Cryopreservation and Cell Banking for Autologous Mesenchymal Stem Cell-Based Therapies

Abstract

As cell-based therapies begin to progress through Phase III clinical trials, there is an increasing need for the development of comprehensive cell banking strategies. In order to achieve commercial viability, both autologous and allogeneic approaches must have a comprehensive, end-to-end cell banking model-including proper collection, manufacturing and release criteria, cryopreservation and storage of cells, shipping, delivery, and logistics management of the final cell product. By developing an understanding of industry standards and best practices across these areas, companies can be better positioned to reduce research costs, improve efficiencies, create revenue streams, decrease time to discovery and, ideally, increase the likelihood and number of approved marketed products. The focus of this paper will be on cell banking strategies for autologous-based cell therapies with mesenchymal stromal cells, which are the most widely used cell type in cell therapy clinical trials today.

Adult multipotent stromal cell cryopreservation: Pluses and pitfalls

“…Cell delivery from current Good Manufacturing Processes facilities to patient administration sites requires maintenance of frozen cells for variable time periods despite external temperature fluctuations . Vitrified cells are transported at cryogenic temperatures in dry shippers with liquid nitrogen in absorbent materials to avoid sample contact with liquid .…”

“…Cell aliquots can be maintained for later administration immediately upon revitalization or after short‐term expansion . Cryopreservation also increases MSC availability as frozen cells can be delivered over long distances . Despite prevalent MSC cryopreservation, relatively little focus has been directed toward cell effects.…”

Stem cells; mesenchymal stem cells and current clinical applications

“…Fakat kemik ili¤i kaynaklı olan MHK'ler daha uzun süredir çalııldı¤ı için klinik güvenilirli¤i ve uygulamasına ait veriler de daha fazladır. [15,19,20] Kemik ili¤i kaynaklı mezenkimal kök hücreler (K‹-MKH): Organizmanın en zengin kök hücre kaynaklarından biri sayılan kemik ili¤i stroması hematopoetik ve MKH'leri, endoteliyal hücreleri, fibroblastları, retikulum hücrelerini, adipositleri ve osteogenik hücreleri bir arada içeren heterojenik bir hücre popülasyonudur. Mezenkimal kök hüc-reler kemik ili¤i stromasındaki tüm bu hücrelerin yaklaık %0.01'ini oluturmaktadır.…”

Low temperature cell pausing: an alternative short-term preservation method for use in cell therapies including stem cell applications

“…Furthermore, the use of animal derived components in cryopreservation, such as fetal bovine serum as a vehicle solution, risks contamination with adventitious agents (Merten 1999). Despite some drawbacks, cryopreservation at -80°C or -20°C is commonly used to store and transfer cells between the manufacturing site and medical facility (Coopman 2011;Harel 2013). Research to improve cryopreservation protocols, using safer, naturally derived CPAs such as trehalose, and xeno-free serum alternatives, is in progress for application to therapeutically relevant cells.…”

“…Note: Table 1 to be placed here As MSCs are the most extensively used stem cell in current cell therapy trials (Harel 2013), successful application of cell pausing to MSCs will provide significant benefits. It is clear, however, that knowledge of how to accommodate the metabolic and structural changes of cells during pausing needs to be developed before progressing onto more valuable and expensive cell lines.…”