DOI QR코드

DOI QR Code

Expression of Major Histocompatibility Complex during Neuronal Differentiation of Somatic Cell Nuclear Transfer-Human Embryonic Stem Cells

  • Jin Saem Lee (Graduate School of Biomedical Science and Engineering, Hanyang University) ;
  • Jeoung Eun Lee (CHA Advanced Research Institute, CHA University) ;
  • Shin-Hye Yu (Graduate School of Biomedical Science and Engineering, Hanyang University) ;
  • Taehoon Chun (Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University) ;
  • Mi-Yoon Chang (Department of Premedicine, College of Medicine, Hanyang University) ;
  • Dong Ryul Lee (CHA Advanced Research Institute, CHA University) ;
  • Chang-Hwan Park (Graduate School of Biomedical Science and Engineering, Hanyang University)
  • Received : 2023.03.27
  • Accepted : 2023.09.08
  • Published : 2024.02.28

Abstract

Human pluripotent stem cells (hPSCs) such as human embryonic stem cells (hESCs), induced pluripotent stem cells, and somatic cell nuclear transfer (SCNT)-hESCs can permanently self-renew while maintaining their capacity to differentiate into any type of somatic cells, thereby serving as an important cell source for cell therapy. However, there are persistent challenges in the application of hPSCs in clinical trials, where one of the most significant is graft rejection by the patient immune system in response to human leukocyte antigen (HLA) mismatch when transplants are obtained from an allogeneic (non-self) cell source. Homozygous SCNT-hESCs (homo-SCNT-hESCs) were used to simplify the clinical application and to reduce HLA mismatch. Here, we present a xeno-free protocol that confirms the efficient generation of neural precursor cells in hPSCs and also the differentiation of dopaminergic neurons. Additionally, there was no difference when comparing the HLA expression patterns of hESC, homo-SCNT-hESCs and hetero-SCNT-hESCs. We propose that there are no differences in the differentiation capacity and HLA expression among hPSCs that can be cultured in vitro. Thus, it is expected that homo-SCNT-hESCs will possess a wider range of applications when transplanted with neural precursor cells in the context of clinical trials.

Keywords

Acknowledgement

This research was supported by grants from the Basic Science Research Program (NRF-2019R1A2C2005681) and the Bio & Medical Technology Development Program (NRF-2022M3A9I2082319) funded by the Ministry of Science and ICT, Republic of Korea.

