Capsule

What’s new, what’s hot, what’s timely? If you don’t have time to search the Internet for the latest developments that might affect your work environment, you just might find some of that information in this Capsule column. Please e-mail any comments, suggestions, or insights to Robert A. Rasmussen at [e-mail].

A Compelling Reason to Maintain the OSHA Blood-Borne Pathogen Standard for Human Stem Cell Work Beyond the Potential Risk of Pathogen Exposure

Human stem cells, both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are being used in many experimental settings, ranging from the elucidation of cell and tissue differentiation mechanisms to their clinical use in cell replacement or gene therapy for certain diseases. The Occupational Safety and Health Administration (OSHA) Blood-Borne Pathogen Standard was enacted to prevent the accidental infection of laboratory and clinical workers with human pathogens (HepB, HepC, HIV, et al) that may be present in human biological samples. As with any human materials used in a research laboratory, human ESCs or iPSCs should be handled according to the OSHA standard. Yet, all stem cells earmarked for clinical use have tested negative for human pathogens, as have most human pluripotent stem cell lines available for laboratory use. Armed with this knowledge, ESC and iPSC researchers may be tempted to relax their biosafety risk concerns. However, the biohazard risks from an accidental exposure to human stem cells may be higher than many realize.

Accidental parenteral exposure to any human cells, including human tumor cells or cell lines (from a nonautologous donor not genetically identical to the exposed person) normally initiates an allogeneic immune response in the exposed person that rejects and kills those cells (there have been rare, isolated instances of tumor formation resulting from such exposures). However, there is evidence that ESCs may be less prone to rejection by these same immune mechanisms. ¹ Moreover, a recent study by Merkle et al ² demonstrated that a number of human stem cell lines have an inactivating mutation in the gene that codes for the tumor suppressor p53. This is important because inactivating mutations in the TP53 gene coding for p53 are associated with a large number of human cancers. Whole exon sequencing analysis of 140 independent human embryonic stem cell lines from the National Institutes of Health, plus 26 additional cell lines prepared for clinical use under good manufacturing practice conditions, revealed 6 dominant negative TP53 mutations in 5 unrelated cell lines. Comparing the TP53 mutational incidence with the passage number of cultured pluripotent stem cells strongly suggested that stem cells with TP53 mutations have a selective growth advantage over cells with a normally functioning TP53 gene. Furthermore, an analysis by the same group of published DNA sequences of an additional 117 human stem cell lines found another 9 TP53 mutations. The results suggest that TP53 mutations may arise and be present in any ESC or iPSC line, even if such mutants may not be present in earlier cell passages.

While these results clearly have serious implications for using ESCs or iPSCs in clinical trials, they indicate an additional biosafety risk associated with their use in the laboratory.