Strategies for Genetically Engineering Hypoimmunogenic Universal Pluripotent Stem Cells

Wei Zhao, Anhua Lei, Lin Tian, Xudong Wang, Cristina Correia, Taylor Weiskittel, Hu Li, Alan Trounson, Qiuli Fu, Ke Yao, Jin Zhang

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number101162
JournaliScience
Volume23
Issue number6
DOIs
StatePublished - Jun 26 2020

Keywords

  • Biological Sciences
  • Cell Biology
  • Genetic Engineering
  • Stem Cells Research

ASJC Scopus subject areas

  • General

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