دورية أكاديمية
أعرض في EDS

Hypoimmunogenic human iPSCs expressing HLA-G, PD-L1, and PD-L2 evade innate and adaptive immunity.

التفاصيل البيبلوغرافية
العنوان: Hypoimmunogenic human iPSCs expressing HLA-G, PD-L1, and PD-L2 evade innate and adaptive immunity.
المؤلفون: Tsuneyoshi N; HEALIOS K.K. Kobe Research Institute, Kobe KIMEC Center Bldg. 3F, 1-5-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo, 650-0047, Japan., Hosoya T; HEALIOS K.K. Kobe Research Institute, Kobe KIMEC Center Bldg. 3F, 1-5-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo, 650-0047, Japan., Takeno Y; HEALIOS K.K. Kobe Research Institute, Kobe KIMEC Center Bldg. 3F, 1-5-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo, 650-0047, Japan., Saitoh K; HEALIOS K.K. Kobe Research Institute, Kobe KIMEC Center Bldg. 3F, 1-5-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo, 650-0047, Japan., Murai H; HEALIOS K.K. Kobe Research Institute, Kobe KIMEC Center Bldg. 3F, 1-5-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo, 650-0047, Japan., Amimoto N; HEALIOS K.K. Kobe Research Institute, Kobe KIMEC Center Bldg. 3F, 1-5-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo, 650-0047, Japan., Tatsumi R; HEALIOS K.K. Kobe Research Institute, Kobe KIMEC Center Bldg. 3F, 1-5-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo, 650-0047, Japan., Watanabe S; HEALIOS K.K. Kobe Research Institute, Kobe KIMEC Center Bldg. 3F, 1-5-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo, 650-0047, Japan., Hasegawa Y; HEALIOS K.K. Kobe Research Institute, Kobe KIMEC Center Bldg. 3F, 1-5-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo, 650-0047, Japan., Kikkawa E; HEALIOS K.K. Kobe Research Institute, Kobe KIMEC Center Bldg. 3F, 1-5-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo, 650-0047, Japan., Goto K; HEALIOS K.K. Kobe Research Institute, Kobe KIMEC Center Bldg. 3F, 1-5-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo, 650-0047, Japan., Nishigaki F; HEALIOS K.K. Kobe Research Institute, Kobe KIMEC Center Bldg. 3F, 1-5-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo, 650-0047, Japan., Tamura K; HEALIOS K.K. Kobe Research Institute, Kobe KIMEC Center Bldg. 3F, 1-5-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo, 650-0047, Japan. k.tamura@healios.jp., Kimura H; HEALIOS K.K. Kobe Research Institute, Kobe KIMEC Center Bldg. 3F, 1-5-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo, 650-0047, Japan. h.kimura@healios.jp.
المصدر: Stem cell research & therapy [Stem Cell Res Ther] 2024 Jul 02; Vol. 15 (1), pp. 193. Date of Electronic Publication: 2024 Jul 02.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101527581 Publication Model: Electronic Cited Medium: Internet ISSN: 1757-6512 (Electronic) Linking ISSN: 17576512 NLM ISO Abbreviation: Stem Cell Res Ther Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central
مواضيع طبية MeSH: Induced Pluripotent Stem Cells*/metabolism , Induced Pluripotent Stem Cells*/cytology , Induced Pluripotent Stem Cells*/immunology , B7-H1 Antigen*/metabolism , B7-H1 Antigen*/genetics , B7-H1 Antigen*/immunology , Adaptive Immunity* , Immunity, Innate* , HLA-G Antigens*/genetics , HLA-G Antigens*/metabolism , HLA-G Antigens*/immunology , Programmed Cell Death 1 Ligand 2 Protein*/metabolism , Programmed Cell Death 1 Ligand 2 Protein*/genetics, Humans ; Animals ; Mice
مستخلص: Background: The human induced pluripotent stem cells (hiPSCs) can generate all the cells composing the human body, theoretically. Therefore, hiPSCs are thought to be a candidate source of stem cells for regenerative medicine. The major challenge of allogeneic hiPSC-derived cell products is their immunogenicity. The hypoimmunogenic cell strategy is allogenic cell therapy without using immune suppressants. Advances in gene engineering technology now permit the generation of hypoimmunogenic cells to avoid allogeneic immune rejection. In this study, we generated a hypoimmunogenic hiPSC (HyPSC) clone that had diminished expression of human leukocyte antigen (HLA) class Ia and class II and expressed immune checkpoint molecules and a safety switch.
Methods: First, we generated HLA class Ia and class II double knockout (HLA class Ia/II DKO) hiPSCs. Then, a HyPSC clone was generated by introducing exogenous β-2-microglobulin (B2M), HLA-G, PD-L1, and PD-L2 genes, and the Rapamycin-activated Caspase 9 (RapaCasp9)-based suicide gene as a safety switch into the HLA class Ia/II DKO hiPSCs. The characteristics and immunogenicity of the HyPSCs and their derivatives were analyzed.
Results: We found that the expression of HLA-G on the cell surface can be enhanced by introducing the exogenous HLA-G gene along with B2M gene into HLA class Ia/II DKO hiPSCs. The HyPSCs retained a normal karyotype and had the characteristics of pluripotent stem cells. Moreover, the HyPSCs could differentiate into cells of all three germ layer lineages including CD45 + hematopoietic progenitor cells (HPCs), functional endothelial cells, and hepatocytes. The HyPSCs-derived HPCs exhibited the ability to evade innate and adaptive immunity. Further, we demonstrated that RapaCasp9 could be used as a safety switch in vitro and in vivo.
Conclusion: The HLA class Ia/II DKO hiPSCs armed with HLA-G, PD-L1, PD-L2, and RapaCasp9 molecules are a potential source of stem cells for allogeneic transplantation.
(© 2024. The Author(s).)
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فهرسة مساهمة: Keywords: Gene engineering; HLA-G; Human iPSC; Hypoimmunogenic pluripotent cells; PD-L1; PD-L2; Suicide gene
المشرفين على المادة: 0 (B7-H1 Antigen)
0 (HLA-G Antigens)
0 (Programmed Cell Death 1 Ligand 2 Protein)
0 (CD274 protein, human)
0 (PDCD1LG2 protein, human)
تواريخ الأحداث: Date Created: 20240703 Date Completed: 20240703 Latest Revision: 20240725
رمز التحديث: 20240726
مُعرف محوري في PubMed: PMC11218117
DOI: 10.1186/s13287-024-03810-4
PMID: 38956724
قاعدة البيانات: MEDLINE
الوصف
تدمد:1757-6512
DOI:10.1186/s13287-024-03810-4