Deciphering the cellular crosstalk in the bone marrow microenvironment of acquired aplastic anemia towards the expansion of transplantable hematopoietic stem/progenitor cells
• Cláudia Lobato da Silva, Professor @ IST/ULisboa, PT
• Domingos Henrique, Principal Investigator @ iMM – Instituto de Medicina Molecular João Lobo Antunes, Lista, PT
• Doctor Joana Santos, Centro Hospitalar de Setúbal, EPE
• Doctor Luciana Leite, Centro Clínico da Guarda Nacional Republicana
• Professor Majlinda Lako, Institute of Genetic Medicine, Newcastle University
The aim of this project is to better understand the physiopathology of idiopathic aplastic anemia (AA) in what regards the cellular crosstalk in the bone marrow (BM) microenvironment, particularly focusing on hematopoietic stem/progenitor cells (HSPC) and mesenchymal stromal cells (MSC) towards the expansion of transplantable HSPC for autologous hematopoietic transplantation.
Adult HSPC and MSC from AA patients and healthy donors are isolated, cultured and thorough characterized. Since AA is a rare disease, in order to overcome the scarcity of cell samples, human induced pluripotent stem cell (hiPSCs) derived from AA patients (AA-hiPSCs) (gently provided by Professor Majlinda Lako from Institute of Genetic Medicine, Newcastle University, UK) are being used to be differentiated into HSPC and MSC. A co-culture model of HSPC-MSC, based on a BM biomimetic scaffold, will be established to study the cellular crosstalk between these cells. Culture conditions will be modulated by using specific molecules e.g., PPAR pathway modulators; arsenic trioxide) in order to assess the adipogenic differentiation bias observed in different studies for AA cells over healthy donor cells and its impact on the hematopoietic supportive capacity of these cells. Finally, HSPC will then be expanded ex vivo under previously optimized culture conditions and their engraftment potential and multilineage hematopoietic reconstitution capacity will be tested in vivo using an animal model (NSG mice) available at iMM.
DOCTORAL PROGRAM (36 ECTS)
• General Doctoral Training (6 ECTS)
• Bioentrepreneurship (6 ECTS)
• Biotecnologia Molecular (6 ECTS)
• Engenharia de Células Estaminais (6 ECTS)
• Advanced Experimental Techniques and methodologies ()
• Formação Doutoral Geral ()