APR 15, 2021 8:00 AM PDT

Human Pluripotent Stem Cells as a Model for Neurodevelopmental Toxicity

Speaker
  • Post Doctoral Research Fellow
    Biography

      Cláudia Miranda is currently a Post Doctoral Research Fellow at iBB – Institute for Bioengineering and Biosciences/ Associate Laboratory i4HB - Institute for Health and Bioeconomy/ Instituto Superior Técnico. The main focus of her research is the development of a scalable and cost-effective culture platforms for expansion of human pluripotent stem cells and their controlled differentiation into different lineages for drug discovery and toxicity assessment. After finishing a Degree in Biochemistry, she received a MSc. in Biotechnology and a Ph.D. in Biotechnology and Biosciences at Instituto Superior Técnico, University of Lisbon, focusing on the 3D culture and neural induction of human pluripotent stem cells.


    Abstract

    Date:  April 15, 2021

    Time: 8:00am PDT, 11:00am EDT

     

    Stem cell’s unique properties confer them a multitude of potential applications in the fields of cellular therapy, disease modelling and drug screening fields. In particular, the ability to differentiate neural progenitors (NP) from human induced pluripotent stem cells (hiPSCs) using chemically-defined conditions provides an opportunity to create a simple and straightforward culture platform for application in these fields. Here, we demonstrated that hiPSCs can undergo neural commitment inside microwells, forming characteristic neural structures resembling neural rosettes and further give rise to glial and neuronal cells. Furthermore, this platform can be applied towards the study of the effect of neurotoxic molecules that impair normal embryonic development. As a proof of concept, the neural teratogenic potential of the antiepileptic drug valproic acid (VPA) was analyzed. It was verified that exposure to VPA, close to typical dosage values (0.3 to 0.75 mM), led to a prevalence of NP structures over neuronal differentiation. Since prenatal exposure to cannabis has been associated with an altered rate of mental development and significant changes in nervous system functioning, we also investigated the effect of continuous exposure to cannabinoids – cannabidiol, Δ9-THC, and two synthetic cannabinoids (SC) - on developing human neurons, mimicking the prenatal exposure by drug-consuming mothers. In sum, all studied substances have a profound impact on the developing neurons, highlighting the importance of thorough research on the impact of prenatal exposure to natural and SCs.

     

    Learning objectives:

    • Discuss and understand the use of three-dimensional microwells to generate human pluripotent stem cell-derived neural spheroid cell models.
    • Establish a neurodevelopmental model of prenatal exposure to valproic acid and cannabinoids.
    • Use microwells as a platform to analyze the effects of drug exposure during neural development.

     

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