Axol & Metrion Interactive Stem Cell Forum

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Wednesday 23 May
9:00 am - 5:00 pm
Granta Centre, Granta Park

Stem Cell Event

Hosted by Axol Bioscience & Metrion Biosciences

Axol Bioscience and Metrion Biosciences will be holding a joint stem cell themed event on May 23 rd . The meeting will consist of presentations in the morning and afternoon demonstrations in Metrion Laboratories .

Axol & Metrion stem cell event

This is a free event. Lunch and refreshments are included.

Location

Granta Park:

The Abington Room
Granta Center

Programme

Forum Agenda

Find the agenda below. Early registration is advised due to limited spaces.

08:30 - 09:00 Arrival & Registration
09:00 - 09:05 Introduction & Welcome
09:05 - 09:35 Genetically Encoded Tools to Augment iPS-Cardiomyocyte Phenotyping ( 1 ) Dr Matthew Daniels | University of Oxford
Academic Consultant Cardiologist (Structural and Inherited heart disease) & PI
09:35 - 09:55 Utility of human iPSC-derived cardiomyocytes for pre-clinical safety assays and disease modelling ( 2 ) Dr Sarah Williams | Metrion Biosciences
Senior Scientist
09:55 - 10:25 Investigating the pathophysiology of Amyotrophic Lateral Sclerosis (ALS) using human induced pluripotent stem cell technology ( 3 ) Dr Gareth Miles | Univeristy of St Andrews
Senior Lecturer and Reader
10:25 - 11:00 Coffee
11:00 - 11:20 Human iPSC-derived microglia: immune cells of the brain ( 4 ) Dr Zoe Nilsson | Axol Bioscience
Product Manager
11:20 - 11:50 Tissue engineering approaches to modelling Alzheimer’s disease ( 5 ) Dr Eric Hill | Aston University
Programme Director for MSc Stem cells and Regenerative medicine
11:50 - 12:20 Subtype-specific optical action potential recordings in human iPS cell-derived cardiomyocytes for disease modelling and drug evaluation ( 6 ) Dr Daniel Sinnecker | Technical University of Munich
Clinical Cardiologist / Research Scientist
12:20 - 13:30 Lunch
13:30 - 17:00 Laboratory Demonstrations
17:00 - 17:15 Closing Remarks

Space is limited

Reserve your spot

Registrations will be confirmed and the organisers reserve the right to decline attendees.


1. Unfortunately it appears that the chemical dyes that have been a backbone of studies in neurons and cardiomyocytes are directly harmful. Genetically encoded indicators don't have this problem, and I will discuss our efforts to put them in interesting places within the cell to tell us things we never knew before.

2. At Metrion, human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) are being utilised as model systems for improving preclinical safety screening (CiPA initiative) and modelling human disease. We believe that to allow full integration of commercial iPSC-CM as models of human cardiomyocytes, their electrophysiological properties should be characterised using gold-standard techniques. Today, I will discuss how manual patch clamp techniques have been used to investigate the action potential characteristics and physiology of two iPSC-CM cell lines from Axol Biosciences. General firing properties were initially investigated, followed by the use of a variety of pharmacological tools to enable us to profile both ventricular and atrial lines. Extensive cell line characterisation such as this allows Metrion to provide fully validated assays utilising iPSC-CM.

3. Amyotrophic Lateral Sclerosis (ALS) is a devastating, fatal condition, which involves progressive paralysis due to loss of motor neurons (MNs) within the brain and spinal cord. There is a desperate need for new treatments to improve MN function and prevent MN loss in ALS. However, the development of new treatments requires a greater understanding of how and why MNs degenerate in the disease. A growing body of evidence implicates astrocytes as important non-cell autonomous contributors to ALS pathogenesis. We have therefore investigated the interactions between astrocytes and MNs in a completely humanised model of ALS, using human induced pluripotent stem cell (iPSC)-based technology. We have shown in co-culture experiments that astrocytes derived from iPSCs of ALS patients induce dysfunction in MNs derived from iPSCs of healthy individuals. The pathophysiological changes induced in control MNs by mutant astrocytes include a decrease in action potential output (hypoexcitability) due to loss of voltage-activated currents. Notably, the selective excision of ALS-causing mutations from astrocytes through CRISPR/Cas-9 reverses these phenotypes, confirming that the ALS mutation is responsible for non-cell autonomous MN pathophysiology. These findings implicate astrocyte-neuron signalling as an important potential target for novel ALS therapeutics.

4. Microglia are innate immune cells within the CNS, they act to regulate brain development and have key roles in neurogenesis, synaptic plasticity, repairing tissue injuries and immunity. More recently, the over-activation of microglia, leading to enhanced neuroinflammation, has been suggested to play a critical role in neurodegenerative disorders such as Alzheimer’s disease, ALS and Parkinson’s disease. Consequently, there is a need to study microglia in vitro to improve our understanding of their function and implication in disease progression. Axol’s innovation lab has developed human iPSC-derived microglia as a co-culture with human iPSC-derived cortical neurons, enabling research of the interaction between neurons and microglia, and as a mono-culture, allowing for investigations into microglia alone. This presentation will discuss the phenotypic and functional characterisation of these cells and describe how they can be used as a representative and translatable model for studying microglia in vitro in order to progress microglia targeted drug-discovery.

5. Alzheimer's Disease (AD) affects more than 35 million people worldwide. Neurons derived from induced pluripotent stem cell (iPSC) may enable Alzheimer's to be modelled in vitro. We have recently shown that membranes containing microscopic holes allow these brains cells to contact each other across the membrane, but do not allow the whole cell to pass through. This will allow us to grow diseased tissue in close proximity to healthy tissue in order to monitor the spread of disease. We have also shown that neurons derived from iPSC demonstrate electrical activity thus demonstrating the potential of the assay to track degradation in communication between cells. This model can be used to model disease progression, increasing our understanding of AD and facilitating the development and screening of new drugs and treatments.

6. Human induced pluripotent stem cells hold a great potential for research in the field of cardiac channelopathies. The talk will discuss how these cells can be used for disease modelling, as a safety pharmacology platform to assess the proarrhythmic potential of drug candidates, and for developing personalized therapeutic strategies. All these applications are challenged by the fact that iPSC-CMs generated by current differentiation protocols represent a mixture of cells with ventricular-, atrial-, and nodal-like phenotypes rather than a homogenous population of cells. A method is presented to optically record action potentials specifically from ventricular-, atrial- or nodal-like iPSC-CMs. This is achieved by lentiviral transduction with a construct in which a genetically-encoded voltage indicator is under the control of a subtype-specific promoter element. When iPSC-CMs are transduced with this construct, the voltage sensor is expressed exclusively in the cardiomyocyte subtype of interest, enabling subtype-specific optical membrane potential recordings using time-lapse fluorescence microscopy.


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