In Vivo Tumorigenicity of the 20q11.21 Amplicon in an Engraftment Model of hPSCs and Differentiated Liver Cells

• DOI: 10.46582/jsrm.1901002
• Publication Date: 2023-06-17T01:15:32Z
• Authors: Chris S. Pridgeon; Shiva S. Forootan; Fang Zhang; Nicholas W. Harper; Daniel H. Palmer; Richard Weightmann; Siân Gregory; Zoë Hewitt; Duncan Baker; Jason A. Halliwell; H. D. M. Moore; Emanuele Ricci; Peter W. Andrews; Harish Poptani; David C. Hay; B. Kevin Park; Christopher E. Go...
• Keywords: Amplicon

Human pluripotent stem cells (hPSCs) are a promising source of somatic for clinical applications and disease modelling. However, during culture they accumulate genetic aberrations such as amplification 20q11.21 which occurs in approximately 20% extensively cultured hPSC lines confers BCL2L1-mediated survival advantage. During the production large number required transplantation therapy these may become unavoidable has important safety implications therapies also impact upon Presently, risks poorly understood; whilst it is apparent that large-scale can pose an oncogenic risk, associated with smaller, more insidious changes have not been fully explored. In this report, effects engraftment human embryonic (hESCs) hESC-derived hepatocyte-like (HLCs) without minimal amplicon isochromosome 20q (i20q) SCID-beige mice presented. The were tracked vivo using luminescent reporter over period four months. Intrasplenic injection hESCs showed greater potential formation severely disruptive lesions liver spleen animals injected containing compared i20q wild type. HLCs engrafted successfully formed than type or i20q. These results reinforce notion karyotyping therapeutic transplant, suggest screening known common necessary. Further work to identify commonly arising should be performed routine hPSCs intended use used.