References

  1. Cho MS, Hwang DY, Kim DW. Efficient derivation of functional dopaminergic neurons from human embryonic stem cells on a large scale. Nat Protoc 2008;3:1888-1894
  2. Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998;282:1145-1147 Erratum in: Science 1998;282:1827
  3. Chung YG, Eum JH, Lee JE, et al. Human somatic cell nuclear transfer using adult cells. Cell Stem Cell 2014;14:777-780
  4. Matoba S, Liu Y, Lu F, et al. Embryonic development following somatic cell nuclear transfer impeded by persisting histone methylation. Cell 2014;159:884-895
  5. Chung YG, Matoba S, Liu Y, et al. Histone demethylase expression enhances human somatic cell nuclear transfer efficiency and promotes derivation of pluripotent stem cells. Cell Stem Cell 2015;17:758-766
  6. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861-872
  7. Schwartz SD, Hubschman JP, Heilwell G, et al. Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet 2012;379:713-720.
  8. Kim JH, Auerbach JM, Rodriguez-Gomez JA, et al. Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Nature 2002;418:50-56
  9. Laflamme MA, Chen KY, Naumova AV, et al. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 2007;25:1015-1024
  10. van Berlo JH, Molkentin JD. An emerging consensus on cardiac regeneration. Nat Med 2014;20:1386-1393
  11. Williams RC, Opelz G, Weil EJ, McGarvey CJ, Chakkera HA. The risk of transplant failure with HLA mismatch in first adult kidney allografts 2: living donors, summary, guide. Transplant Direct 2017;3:e152
  12. Gottwald W. [Neurologic and psychiatric syndromes in lupus erythematosus]. Z Hautkr 1978;53:505-514 German.
  13. Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 1998;392:86-89
  14. Doyle C, Strominger JL. Interaction between CD4 and class II MHC molecules mediates cell adhesion. 1987. J Immunol 2010;184:5935-5938
  15. Ichise H, Nagano S, Maeda T, et al. NK cell alloreactivity against KIR-ligand-mismatched HLA-haploidentical tissue derived from HLA haplotype-homozygous iPSCs. Stem Cell Reports 2017;9:853-867
  16. Kruse V, Hamann C, Monecke S, et al. Human induced pluripotent stem cells are targets for allogeneic and autologous natural killer (NK) cells and killing is partly mediated by the activating NK receptor DNAM-1. PLoS One 2015;10:e0125544
  17. McGranahan N, Rosenthal R, Hiley CT, et al. Allele-specific HLA loss and immune escape in lung cancer evolution. Cell 2017;171:1259-1271.e11
  18. Lee KW, Oh DH, Lee C, Yang SY. Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population. Tissue Antigens 2005;65:437-447
  19. Yang G, Deng YJ, Hu SN, et al. HLA-A, -B, and -DRB1 polymorphism defined by sequence-based typing of the Han population in Northern China. Tissue Antigens 2006;67:146-152
  20. Lee EH, Park CH. Comparison of reprogramming methods for generation of induced-oligodendrocyte precursor cells. Biomol Ther (Seoul) 2017;25:362-366
  21. Mandai M, Watanabe A, Kurimoto Y, et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N Engl J Med 2017;376:1038-1046
  22. Lipsitz YY, Timmins NE, Zandstra PW. Quality cell therapy manufacturing by design. Nat Biotechnol 2016;34:393-400
  23. Chakradhar S. An eye to the future: researchers debate best path for stem cell-derived therapies. Nat Med 2016;22:116-119
  24. Krystkowiak P, Gaura V, Labalette M, et al. Alloimmunisation to donor antigens and immune rejection following foetal neural grafts to the brain in patients with Huntington's disease. PLoS One 2007;2:e166
  25. Brundin P, Pogarell O, Hagell P, et al. Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson's disease. Brain 2000;123(Pt 7):1380-1390
  26. Barker RA, Drouin-Ouellet J, Parmar M. Cell-based therapies for Parkinson disease-past insights and future potential. Nat Rev Neurol 2015;11:492-503
  27. Sette A, Sidney J. HLA supertypes and supermotifs: a functional perspective on HLA polymorphism. Curr Opin Immunol 1998;10:478-482
  28. Williams TM. Human leukocyte antigen gene polymorphism and the histocompatibility laboratory. J Mol Diagn 2001;3:98-104
  29. Gallardo D, Brunet S, Torres A, et al. Hla-DPB1 mismatch in HLA-A-B-DRB1 identical sibling donor stem cell transplantation and acute graft-versus-host disease. Transplantation 2004;77:1107-1110
  30. Park MH, Kim HS, Kang SJ. HLA-A,-B,-DRB1 allele and haplotype frequencies in 510 Koreans. Tissue Antigens 1999;53(4 Pt 1):386-390
  31. Deuse T, Hu X, Gravina A, et al. Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat Biotechnol 2019;37:252-258 Erratum in: Nat Biotechnol 2022;40:1690
  32. Xu H, Wang B, Ono M, et al. Targeted disruption of HLA genes via CRISPR-Cas9 generates iPSCs with enhanced immune compatibility. Cell Stem Cell 2019;24:566-578.e7
  33. Morizane A, Kikuchi T, Hayashi T, et al. MHC matching improves engraftment of iPSC-derived neurons in non-human primates. Nat Commun 2017;8:385
  34. Araki R, Uda M, Hoki Y, et al. Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. Nature 2013;494:100-104
  35. Morizane A, Doi D, Kikuchi T, et al. Direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a non-human primate. Stem Cell Reports 2013;1:283-292
  36. Zhao T, Zhang ZN, Rong Z, Xu Y. Immunogenicity of induced pluripotent stem cells. Nature 2011;474:212-215
  37. de Almeida PE, Meyer EH, Kooreman NG, et al. Transplanted terminally differentiated induced pluripotent stem cells are accepted by immune mechanisms similar to self-tolerance. Nat Commun 2014;5:3903
  38. Zhao T, Zhang ZN, Westenskow PD, et al. Humanized mice reveal differential immunogenicity of cells derived from autologous induced pluripotent stem cells. Cell Stem Cell 2015;17:353-359