Descripción del proyecto
Animar a los fagocitos autorrenovables a encontrar nuevas fuerzas para combatir las infecciones pulmonares
Los macrófagos, literalmente «grandes comedores», son un tipo de leucocitos que limpian el cuerpo de partículas no deseadas, lo que incluye patógenos y desechos celulares. Fomentan la homeostasis a través de la eliminación de microbios y células muertas y realizan funciones tróficas, reguladoras y de reparación. Los macrófagos autorrenovables residentes en los tejidos son una población heterogénea, y muchos de ellos no se han diferenciado en su identidad celular final. El entorno tisular parece desempeñar un papel fundamental en el fenotipo e influir en la expresión de los genes. El proyecto iPSC2Therapy, financiado con fondos europeos, está investigando la capacidad de integrar macrófagos alveolares encontrados en los pulmones en células madre pluripotentes inducidas para controlar su potencial regenerativo. El objetivo final es mejorar la reserva de macrófagos alveolares del cuerpo o intercambiarla por los integrados en células madre como tratamiento de las infecciones pulmonares micobacterianas.
Objetivo
Tissue resident macrophages (TRMs) can be found in various organs and fulfil important functions in host defence and tissue homeostasis. Recent studies in the murine system suggest profound tissue plasticity and self-renewal capacity of TRMs, rendering this cell population highly suitable for new cell-based therapies. Mycobacterial infections represent a serious health problem, for which new therapies are highly needed. Given the important role of alveolar macrophages (MΦs) in pulmonary host defence, I propose a cutting-edge MΦ based therapy using induced pluripotent stem cell (iPSC) technology. The unique features of iPSC will allow to investigate important regulators for the development and regenerative potential of human MΦs with the overall aim to apply these cells as an innovative treatment for pulmonary (non)tuberculous mycobacterial infections. I go beyond current knowledge and envision to enhance or exchange the endogenous alveolar MΦ cell pool by iPSC-MΦs, thereby introducing a completely new cell therapy concept. This ground-breaking cell transfer concept will have broad application potential to combat life threatening infectious diseases of the lower respiratory tract and may even be expanded to Mycobacterium tuberculosis infections. Using different knock-out iPSC lines, I will unravel important regulators for the regenerative potential of iPSC-MΦs following intra-pulmonary transfer. State-of the-art genome editing will be combined with innovative single cell RNAseq tools to understand and enhance the regenerative properties of human iPSC-MΦs. Using established cell depletion and cell transfer techniques, I will decipher the therapeutic potential of mature human iPSC-derived MΦ in vitro and in vivo using humanized mouse models and pre-clinical mycobacterial infections scenarios. The iPSC2Therapy proposal will provide an innovative anti-mycobacterial treatment with broad implications to infectious diseases and beyond.
Ámbito científico
- medical and health sciencesmedical biotechnologygenetic engineeringgene therapy
- medical and health scienceshealth sciencesinfectious diseases
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- natural sciencesbiological sciencesgeneticsgenomes
- medical and health sciencesbasic medicinephysiologyhomeostasis
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
30625 Hannover
Alemania