Development of immunocompatible pluripotent stem cells via CRISPR-based human leukocyte antigen engineering

• Published in: Experimental & molecular medicine Vol. 51; no. 1; pp. 1 - 11
• Main Authors: Jang, Yeonsue, Choi, Jinhyeok, Park, Narae, Kang, Jaewoo, Kim, Myungshin, Kim, Yonggoo, Ju, Ji Hyeon
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 07.01.2019; Nature Publishing Group UK; Nature Publishing Group; 생화학분자생물학회
• Subjects: Animals; Antigens; Antisera; Cell lines; Cells, Cultured; CRISPR; CRISPR-Cas Systems; Graft rejection; Histocompatibility; Histocompatibility antigen HLA; HLA Antigens - genetics; Humans; Immunogenicity; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - immunology; Induced Pluripotent Stem Cells - transplantation; Male; Mice; Mice, Nude; Pluripotency; Stem cell transplantation; Stem cells; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/s12276-018-0190-2

Pluripotent stem cell transplantation is a promising regenerative strategy for treating intractable diseases. However, securing human leukocyte antigen (HLA)-matched donor stem cells is extremely difficult. The traditional approach for generating such cells is to establish homozygous pluripotent stem cell lines. Unfortunately, because of HLA diversity, this strategy is too time-consuming to be of practical use. HLA engineering of donor stem cells has been proposed recently as a means to evade graft-versus-host rejection in stem cell allotransplantation. This approach would be advantageous in both time and cost to the traditional method, but its feasibility must be investigated. In this study, we used CRISPR/Cas9 to knockout HLA-B from inducible pluripotent stem cells (iPSCs) with heterogenous HLA-B and showed that the HLA-B knockout iPSCs resulted in less immunogenicity in HLA-B antisera than that in the control. Our results support the feasibility of HLA-engineered iPSCs in stem cell allotransplantation.