First, Do no Harm: Current Approaches to Assess Tumorigenicity in Stem Cell-derived Therapeutic Products

Abstract

Stem cells hold a great promise for regenerative medicine given their ability to proliferate and differentiate into various cell types. However, self-renewal and multipotency also grant a high capacity to form tumor tissues in vivo post-therapeutic administration. Indeed, multiple case reports have revealed the formation of stem cell derived tumors, such as teratoma, in animal models and even in clinical applications. As a result, examination of tumorigenicity becomes one of the major considerations when assessing the safety of stem cell-derived therapeutic products. Ideally, the assessment needs to be performed in a rapid, sensitive, cost-effective, and scalable manner. In this chapter, the current practices of assay development to fulfill this demand are reviewed. Progress in animal models, soft agar culture, PCR, flow cytometry, and microfluidics are introduced and compared comprehensively. Some insights regarding the assay selection and future development are also provided as there is no one-for-all assay at this moment.

Keywords: Assay development, Biomanufacturing, Cell therapy, Cancer initiation, Quality assurance, Stem cells, Tumorigenicity.

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