Periodic Reporting for period 1 - HD-Neu-Screen (HD-MEA-based Neuronal Assays and Network Analysis for Phenotypic Drug Screenings)
Periodo di rendicontazione: 2020-01-01 al 2021-06-30
The central aim of this proof-of-concept (PoC) project was to develop functional neuronal assays for characterizing disease models and screening of compounds aimed at treating diseases of the central nervous system. Induced-pluripotent-stem-cell (iPSC) technology enables scientists to have unlimited access to human cells that hold the potential to recapitulate diseases in vitro and that can be used for compound testing. We combined iPSC and high-density-microelectrode-array (HD-MEA) technologies. HD-MEA technology offers unprecedented temporal and spatial resolution and enables to record spontaneous and stimulated electrical activity of neuronal preparations across scales, from subcellular compartments through single neurons to entire neuronal networks over days and months. HD-MEAs were initially developed in a single-well format and have been commercialized as single- and multi-well formats by the spin-off company MaxWell Biosystems AG (http://www.mxwbio.com(si apre in una nuova finestra)).
This ERC PoC was focused on developing and optimizing experimental procedures and the data analysis pipeline for phenotyping human iPSC-derived neurons and screening of the effects of neuroactive compounds. The different activities included (1) the optimization of the culturing protocols of human iPSC-derived neurons on HD-MEAs, and (2) the development of algorithms for feature extraction at subcellular, single-neuron and networks levels. We then used the extracted features to (3) characterize healthy and diseased neurons, (4) evaluate drug effects, and (5) to classify cell types.
The scientific work was accompanied by an assessment of the potential market landscape, and the establishment of relevant collaborations and partnerships to enter the drug screening market. The PoC project, the proposed culturing strategies, and data analysis pipeline were developed in collaboration with the spin-off company MaxWell Biosystems AG and will serve as a basis for MaxWell to develop projects with customers from the pharmaceutical industry. In particular, the developed metrics and data-analysis strategies will allow MaxWell Biosystems to serve industry needs in the field of assessment of drug effects at higher throughput.
An important aspect of this project included that we used human iPSC-derived cell models, which eliminates ethical issues related to the use of animals or human embryonic stem cells in medical research. Human iPSC-derived cell models have been demonstrated to faithfully recapitulate pathology aspects and to provide better predictivity than currently used animal models and immortalized cell lines.
This ERC PoC was focused on developing and optimizing experimental procedures and the data analysis pipeline for phenotyping human iPSC-derived neurons and screening of the effects of neuroactive compounds. The different activities included (1) the optimization of the culturing protocols of human iPSC-derived neurons on HD-MEAs, and (2) the development of algorithms for feature extraction at subcellular, single-neuron and networks levels. We then used the extracted features to (3) characterize healthy and diseased neurons, (4) evaluate drug effects, and (5) to classify cell types.
The scientific work was accompanied by an assessment of the potential market landscape, and the establishment of relevant collaborations and partnerships to enter the drug screening market. The PoC project, the proposed culturing strategies, and data analysis pipeline were developed in collaboration with the spin-off company MaxWell Biosystems AG and will serve as a basis for MaxWell to develop projects with customers from the pharmaceutical industry. In particular, the developed metrics and data-analysis strategies will allow MaxWell Biosystems to serve industry needs in the field of assessment of drug effects at higher throughput.
An important aspect of this project included that we used human iPSC-derived cell models, which eliminates ethical issues related to the use of animals or human embryonic stem cells in medical research. Human iPSC-derived cell models have been demonstrated to faithfully recapitulate pathology aspects and to provide better predictivity than currently used animal models and immortalized cell lines.