Stem cells have the potential to yield a consistent source of many differentiated cell types that cannot be grown in culture today. This unique property will be leveraged for therapeutic purposes with more immediate applications in drug discovery and development processes such as screening and investigative toxicity.
Large-scale “industrialized” production of human stem cells in tightly controlled conditions will be required to deliver the quantity and quality of cells needed to support these activities. What is needed to achieve this level of production while meeting rigorous quality and regulatory standards? The solution consists of re-engineering existing process-scale technologies and creating new scalable, optimized approaches.
cGMP Culture Conditions
As more stem cell-based therapeutics progress toward clinical testing, the consistency, quality, and reproducibility of large-scale in vitro systems become an imperative. Development of cGMP conditions for growing and harvesting cells will be necessary to ensure cell populations with uniform phenotypes and predictable behaviors.
Current protocols used to direct stem cell differentiation typically do not yield homogenous cell populations. Attempts to drive such cultures toward a more homogenous and specific population can result in the loss of a significant percentage of cells. Characterization of cells within a heterogeneous population thus becomes critically important, especially when culturing cells for therapeutic purposes.
A number of techniques can be used to enrich a desired cell population including magnetic particles, affinity-based methods, and selected killing of unwanted cells. Enriching large-scale cultures, however, can be technically challenging. Existing processes are not always scalable and are unlikely to yield cultures with only the desired cell type. Furthermore, the quality control steps used during enrichment require the sacrifice of many cells, thus depleting the population.
Integrated "Manufacturing" Systems
Challenges exist throughout the entire scale-up process when culturing large stem cells for therapeutic use. Because the cells themselves are the “product,” the culture system itself must:
• help minimize variability in the cell population;
• effectively control differentiation;
• enable harvesting and formulation without damaging cells; and
• incorporate processes to ensure viability during storage, transport, and administration.
Achieving large-scale production of stem cells while meeting rigorous quality and regulatory standards will depend on further progress in the areas of cell culture and scale-up, characterization, enrichment, purification, and process control to deliver a consistent and reproducible supply of cells in a safe and cost-effective manner.