Developing stem cell therapies: expansion strategies and lessons learned

The field of mesenchymal stem/stromal cell (MSC) therapy for critically ill patients has been evolving rapidly since the emergence of preclinical studies on the beneficial effect of MSCs in improving survival and organ functions of septic animal models. Results of a Phase 1, dose-escalation safety trial recently completed by Research scientists from Ottawa Hospital Research Institute (OHRI) suggest that MSCs are safe and well tolerated in patients with septic shock. The OHRI team is now pursuing a Phase II randomized controlled trial to continue the safety evaluation and look for signs of efficacy.

In this webinar, OHRI Investigator Dr. Shirley Mei and Senior Scientist Dr. Lauralyn McIntyre will discuss how their team translated a MSC therapy manufacturing process from the preclinical laboratory to a GMP setting, and what considerations were taken to design a first in human trial to examine MSCs for the treatment of septic shock. Corning Field Applications Scientist Dr. Catherine Siler will present tools and process design strategies for achieving consistent and efficient expansion of therapeutic cells, including scale-up and scale-out options and closed system designs.

• Challenges in developing a cell therapy product for acutely ill patients      
• Trial design consideration for assessing safety of MSC therapy in septic shock       
• Lessons learned from cell therapy products used in our early phase trial      
• Process design for consistent and efficient scale up of therapeutic cells

Shirley Mei, PhD, MSc

Investigator, OHRI

Dr. Mei has 16 years of experience on the nonclinical development and translation of mesenchymal stem cell (MSC) therapy to clinic for critical illness without treatment. As a translational scientist, she has been working with ICU clinicians to conduct the worlds’ first-in-human clinical trial for septic shock patients with allogeneic MSC derived from bone marrow (NCT02421484), with plans to start a larger Phase II multi-centre efficacy trial. With a focus on bringing discoveries from the bench to the bedside, her current research includes studying how MSCs exert their immunomodulatory effect on immune cells using in vitro culture systems, preclinical disease models and clinical samples; and developing novel molecular strategies to enhance the benefit of cellular therapeutics. Her lab also conducts essential translational research, including the development of GMP-compliant cellular therapeutic products.

Lauralyn McIntyre, MD, MHSc, FRCPC

Senior Scientist, OHRI

Dr. Lauralyn McIntyre is an Intensivist at the Ottawa Hospital, Associate Professor in the Department of Medicine, University of Ottawa and a Senior Scientist with the Clinical Epidemiology Department of the Ottawa Hospital Research Institute. She is the Critical Care Research Director at the Ottawa Hospital and a member of the Canadian Critical Care Trials and Translational Biology Groups. Dr. McIntyre’s research programs focus on resuscitation, transfusion, and stem cell use in the critically ill. She has conducted observational studies, surveys, meta-analyses, and clinical trials that examine fluid resuscitation in the septic shock setting as well as the use of red blood cells, fresh frozen plasma, and transfusion alternatives in the critically ill. She is the lead investigator on a program of research that examines the use of mesenchymal stem cells for the treatment of septic shock (Cellular Immunotherapy in Septic Shock: CISS) and has received funding from the Stem Cell Network, the Ontario Institute for Regenerative Medicine and CIHR to conduct a phase II multicenter double blind RCT to examine safety and surrogate measures of efficacy in this highly vulnerable patient population.

Catherine Siler, PhD

Field Applications Scientist, Corning Life Sciences 

Dr Catherine Siler is an accomplished Field Application Scientist for Corning Life Sciences, with a PhD in Biology from Johns Hopkins University. Dr. Siler enables scientists and researchers in the life science industry to overcome challenges with cell culture and scale-up for clinical manufacturing of advanced therapies, and utilizes her research and teaching experience to drive the adoption of an industry-leading global product portfolio of innovative single-use consumables for research, process development and bioprocessing applications.