Title : Stem cell-derived models for studying human disease mechanisms and therapeutic interventions
Abstract:
Congenital diseases often present defects in multiple tissue and organs and require complex clinical care and in some cases surgical intervention. The use of autologous mesenchymal stem cells and patient derived cells from Induced Pluripotent Stem Cells (iPSCs) can allow one to study different aspects of birth defects in different affected tissues that may require different therapeutic solutions. These cells might also be valuable for the repair of tissue damage caused by disease or injury. The possibility of stimulating effective tissue repair or of engineering tissues for grafting with properties similar to native ones has indeed generated extensive interest over the years. The use of stem cells, and particularly autologous ones, still presents several challenges, particularly given the often limited information on the mechanisms leading to the disease, and issues with achieving consistent differentiation and with scaling up the generation of tissues in vitro.
She will discuss the value of different sources of patient-derived cells (e.g. iPSCs and mesenchymal stem cells, MSCs) for therapeutic development and approaches to disease modelling using as examples our work on diseases such as microtia, acrodysostosis and Duchenne Muscular Dystrophy (DMD), with a focus on cartilage and neural tissues, and highlight advantages and disadvantages of different models.
Her work on cartilage has indicated that all of the progenitor/stem cells we have studied differentiate more efficiently into cartilage when they are allowed to self-organize as spheroids than when encased in the different scaffolds we tested. At least in the case of microtia, spheroids mimic aspects of the disease that are not readily apparent in 2D (2-dimensional) culture. Furthermore, the organoids may provide a good model for studying skeletal growth defects in other diseases, such as acrodysostosis. On the neural tissue front, I will highlight the impact of culture cytoarchitecture also on hNSC (Human Neural Stem Cell) phenotype and damage response. Our studies have indicated that 3D (3-dimensional) models in hydrogels may be better predictors of human in vivo response to damage and compound toxicity than 2D cultures, hence could provide a simpler and higher throughput system than brain organoids for initial drug screenings. On the other hand, important information on the molecular basis of disease can be facilitated by simpler models, and this has led to the identification of cell-autonomous defects in DMD astrocytes and their potential role in the neural pathology of the disease.
