Towards direct transdifferentiation of adult human cells to the pancreatic B-cell fate

• Autor(a) principal: Santos, Filipa Inês Rodrigues dos
• Data de Publicação: 2013
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.1/7273
• topic: Ciências biomédicas; Páncreas; Diabetes mellitus; Insulina; Glicémia

Type 1 Diabetes mellitus (T1DM) is one of the most widespread metabolic disorders with epidemic dimension affecting almost 6% of the world’s population. Autoimmune reaction causes selective destruction of the insulin-producing β-cells within the pancreatic islets, leading to both acute and long-term complications. Daily insulin injections treat but no dot cure diabetes. Any progress in obtaining large number of transplantable insulin producing cells would be a major advance towards a cure for the disease. In order to create an alternative source of β-cells we are developing a method to transdifferentiate adult human cells to the beta cell phenotype by direct reprogramming mediated by forced expression of an optimized set of pancreas specific transcription factors. The underlying experimental rationale is that sequential or combinatorial ectopic expression of transcription factors can induce recipient cells to establish a β-cell regulatory state. We cloned a set of transcription factors known to be involved in pancreatic development into viral vectors and used them to transdifferentiate adult human cell types in conditions known to favor β-cell differentiation