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PRECLINICAL CORES

Human Neuron Core
Robin Kleiman, PhD and Mustafa Sahin, MD, PhD, Co-Director  

 

The Human Neuron Core at Boston Children’s Hospital offers a new paradigm for disease modeling and preclinical drug screening informed by broad expertise at Harvard in neuroscience, neurology and stem cell biology. Generous funding from the Massachusetts Life Sciences Center has enabled us to significantly expand our equipment and services and open them to the broader research community.

This core will exploit transformative stem cell technology for both modeling of specific diseases and screening of test compounds in human neurons derived from induced pluripotent stem cells (iPSCs). The goals of this service are to: (1) develop standard operating procedures for the generation of different types of neuronal cell lines; (2) create neuronal cell lines from iPSCs derived from patients with specific diseases and from healthy controls; (3) compare key characteristics (e.g. shape, growth, synaptic connectivity, protein composition) of patient-derived and control-derived neurons; (4) identify disease-specific characteristics in patient-derived neurons; (5) screen drug candidates in disease-specific cell lines to greatly increase the speed and specificity of drug discovery; and (6) compare results of these “pre-clinical” drug trials with clinical trials in patients.
Services fall in three main categories 

  • The Human Neuron Differentiation Service provides well-characterized human neurons to academic investigators and industry collaborators to support translational research programs. Cell types available include human neurons derived from induced pluripotent stem cell (iPSC) lines, including excitatory cortical neurons, GABA neurons, motor neurons, dopaminergic neurons and sensory neurons.
  • The Human Neuron Phenotyping Service can compare key cellular characteristics across patient-derived and control-derived neurons. Phenotyping services include use of high content measures of neuronal morphology, neuronal excitability using multiple electrode array recordings and targeted RNA sequencing profiles (AmpliSeq) of neuronal transcriptomes.
  • The expanded Assay Development Screening Facility provides multiple live-cell screening platforms that can assess image- and activity-based measures of live neurons hourly, in a medium/high-throughput capacity. Key equipment available for hourly use includes the Hamamatsu Functional Drug Screening System, the ArrayScan XTI: High content screening with live cell imaging and a range of robotics and liquid handlers to support drug screening.

 

 

 

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