| Grant number: | 12/50880-4 |
| Support Opportunities: | Research Projects - Thematic Grants |
| Start date: | December 01, 2012 |
| End date: | February 28, 2019 |
| Field of knowledge: | Biological Sciences - Biophysics - Cellular Biophysics |
| Principal Investigator: | Alexander Henning Ulrich |
| Grantee: | Alexander Henning Ulrich |
| Host Institution: | Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Pesquisadores principais: | Luiz Roberto Giorgetti de Britto ; Marimélia Aparecida Porcionatto |
| Associated scholarship(s): | 18/03607-7 - Culture and differentiation of dopaminergic neurons from embryonic stem cells,
BP.TT 18/05543-6 - GABAergic neurons differentiation from mouse embryonic stem cells, BP.TT 17/17972-6 - Silencing of CaMKII-alpha in a hippocampal cell line as an in vitro model for the immature dentate gyrus neuropsychiatric endophenotype, BP.IC + associated scholarships - associated scholarships |
Abstract
Stem cells (SC) are unspecialized cells withself renewal capacity and with the ability to originate different cell types | of the body. In recent years, SC nave emerged as a significant therapeutic promise for several diseases. Furthermore, cancer stem cells (CSC ) have been implicated in initiation and growth of tumors, resistance to conventional therapies and, consequently, in recurrence of the disease, becoming a potential target for therapy. The basic structure of a SC depends on its genetic constitution, however the determination of a specific phenotype also depends on cell exposure to intrinsic and extrinsic factors in their microenvironment. Our laboratory has been studying the role of bradykinin (BK) and purines in induction, progression and phenotype determination in neural differentiation of different types of SC. As one of the main findings of our group, BK increased neurogenesis in several models of SC and also showed a neuroprotective effect, reversing the induction of apoptosis. Based on these data, in this project, we propose to study the interrelationship between purinergic and kininergic systems as a target for therapies using SC. For this purpose, we will evaluate the effect of BK and its stable analogs as potential tools for cell therapy in a preclinical model of Parkinson's disease, together with neural stem cell transplantation. Somatic cells of Parkinson's disease patients will be reprogrammed to pluripotent cells (iPS) to study possible alterations in the kininergic and purinergic systems and in their effects on the modulation of neural differentiation. We will develop DNA aptamers in order to obtain specific markers for different types of SC, such as mesenchymal and cancer SC. These aptamers have possible therapeutic applications, in the purification of mesenchymal SC for cell therapy and, in the case of tumor SC, have a diagnostic value in detection of those cells in biological fluids. To define new therapeutic targets and regarding the anti-proliferative effect of BK on neural stem cells (NSC), we will study the expression of kinin system and the involvement of their receptors on tumor progression in cells derived from lung tumors and glioblastoma with high malignancy. Furthermore, we will study P2X7 receptor in a mouse model of epilepsy, providing a second pre-clinical model in addition to the rat model for Parkinson's disease. (AU)
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MÉTODO DE IDENTIFICAÇÃO DE COMPOSTOS INIBIDORES DE ECTO-5`-NUCLEOTIDASE HUMANA (CD73) E USO DOS COMPOSTOS IDENTIFICADOS BR1020180071661 - Universidade de São Paulo (USP) . ANTONIA TAVARES DO AMARAL / ALEXANDER HENNING ULRICH / ARQUIMEDES CHEFFER / LUCAS GASPARELLO VIVIANI - April 2018, 09