Safety Issues Related to Pluripotent Stem Cell-Based Therapies: Tumour Risk

As the exciting era of regenerative medicine has dawned, considerable efforts aim to further develop human pluripotent stem cell (hPSC)-based therapies for a plethora of diseases, including diabetes mellitus. However, increasing concerns about their safety have been raised, specifically regarding the risk of tumour formation. Since their initial discovery and derivation several decades ago, it has become evident that hPSCs have a propensity to acquire (epi)genetic aberrations prior to and during culture, with concerning similarities to aberrations observed in many cancers. Moreover, efforts aiming to improve directed differentiation protocols are ongoing; however, the risk of undesired cell populations within the final cell product remains problematic, including residual undifferentiated cell types and off-target derivative cell types. A full understanding of the cause and effect of both acquired (epi)genetic aberrations and undesired cell types is still in its infancy, with little knowledge of their impact and what may define the potential malignant transformation of these cells. Fortunately, unravelling the complexity of these issues is underway in full effect due to a growing arsenal of techniques that enable the assessment of the intrinsic properties and functional effects of both hPSCs and their derivatives. Thus, promising data is continuously being obtained that may ultimately ensure the safe application of hPSC-based therapies. In this chapter, we provide an overview of recurrent (epi)genetic aberrations observed in hPSCs and the similarities to those observed in cancer. Moreover, we provide a catalogue of the techniques that are available to identify and characterise both these aberrations and the undesired cell populations that may be present within the final cell population. A schematic of stem cell therapy with tumor risk. The cultured cells with chromosomes of the original derivative are mutated single nucleotides. It is evaluated for the tumor formation cells and the safety of h P S C-based therapies. The final cell population is the target cells.