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Treating iPSC-Derived β Cells with an Anti-CD30 Antibody–Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation
Insulin-producing cells derived from induced pluripotent stem cells (iPSCs) are promising candidates for β cell replacement in type 1 diabetes. However, the risk of teratoma formation due to residual undifferentiated iPSCs contaminating the differentiated cells is still a critical concern for clinic...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456216/ https://www.ncbi.nlm.nih.gov/pubmed/36077097 http://dx.doi.org/10.3390/ijms23179699 |
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author | Pellegrini, Silvia Zamarian, Valentina Landi, Elisa Cospito, Alessandro Lombardo, Marta Tiffany Manenti, Fabio Citro, Antonio Schiavo Lena, Marco Piemonti, Lorenzo Sordi, Valeria |
author_facet | Pellegrini, Silvia Zamarian, Valentina Landi, Elisa Cospito, Alessandro Lombardo, Marta Tiffany Manenti, Fabio Citro, Antonio Schiavo Lena, Marco Piemonti, Lorenzo Sordi, Valeria |
author_sort | Pellegrini, Silvia |
collection | PubMed |
description | Insulin-producing cells derived from induced pluripotent stem cells (iPSCs) are promising candidates for β cell replacement in type 1 diabetes. However, the risk of teratoma formation due to residual undifferentiated iPSCs contaminating the differentiated cells is still a critical concern for clinical application. Here, we hypothesized that pretreatment of iPSC-derived insulin-producing cells with an anti-CD30 antibody–drug conjugate could prevent in vivo teratoma formation by selectively killing residual undifferentiated cells. CD30 is expressed in all human iPSCs clones tested by flow cytometry (n = 7) but not in iPSC-derived β cells (iβs). Concordantly, anti-CD30 treatment in vitro for 24 h induced a dose-dependent cell death (up to 90%) in human iPSCs while it did not kill iβs nor had an impact on iβ identity and function, including capacity to secrete insulin in response to stimuli. In a model of teratoma assay associated with iβ transplantation, the pretreatment of cells with anti-CD30 for 24 h before the implantation into NOD-SCID mice completely eliminated teratoma development (0/10 vs. 8/8, p < 0.01). These findings suggest that short-term in vitro treatment with clinical-grade anti-CD30, targeting residual undifferentiated cells, eliminates the tumorigenicity of iPSC-derived β cells, potentially providing enhanced safety for iPSC-based β cell replacement therapy in clinical scenarios. |
format | Online Article Text |
id | pubmed-9456216 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94562162022-09-09 Treating iPSC-Derived β Cells with an Anti-CD30 Antibody–Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation Pellegrini, Silvia Zamarian, Valentina Landi, Elisa Cospito, Alessandro Lombardo, Marta Tiffany Manenti, Fabio Citro, Antonio Schiavo Lena, Marco Piemonti, Lorenzo Sordi, Valeria Int J Mol Sci Article Insulin-producing cells derived from induced pluripotent stem cells (iPSCs) are promising candidates for β cell replacement in type 1 diabetes. However, the risk of teratoma formation due to residual undifferentiated iPSCs contaminating the differentiated cells is still a critical concern for clinical application. Here, we hypothesized that pretreatment of iPSC-derived insulin-producing cells with an anti-CD30 antibody–drug conjugate could prevent in vivo teratoma formation by selectively killing residual undifferentiated cells. CD30 is expressed in all human iPSCs clones tested by flow cytometry (n = 7) but not in iPSC-derived β cells (iβs). Concordantly, anti-CD30 treatment in vitro for 24 h induced a dose-dependent cell death (up to 90%) in human iPSCs while it did not kill iβs nor had an impact on iβ identity and function, including capacity to secrete insulin in response to stimuli. In a model of teratoma assay associated with iβ transplantation, the pretreatment of cells with anti-CD30 for 24 h before the implantation into NOD-SCID mice completely eliminated teratoma development (0/10 vs. 8/8, p < 0.01). These findings suggest that short-term in vitro treatment with clinical-grade anti-CD30, targeting residual undifferentiated cells, eliminates the tumorigenicity of iPSC-derived β cells, potentially providing enhanced safety for iPSC-based β cell replacement therapy in clinical scenarios. MDPI 2022-08-26 /pmc/articles/PMC9456216/ /pubmed/36077097 http://dx.doi.org/10.3390/ijms23179699 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Pellegrini, Silvia Zamarian, Valentina Landi, Elisa Cospito, Alessandro Lombardo, Marta Tiffany Manenti, Fabio Citro, Antonio Schiavo Lena, Marco Piemonti, Lorenzo Sordi, Valeria Treating iPSC-Derived β Cells with an Anti-CD30 Antibody–Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation |
title | Treating iPSC-Derived β Cells with an Anti-CD30 Antibody–Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation |
title_full | Treating iPSC-Derived β Cells with an Anti-CD30 Antibody–Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation |
title_fullStr | Treating iPSC-Derived β Cells with an Anti-CD30 Antibody–Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation |
title_full_unstemmed | Treating iPSC-Derived β Cells with an Anti-CD30 Antibody–Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation |
title_short | Treating iPSC-Derived β Cells with an Anti-CD30 Antibody–Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation |
title_sort | treating ipsc-derived β cells with an anti-cd30 antibody–drug conjugate eliminates the risk of teratoma development upon transplantation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456216/ https://www.ncbi.nlm.nih.gov/pubmed/36077097 http://dx.doi.org/10.3390/ijms23179699 |
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