1 May, 2020

GIVIMP Protocol to Differentiate Cells (Preclinical Studies)

THE FIRST CREATIO’S GIVIMP-COMPATIBLE PROTOCOL TO DIFFERENTIATE PLURIPOTENT STEM CELLS INTO FUNCTIONAL NEURONS

In this new publication, Creatio’s scientists led by Dr Comella-Bolla have performed an in-depth characterization of an in vitro differentiation protocol that produces functional forebrain neurons, including medium spiny neurons, from human Pluripotent Stem Cells (hPSCs) in just 37 days.

In the article published now in Molecular Neurobiology, Comella and colleagues precisely describe the different phases of the differentiation and the cocktails of molecules used to induce neuronal differentiation by controlling neural induction, regionalization, neurogenesis and synaptogenesis. The differentiation process has been characterized using a combination of high-cell content analysis, high-throughput quantitative gene profiling with the Openarray platform and functional calcium imaging (high-throughput calcium imaging). Creatio’s protocol reproduces the dynamic changes in gene expression that occur during human neurodevelopment. Functional phenotype of obtained neurons is confirmed by the expression of synaptic markers, voltage-gated ion channels and neurotransmitter receptors while diverse spontaneous activity patterns are displayed.

Considering all these characteristics, we believe that this protocol is an ideal platform for the in vitro study of both neurodevelopment and neuronal diseases through the newly created platform AVANTDRUG®.

Importantly, Creatio’s protocol has been developed and validated following the strict guidelines set by the ISO9001 and the OECD in the Guidance Document on Good In Vitro Method Practices (GIVIMP). This guidance document was generated to set an international regulatory context following the recent increase in availability of in vitro test methods for evaluating chemical safety. The GIVIMP guidelines define standards for the test methods and conditions under which data are generated to ensure that resulting data are rigorous and reproducible with as its final aim fostering confidence in in vitro alternatives to animal testing. The protocol developed by Creatio is ideal for its use as a drug screening and neurodevelopmental toxicology platform.

The article also includes animal transplantation experiments which demonstrate that the transplanted cells survive within the host, finish differentiation and successfully integrate into the endogenous circuitry without forming teratoma, making the protocol compatible with cell therapy-based approaches for neurodegenerative diseases like Huntington’s disease.