency of a single gene. The cases are rare, very serious, usually of early onset and are found in childhood. These types of obesity are usually linked to excess food intake, altered energy expenditure and adipogenesis. Severe mutations in the leptin gene, an adipokine linked to the control of food intake, generate a type of morbid obesity with high infection rates and infant mortality. Some studies have shown the dramatic and beneficial effects of daily use of subcutaneous injections of leptin to reduce body weight. Other studies have focused on strategies that combine the use of stem cells with tissue engineering technologies in order to act as a mechanism for replacing this molecule. In this study adipose tissue cells submitted to adipogenesis (ADASC) were used to verify the reversal of obesity in ob / ob mice. These animals are obese due to a point mutation in the leptin gene and were transplanted with ADASC in microspheres format. The developed microspheres have a diameter of 250μm and showed a higher retention capacity at the transplanted site when compared to isolated cells. The results show that a single dose of 530 microspheres was able to reduce the weight of the animals after approximately 100 days. In approximately two months, only the group that received ADASC microspheres had circulating leptin (75% of the animals). After three months the weight of the animals receiving microspheres reduced 14.7% in relation to the initial weight and 27.5% in relation to the weight of the control group. On the other hand, the group isolated cells increased the weight by 4.8% in relation to the initial one and decreased 8.0% in relation to the control. The results indicate a proposed microsphereshaped cell therapy that may result in the reversal of morbid obesity or even other types of monogenic diseases.