Cost-Effective Master Cell Bank Validation of Multiple Clinical-Grade Human Pluripotent Stem Cell Lines From a Single Donor. (13th August 2014)

• Record Type: Journal Article
• Authors: Devito, Liani; Petrova, Anastasia; Miere, Cristian; Codognotto, Stefano; Blakely, Nicola; Lovatt, Archie; Ogilvie, Caroline; Khalaf, Yacoub; Ilic, Dusko
• Is Part Of: Stem cells translational medicine. Volume 3:Number 10(2014)
• Page Start: 1116
• Page End: 1124
• Publication Date: 2014-08-13
• Subjects: Clinical-grade human embryonic stem cell lines -- Clinical-grade iPS cell lines -- Current good manufacturing practice -- Validation -- Master cell bank -- Human viral pathogens; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.5966/sctm.2014-0015
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract: Standardization guidelines for human pluripotent stem cells are still very broadly defined, despite ongoing clinical trials in the U.S., U.K., and Japan. The requirements for validation of human embryonic (hESCs) and induced pluripotent stem cells (iPSCs) in general follow the regulations for other clinically compliant biologics already in place but without addressing key differences between cell types or final products. In order to realize the full potential of stem cell therapy, validation criteria, methodology, and, most importantly, strategy, should address the shortfalls and efficiency of current approaches; without this, hESC- and, especially, iPSC-based therapy will not be able to compete with other technologies in a cost-efficient way. We addressed the protocols for testing cell lines for human viral pathogens and propose a novel strategy that would significantly reduce costs. It is highly unlikely that the multiple cell lines derived in parallel from a tissue sample taken from one donor would have different profiles of endogenous viral pathogens; we therefore argue that samples from the Master Cell Banks of sibling lines could be safely pooled for validation. We illustrate this approach with tiered validation of two sibling clinical-grade hESC lines, KCL033 and KCL034 (stage 1, sterility; stage 2, specific human pathogens; and stage 3, nonspecific human pathogens). The results of all tests were negative. This cost-effective strategy could also be applied for validation of Master Cell Banks of multiple clinical-grade iPSC lines derived from a single donor. Abstract : This study addressed protocols for testing cell lines for human viral pathogens. It is highly unlikely that multiple cell lines derived in parallel from tissue samples taken from one donor would have different endogenous viral pathogen profiles. Master Cell Banks of sibling lines were pooled for tiered validation; all results were negative. This cost-effective strategy could be applied for validation of Master Cell Banks of multiple clinical-grade iPS cell lines from a single donor.