HemaCare recently hosted a panel at the International Society of Cell Therapy’s annual meeting on Sourcing, Isolating, Preserving, Shipping and Tracking Biological samples. Previously, we summarized why cell quality is critical in developing cell therapy applications. The goal of cell therapy is to deliver cells to a patient to perform a function. Therefore maintaining the function of the cells is critical for developing cell therapies. At the HemaCare hosted panel, Dr. Stephen Minger (Scientific Advisory Board member of Hemacare and Chief Scientist at GE Healthcare Life Sciences) presented on how over the last 5 years, they have developed large scale amplification of cells for drug development and cell therapy applications. He summarized the challenges and solutions they have encountered in characterizing large scale lots of human cells.
The Goal: Produce highly functional industrial scale human cardiomyocytes
Creating the platform for large scale cell expansion and characterization has been an enormous endeavor. But GE Healthcare had an arsenal of resources and experience in regulating difficult processes, the rigor and attention to detail involved in creating jet engines can be applied to creating cell production processivity with the precision necessary for creating a repeatable, scalable protocol.
As Dr. Minger described: "With a protocol which is very similar to how we build jet engines in GE, by literally each day assessing the cells and standardizing the process all the way through. We generate human cardiomyocytes. We exhaustively characterize the cells."
Dr. Minger described the process they developed to create human cardiomyocytes to use in cardiotoxicity screening of new compounds prior to clinical trials. To reach their final goal of 5 x 109 cardiomyocytes, at any given point in time, they are actively growing 20 x 109 human embryonic stem cells. The cells proceed through a 28 day differentiation protocol resulting in 40 flasks of nearly solid contractile sheaths of myocardium beating in synchrony at 70 beats per minute.
How do they validate their cells?
To produce cells in such a massive scale is amazing, but the outstanding questions are clear – are they functional? The meticulously detailed protocol associated with these cells includes daily monitoring and exhaustive characterization along the way. Typical characterization involves phenotypic markers and quantification, largely reliant upon flow cytometry.
However, GE Healthcare Life sciences has turned to a more in depth analysis: high content imaging. The advent of high content imaging analysis permits in depth functional analysis alongside phenotypic data typically obtained via flow cytometry. Phenotype and intracellular data are collected as a static time point that can be reanalyzed as needed in the future. Multi-target data is generated which includes:
- Nuclear morphology
- Nuclear coordination
- Organelle distribution and shape
- Membrane potential
Through the meticulously monitored protocol highly functional cardiomyocytes for use in cardiotoxicity screening in drug development have been established.
Why the FDA is interested?
The rigorous nature of cell characterization performed by GE Healthcare Life Sciences has caught the attention of the US FDA. Dr Minger stated: "We’re in negotiations with the FDA to make this the standard test for how pharma should assess the potential cardiotoxicity of new compounds.”
Their platform is being validated for:
- Consistency in the process
- Controls in the process
- Analytic parameters
The value of the comprehensive data collected through high content imaging is critical in supporting and the use of cell platforms focused on clinical outcomes.
Dr. Minger also presented briefly on how they have expanded their standardized protocols to cell production for T cell therapies and CAR therapies. Creating high quality functional cells all begins with the highest quality source cells. As a prestigious member of our Scientific Advisory Board, Dr. Minger is helping HemaCare create the future of cell therapy applications.
Coming up, we share the highlights of Dr. Aby Mathew’s, yet another Scientific Advisory Board member of HemaCare, talk on biopreservation of samples and its role in cell therapy developments.