Stem Cell Biology

Summary of research

Induced pluripotent stem cell (iPSC) technology gives the opportunity to generate early stem cells from somatic cell types (incl. skin, hair, blood), and to generate patient-derived and disease-specific neural cell types of interest. This discovery opened new avenues to model diseases, where the genetic components have yet to be identified, or for which animal models are inappropriate. We use up-to-date and optimized procedures to generate patient iPSCs and iPSC-derived astrocytes, oligodendrocytes, microglia and neurons as well as brain organoids. The cultures are functionally analyzed in collaboration with on-side laboratories with state-of-the-art expertise in advanced microscopy, electrophysiology, proteomics and high content cellular screening. These efforts created the base for the VU/VUmc iPSCenter (www.ipscenter.nl) with the goal to improve current and to develop new treatment options for a variety of brain disorders. iPSC technology hold great promises for high-throughput screening platforms and cell replacement therapies for the future.

Our goal is to identify and describe glial defects in neurodevelopmental disorders, and to perform proof-of-concept studies for glial-targeted therapy strategies using advanced stem cell technologies. Although a glial component in neurological disorders is increasingly appreciated, we still lack proper understanding of neuron-glia communications. Current projects involve generation and analysis of iPSCs from patients with the neurodevelopmental disorders Rett Syndrome, Tuberous Sclerosis Complex and Schizophrenia, and the leukodystrophies Vanishing White Matter, 4H leukodystrophy and adrenoleukodystrophy. In collaboration we develop new iPSC-based model systems to study e.g. myelination processes and Tau pathology in humans

More about our work can also be found on our website.

Team leader

Vivi Heine, MD PhD

Dr. Vivi Heine is Associate Professor of Child and Youth Psychiatry at the Emma Children’s Hospital, Amsterdam UMC, Amsterdam Neuroscience.

Team members

Stephanie Dooves
Postdoctoral Resesarcher

Karen Laupman
PhD Student

Lauria Claeys
PhD student

Lucia Castillo Ransanz
PhD Student

Roberto Montoro Ferrer
PhD Student

Nicki Covena
PhD Student

Kevin Batenburg
PhD student

Amber Mater
Technician

Nicole Breeuwsma
Technician

Liza Kok
Technician

Publications

• Multi-level characterization of balanced inhibitory-excitatory cortical neuron network derived from human pluripotent stem cells
  Abstract Generation of neuronal cultures from induced pluripotent stem cells…   »
• Affected astrocytes in the spinal cord of the leukodystrophy vanishing white matter
  Abstract Leukodystrophies are often devastating diseases, presented with progressive clinical…   »
• Patterning factors during neural progenitor induction determine regional identity and differentiation potential in vitro
  Abstract The neural tube consists of neural progenitors (NPs) that…   »
• Generation of Isogenic Controls for In Vitro Disease Modelling of X-Chromosomal Disorders
  Abstract Generation of proper controls is crucial in induced pluripotent…   »
• Neuron-Glia Interactions Increase Neuronal Phenotypes in Tuberous Sclerosis Complex Patient iPSC-Derived Models
  Abstract Tuberous sclerosis complex (TSC) is a rare neurodevelopmental disorder…   »

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Funding

2022-2025 NWO TTW grant on multi-organ platform for body barriers, in collaboration with Prof. de Vries, Prof. Gibbs and Prof Feilzer 

2021-2025 ENW Open grant on 3D cell-instructive engineered stem cell models of human brain networks, in collaboration with Dr. A Accardo (TU Delft) 

2020-2023 Coordinator of ERA-Net for Research Programmes on Rare Diseases “NG4Leuko”