PanTHERA CryoSolutions sat down with Dr. Anna Jezierski to hear from her about her work and how our novel Ice Recrystallization Inhibitors are being used for iPSC-based research.
Dr. Anna Jezierski is a Research Officer with the Human Health Therapeutics Research Centre at the National Research Council of Canada and an Adjunct Professor at the Department of Biochemistry, Microbiology and Immunology at the University of Ottawa. Her research focus is on leveraging human induced pluripotent stem cells (iPSCs) to develop more predictive and translational models of the central nervous system (CNS). More specifically, the blood brain barrier (BBB) combining stem cells, organ-on-chip and 3D tissue bioprinting technologies. These models are routinely utilized to study the BBB permeability of CNS targeting biotherapeutics, neurotropic viruses and immunotherapies. A parallel research focus is to leverage iPSCs as a renewable and scalable cell source to generate immune cells, namely natural killer cells engineered to express chimeric antigen receptor (CAR), as novel sources of “off-the-shelf” immunotherapies targeting hematological malignancies and solid tumors.
Dr. Jezierski, thank you for sitting down with us today, could you tell us how you explain your work to people who don’t work in your field?
I am a stem cell biologist by training. I work primarily with human iPSCs whose discovery have enabled a breath of applications in regenerative medicine, immunotherapy, disease modeling, and drug discovery as they possess the unique ability to differentiate into any cell type found in the human body. iPSCs have become a critical tool in our CNS research, offering a scalable and reproducible platform to study various aspects of brain development and function. In addition, iPSCs derived from patients with neurological disorders and rare diseases enable the creation of disease models in vitro offering new insights into their underlying pathophysiology. This allows researchers to study disease mechanisms, identify disease-specific targets, screen potential therapeutics, and develop novel treatments. Lastly, iPSCs also hold the potential to revolutionize regenerative medicine and cancer therapy, as they can be coaxed into becoming replacement cells for damaged or diseased tissues and organs or engineered into unique immune cells with robust cancer fighting capabilities.
How do you think Ice Recrystallization Inhibitors (IRIs) play a role in your work?
It’s always exciting when novel technologies can improve the way we cryopreserve cells to improve the quality, integrity and reproducibility of our iPSC research platforms. This is essential for maintaining a consistent and renewable source of iPSC cell banks to enable the subsequent differentiation into specific cell types of interest. This is equally important for iPSC derived cell types, such as neurons, which are highly specialized cells of the CNS that are able to transmit chemo-electrical impulses. These mature neurons, which are costly and time-consuming to generate, are also highly susceptible to cryoinjury. Optimization of a cryopreservation process that can improve functional recovery post-thaw is key to accelerating research discovery and translation by ensuring an adequate supply of functional cells. Working collaboratively with the laboratory of Dr. Robert Ben at the University of Ottawa, we show that small molecule IRIs may be potent inhibitors of ice recrystallization-mediated cryoinjury in iPSC and iPSC-derived neurons improving post-thaw outcomes, such as increased viability, recovery and neuropharmacological responses. We illustrate how IRI technology can be a versatile and adaptable platform that can be incorporated in routine cryomedias to develop a customized and improved cryo-formulation for these specialized cell types.
What are some of the industries or some areas that you think that the IRIs can potentially be game changing for?
Cell-based cancer immunotherapies are quickly becoming novel treatment modalities owing to the recent successes of chimeric antigen receptor (CAR)-T cell therapies. Cryopreservation is a key enabling technology contributing to the overall success and accessibility of these innovative treatments to patients. The importance of cryopreservation has also been highlighted by the COVID-19 pandemic, emphasizing its necessity in establishing a reliable cold chain for the storage and distribution of vaccines. This is especially crucial for vaccines, like those utilizing mRNA technology, that require ultralow-temperature storage. Forward thinking, emerging methods in the cryopreservation of tissues and organs could potentially eliminate the extended waiting lists for organ transplantation if proven successful. Collectively, improving cryopreservation methods, such as IRI technology, will be key to developing an effective and efficiently managed cryo-chain to support the successful delivery of cell-based therapies (and other therapies) to patients.
What are some future studies that you foresee for the IRIs in your research?
It is very unlikely that there will be a universal, one-size-fits all cryopreservation solution for all cells – this will require a cell-dependent strategy that is scalable and able to support not just R&D efforts but also future biomanufacturing requirements. In fact, optimizing cryopreservation early in the preclinical drug discovery pipeline is a strategic and practical approach that contributes to the overall success of translational medicine. It enhances the efficiency, reliability, and translatability of research efforts, laying the groundwork for successful clinical applications. Our study was the first to assess a panel of IRIs developed by the Ben laboratory in iPSCs and iPSC-derived neurons. This seminal proof-of-concept study now paves the way for testing the utility of the IRIs in multiple iPSC-derived cell types and at various stages of differentiation to further elucidate their effectiveness as cryoprotectants.
This conversation has been edited for brevity and clarity.
About PanTHERA CryoSolutions
PanTHERA CryoSolutions is a Canadian corporation that designs and manufactures cryopreservation solutions for cells, tissues and organs for research and clinical markets. Our patented ice recrystallization inhibitor (IRI) technology exceeds other products by providing superior cryopreservation and increasing post-thaw cell recovery and function for our customers. The technology enables the use of significantly less costly storage and transportation systems limiting the need for liquid nitrogen use for some cell therapy applications