The Role of Preservation in the Variability of Regenerative Medicine Products

Abstract: Regenerative medicine (RM) has the potential to restore or establish normal function of cells, tissues, and organs that have been lost due to age, disease, or injury. It is common for the site of raw material collection, site of manufacture, and site of clinical use to be different for RM products, and at the same time, cells must remain viable and functional during transportation among different sites. Freezing products down to cryogenic temperatures along with cold chain transportation has become an effective method of preserving RM products. The quality of RM products along this supply chain represents the cumulative effects of all of the processing steps and all of the reagents used in the process. A variety of sources of variability in the preservation of RM products can result in both cell losses and greater variability in the quality of RM products. The purpose of this article is to review the sources of variability in the preservation process as well as the methods by which variability can be controlled or avoided. Lay Summary: RM products involving the use of allogeneic or autologous cells and tissues are typically cryopreserved before shipping. Each step of the preservation process is a potential source of variability and can probably result in variability in the quality of RM products. This review provides an overview of the sources of variability in the processing of preservation and simple practices that can be used to control or reduce the variability. Future work will focus on incorporation of clinical outcomes with processing that has been performed to identify the root cause of quality inconsistency of RM products, as well as exploring the possibilities of simplifying and automating processing steps of preservation in order to reduce the overall variability that might be present.