lnduced Pluripotent Stem cells disease modeling: approaching Gaucher and Tay Sachs
Year: 2013
Type: dissertation
Abstract: IPSC are potent tools in the creation of disease models for both basic studies on the disease and testing of potential therapeutical drugs. In this context, it has been developed the derivation of iPSC from patient fibroblasts suffering from Gaucher Disease (GD) or Tay Sachs disease (TS).\n\t\t\t\t GD is a recessive autosomic disease which is characterized by the deficiency of the enzyme called glucocerebrosidase (GBA), which leads to the accumulation of its substrate glucosylceramide in macrophages and neurons. This disease has 3 forms of clinical presentation: type I, which is systemic; type II, the most severe with a neuronopathic acute presentation; type III, which is a combination of the former two, but without the severity of the type II.\n\t\t\t\t Tay Sachs is an autosomic recessive disease which is characterized by the Hexosaminidase A (HexA) deficiency, which leads to GM2 accumulation on the lysosomes of neurons. Patients present neurodegeneration and severe impairment of the brain which ultimately leads to their death.\n\t\t\t\t In this project iPSC derived from GD and TS patient fibroblasts. Pluripotent state of the derived iPSC has been characterized. Later, iPSC have been differentiated to neurons in order to confirm the disease phenotype on the in vitro differentiated tissue. In GD the phenotype was corroborated by enzymatic assays and GBA detection by Western blot. A lower GBA activity on GD neurons compared to WT was found, consistent with the minor GBA levels in GD neurons detected in the western blot. In TS, derived neurons were analyzed by immunofluorescence for Lamp2 (lysosome marker), observing an increase in size and number on the TS neurons in contrast to WT. Also, TS neurons were analyzed by transmission electron microscopy, presenting membranous lamellar bodies in the cytosol of TS.\n\t\t\t\t Both iPSC diseases have been used as a platform for testing therapeutical drugs efficiency on the iPSC derived neurons.
Author: Erika Lorenzo Vivas
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W92443335