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Induced pluripotent stem cells as a tool for pharmacological and toxicological studies: a potential role of autophagy in sarcopenia

Grant number: 18/07633-2
Support type:Scholarships abroad - Research
Effective date (Start): April 01, 2019
Effective date (End): December 31, 2019
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal researcher:Claudia Bincoletto Trindade
Grantee:Claudia Bincoletto Trindade
Host: Rita Perlingeiro Kyba
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Research place: University of Minnesota (U of M), United States  


Induced Pluripotent Stem (iPS) cells emerge as a great promise for therapy in various diseases, such as ischemic heart failure, Parkinson's, Alzheimer's and Huntington's diseases, diabetes mellitus, sickle cell anemia, muscular dystrophy, among others. iPS are an unlimited source of cells with pluripotent potential, similar to those of embryonic stem cell (ESC), but with the advantage of being generated from human somatic cells, such as fibroblasts or blood cells, and not from embryos. In vitro studies of disease modeling with iPS cells have been prominent in the screening of new drugs and/or new pharmacological targets, since cells obtained from patients represent much better human diseases than the animal models. In addition, the development of alternative methods to animal use has been prominent in the scientific community and in ethics committees. Within this context, the first objective of this proposal is the training in methodologies involved the generation and derivation of human iPS from adult somatic cells. After obtaining and identifying of human iPS cells by transfection of specific transcriptional factors, the iPSs will be transduced with Pax3 or Pax7 to generate myogenic muscle cells and then myotubes. The next step of this proposal is the evaluation of the autophagy process in the homeostasis of these cells, using specific inducers and inhibitors of autophagy. The last step of this project is the development of an atrophy/cachexia/sarcopenia model, all events associated with loss of muscle mass under different pathophysiological conditions. We will study more precisely the possible autophagy protective role or not in muscle proteolysis, aiming at the search for molecular/cellular targets that can control this event. It is worth mentioning that studies aimed at modulating autophagy in human iPS cells is an innovative proposal that can be implemented in Brazil, thus enabling the continuity of this research within the Department of Pharmacology, EPM / UNIFESP.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ORTIZ-CORDERO, CAROLINA; BINCOLETTO, CLAUDIA; DHOKE, NEHA R.; SELVARAJ, SRIDHAR; MAGLI, ALESSANDRO; ZHOU, HAOWEN; KIM, DO-HYUNG; BANG, ANNE G.; PERLINGEIRO, RITA C. R. Defective autophagy and increased apoptosis contribute toward the pathogenesis of FKRP-associated muscular dystrophies. STEM CELL REPORTS, v. 16, n. 11, p. 2752-2767, NOV 9 2021. Web of Science Citations: 1.

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