Donor Variability in Growth Kinetics of Healthy hMSCs Using Manual Processing: Considerations for Manufacture of Cell Therapies. Issue 2 (25th January 2018)

• Record Type: Journal Article
• Authors: Detela, Giulia; Bain, Owen W.; Kim, Hae‐Won; Williams, David J.; Mason, Chris; Mathur, Anthony; Wall, Ivan B.
• Is Part Of: Biotechnology journal. Volume 13:Issue 2(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-01-25
• Subjects: autologous cell therapies -- bioprocess design -- expansion potential -- human mesenchymal stromal cells (hMSCs) -- variability; Biotechnology -- Periodicals; 660.605
• DOI: 10.1002/biot.201700085
• Languages: English
• ISSNs: 1860-6768

Abstract

Abstract : Human mesenchymal stromal cells (hMSCs) are excellent candidates for cell therapy but their expansion to desired clinical quantities can be compromised by ex vivo processing, due to differences between donor material and process variation. The aim of this article is to characterize growth kinetics of healthy baseline "reference" hMSCs using typical manual processing. Bone‐marrow derived hMSCs from ten donors are isolated based on plastic adherence, expanded, and analyzed for their growth kinetics until passage 4. Results indicate that hMSC density decreases with overall time in culture ( p < 0.001) but no significant differences are observed between successive passages after passage 1. In addition, fold increase in cell number dropped between passage 1 and 2 for three batches, which correlated to lower performance in total fold increase and expansion potential of these batches, suggesting that proliferative ability of hMSCs can be predicted at an early stage. An indicative bounded operating window is determined between passage 1 and 3 (PDL < 10), despite the high inter‐donor variability present under standardized hMSC expansion conditions used. hMSC growth profile analysis will be of benefit to cell therapy manufacturing as a tool to predict culture performance and attainment of clinically‐relevant yields, therefore stratifying the patient population based on early observation. Abstract : The vision for autologous cell therapy manufacturing is to deliver consistent products. However, for autologous cell therapies, variability in patient cell quality can result in significant challenges for manufacturing, particularly where there is substantial variability due to patient age and disease status. In this study, the authors show that donor variability in cell expansion potential exists even when using cells from a range of young healthy donors, therefore reinforcing the need to control manufacturing and identify failure earlier in the process.