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Strategies for Genetically Engineering Hypoimmunogenic Universal Pluripotent Stem Cells

Despite progress in developing cell therapies, such as T cell or stem cell therapies to treat diseases, immunoincompatibility remains a major barrier to clinical application. Given the fact that a host's immune system may reject allogeneic transplanted cells, methods have been developed to gene...

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Detalles Bibliográficos
Autores principales: Zhao, Wei, Lei, Anhua, Tian, Lin, Wang, Xudong, Correia, Cristina, Weiskittel, Taylor, Li, Hu, Trounson, Alan, Fu, Qiuli, Yao, Ke, Zhang, Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270609/
https://www.ncbi.nlm.nih.gov/pubmed/32502965
http://dx.doi.org/10.1016/j.isci.2020.101162
Descripción
Sumario:Despite progress in developing cell therapies, such as T cell or stem cell therapies to treat diseases, immunoincompatibility remains a major barrier to clinical application. Given the fact that a host's immune system may reject allogeneic transplanted cells, methods have been developed to genetically modify patients' primary cells. To advance beyond this time-consuming and costly approach, recent research efforts focus on generating universal pluripotent stem cells to benefit a broader spectrum of patients. In this review, we first summarize current achievements to harness immunosuppressive mechanisms in cells to reduce immunogenicity. Then, we discuss several recent studies demonstrating the feasibility of genetically modifying pluripotent stem cells to escape immune attack and summarize the methods to evaluate hypoimmunogenicity. Although challenges remain, progress to develop genetically engineered universal pluripotent stem cells holds the promise of expediting their use in future gene and cell therapeutics and regenerative medicine.