SECRET - Evaluation of the neuro-protective properties of perinatal derivatives using murine iPSC-derived neurospheroids. (SECRET)

Perinatal tissues encompass a large and diverse cell/tissue family obtained from term pregnancies. Perinatal derivatives (PnDs) include amniotic membrane, chorion, Wharton's jelly, amniotic fluid, and the cells isolated from these tissues, as well as the factors that these cells release. PnD have drawn much attention due to their immune-modulatory and tissue-protecting properties, making them attractive candidates in regenerative medicine. Focussing on neuro-protection, we will here investigate whether different types of PnDs are able to inferfere with inflammation-associated neuro-degenerative processes in murine induced pluripotent stem cell (iPSC)-derived neurospheroids. Neurospheroids cultured from iPSC represent an important research tool to study neuron-astrocyte interactions, during development, homeostasis and stress. Hereto, we developed a 5-week old murine iPSC-derived neurospheroid model containing mature neurons and astrocytes in order to evaluate the therapeutic potential of several neuro-protective/modulating compounds in vitro preceding animal experiments. Following development and characterization of this new murine iPSC-derived neurospheroid model, its sensitivity to immune signal-induced stress (a.o. stimulation with IL1b, TNF and/or LPS) has been demonstrated by monitoring astrocyte activation (a.o. production of IL6 and CXCL10). In this new project in collaboration with the 'Universita Cattolica del Sacre Cuore' (Rome, Prof. Ornella Parolini) and the 'Centro di Ricerca E. Menni' (Brescia, Dr. Antonietta Silini), we will now investigate the neuro-protective/modulating activity different PnDs on astrocyte activation in murine iPSC-derived neurospheroids. These studies will then allow to preselect the most potential PnDs for subsequent animal studies and/or human clinical trials in the field of neuro-degenerative disease.

Keywords:ORGANOID, IMMUNOMODULATION, STEM CELLS

Disciplines:Immunomodulation therapy