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

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Pluripotent Stem Cell Therapy for Diabetes

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Abstract

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.

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  1. Sanne Hillenius and Joaquin Montilla-Rojo contributed equally.

Authors and Affiliations

  1. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

    Sanne Hillenius, Thomas F. Eleveld & Leendert H. J. Looijenga

  2. Anatomy and Physiology, Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL, Utrecht, The Netherlands

    Joaquin Montilla-Rojo & Daniela C. F. Salvatori

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  1. Diabetes Research Institute and Clinical Unit of Regenerative Medicine and Transplant, IRCCS San Raffaele Hospital/Vita-Salute San Raffaele University, Milan, Italy

    Lorenzo Piemonti

  2. Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

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  3. University of British Columbia, Vancouver, BC, Canada

    Timothy J . Kieffer

  4. IRCCS Ospedale San Raffaele, Diabetes Research Institute, Milan, Italy

    Valeria Sordi

  5. Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

    Eelco de Koning

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Hillenius, S., Montilla-Rojo, J., Eleveld, T.F., Salvatori, D.C.F., Looijenga, L.H.J. (2023). Safety Issues Related to Pluripotent Stem Cell-Based Therapies: Tumour Risk. In: Piemonti, L., Odorico, J., Kieffer, T.J..., Sordi, V., de Koning, E. (eds) Pluripotent Stem Cell Therapy for Diabetes. Springer, Cham. https://doi.org/10.1007/978-3-031-41943-0_18

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