{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sartori-Maldonado R"],"funding":["Finnish Cultural Foundation","Magnus Ehrnrooth Fundation","Bo and Kerstin Hjelt Diabetes Foundation","The Paulo Foundation","HUS Group","Finnish Red Cross Blood Service","Childhood Disease Research Fundation","Signe and Ane Gyllenberg Foundation","Diabetes Research Foundation","K Albin Johansson Foundation","Ida Mont Fundation","Novo Nordisk Fonden"],"pagination":["2535-2548"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11405178"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["32(8)"],"pubmed_abstract":["Stem and progenitor cells hold great promise for regenerative medicine and gene therapy approaches. However, transplantation of living cells entails a fundamental risk of unwanted growth, potentially exacerbated by CRISPR-Cas9 or other genetic manipulations. Here, we describe a safety system to control cell proliferation while allowing robust and efficient cell manufacture, without any added genetic elements. Inactivating TYMS, a key nucleotide metabolism enzyme, in several cell lines resulted in cells that proliferate only when supplemented with exogenous thymidine. Under supplementation, TYMS<sup>-/-</sup>-pluripotent stem cells proliferate, produce teratomas, and successfully differentiate into potentially therapeutic cell types such as pancreatic β cells. Our results suggest that suppl"],"journal":["Molecular therapy : the journal of the American Society of Gene Therapy"],"pubmed_title":["Thymidylate synthase disruption to limit cell proliferation in cell therapies."],"pmcid":["PMC11405178"],"funding_grant_id":["NNF22OC0078484","NNF19OC0057286"],"pubmed_authors":["Balaz M","Soppa I","Eurola S","Wartiovaara K","Juutila J","Puttonen H","Saarimaki-Vire J","Sartori-Maldonado R","Montaser H","Otonkoski T"],"additional_accession":[]},"is_claimable":false,"name":"Thymidylate synthase disruption to limit cell proliferation in cell therapies.","description":"Stem and progenitor cells hold great promise for regenerative medicine and gene therapy approaches. However, transplantation of living cells entails a fundamental risk of unwanted growth, potentially exacerbated by CRISPR-Cas9 or other genetic manipulations. Here, we describe a safety system to control cell proliferation while allowing robust and efficient cell manufacture, without any added genetic elements. Inactivating TYMS, a key nucleotide metabolism enzyme, in several cell lines resulted in cells that proliferate only when supplemented with exogenous thymidine. Under supplementation, TYMS<sup>-/-</sup>-pluripotent stem cells proliferate, produce teratomas, and successfully differentiate into potentially therapeutic cell types such as pancreatic β cells. Our results suggest that suppl","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Aug","modification":"2026-06-02T22:17:55.66Z","creation":"2025-04-06T12:30:50.904Z"},"accession":"S-EPMC11405178","cross_references":{"pubmed":["38867450"],"doi":["10.1016/j.ymthe.2024.06.014"]}}