Lack of T Cell Response to iPSC-Derived Retinal Pigment Epithelial Cells from HLA Homozygous Donors

Sugita, Sunao; Iwasaki, Yuko; Makabe, Kenichi; Kimura, Takafumi; Futagami, Takaomi; Suegami, Shinji; Takahashi, Masayo

doi:10.1016/j.stemcr.2016.08.011

Cited by 94 publications

(100 citation statements)

References 20 publications

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“…The iPS cells are in the preclinical stage, can be generated after inducing the expression of transcription factors associated with pluripotency, and exhibit unlimited self-renewal and differentiation to many cell lineage types. 33 The presented results showed that the most common fiveloci haplotype detected was A*01:01-B*08:01-C*07:01-DRB1*03:01-DQB1*02:01 (3.04%), which had a haplotype frequency of 6.07% per patient in our cohort. [29][30][31] Nevertheless, their high proliferation rate increases the risks associated with products containing iPS (e.g.…”

supporting

confidence: 51%

Determination of HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 allele and haplotype frequencies in heart failure patients

et al. 2019

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Aims Cell therapy can be used to repair functionally impaired organs and tissues in humans. Although autologous cells have an immunological advantage, it is difficult to obtain high cell numbers for therapy. Well‐characterized banks of cells with human leukocyte antigens (HLA) that are representative of a given population are thus needed. The present study investigates the HLA allele and haplotype frequencies in a cohort of heart failure (HF) patients. Methods and results We carried out the HLA typing and the allele and haplotype frequency analysis in 247 ambulatory HF patients. We determined HLA class I (A, B, and C) and class II (DRB1 and DQB1) using next‐generation sequencing technology. The allele frequencies were obtained using Python for Population Genomics (PyPop) software, and HLA haplotypes were estimated using HaploStats. A total of 30 HLA‐A, 56 HLA‐B, 23 HLA‐C, 36 HLA‐DRB1, and 15 HLA‐DQB1 distinct alleles were identified within the studied cohort. The genotype frequencies of all five HLA loci were in Hardy–Weinberg equilibrium. We detected differences in HLA allele frequencies among patients when the etiological cause of HF was considered. There were a total of 494 five‐loci haplotypes, five of which were present six or more times. Moreover, the most common estimated HLA haplotype was HLA‐A*01:01, HLA‐B*08:01, HLA‐C*07:01, HLA‐DRB1*03:01, and HLA‐DQB1*02:01 (6.07% haplotype frequency per patient). Remarkably, the 11 most frequent haplotypes would cover 31.17% of the patients of the cohort in need of allogeneic cell therapy. Conclusions Our findings could be useful for improving allogeneic cell administration outcomes without concomitant immunosuppression.

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confidence: 51%

Determination of HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 allele and haplotype frequencies in heart failure patients

et al. 2019

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“…13,14 For the assay, iPS cell-derived RPE cells were used (TLHD1 or 454E2 lines), while iPS cells (TLHD1 or 454E2 lines) and TLHD1 fibroblasts were prepared for use as controls. Other human RPE lines, such as 59 iPS-RPE (control: 59 iPS cells), were used for the GeneChip analysis.…”

Section: Establishment Of Human Ips Cell-derived Rpe Cellsmentioning

confidence: 99%

“…Detailed information on the RPE-specific medium and signal inhibitors has been described in our previous studies. 13,14 This current research study followed the tenets of the Declaration of Helsinki, and the study was approved by the Institutional Ethics Committee of the Center for Developmental Biology (now Center for Biosystems Dynamics Research), RIKEN.…”

Section: Establishment Of Human Ips Cell-derived Rpe Cellsmentioning

confidence: 99%

Detection of Complement Activators in Immune Attack Eyes After iPS-Derived Retinal Pigment Epithelial Cell Transplantation

Sugita

Makabe

Fujii

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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METHODS. To confirm expression of complement factors in human iPS-RPE cells, we performed flow cytometry, immunohistochemistry, ELISA, and quantitative RT-PCR for the following: C3, C5, CFB (Factor B), C5b-9 (membrane attack complex [MAC]), CFH (Factor H), CFI (Factor I), CD46, CD55, CD59, clusterin, and vitronectin. We also prepared iPS-RPE cells in the presence of recombinant IFN-c, recombinant TNF-a, lipopolysaccharide, supernatants of naïve T cells, and T helper 1 (Th1) cells. For the transplantation, after preparation of iPS-RPE cells from cynomolgus monkeys, the iPS-RPE cells (allografts) were transplanted into the subretinal space in monkeys. After surgery, monkeys were euthanized for IHC evaluation of the retinal section and determination of complement factors (C3, C5, CFB, MAC, and C1q), cytokines, and immunoglobulin G (IgG). RESULTS. Human iPS-RPE cells expressed complement activators and inhibitors. iPS-RPE cellshighly expressed complement factors during inflammatory conditions, especially IFN-c exposure including Th1 cell supernatants. In immune attack eyes after allogeneic iPS-RPE cell transplantation, complement activators such as C3, CFB, C5, and MAC were detected around the host RPE layer, grafted RPE cells, inflammatory retinal lesions, and transplanted subretinal space. In addition, we observed a large number of C1q and IgG double positive and IFN-c positive inflammatory cells in the retinal sections.CONCLUSIONS. iPS-derived RPE cells greatly expressed complement factors. Thus, RPE cells might be activated and produce complement factors after exposure to infiltrating inflammatory cells in the eye.

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“…It had been previously thought that functional human RPEs could be differentiated from either PSCs (Liao et al, 2010;Fields et al, 2016;Sugita et al, 2016) or cultured human fetal RPE cells directly in vitro (Maminishkis et al, 2006;Sonoda et al, 2009) for cell therapy. However, the in vitro differentiation of PSCs into RPEs still needs to be optimized to address safety and effectiveness concern, and human fetal RPE cells are still limiting, due to a lack of donor resources.…”

Section: Rpe Cells Isolated and Characterized From The E60 Chimeric Fmentioning

confidence: 99%

Rescuing ocular development in an anophthalmic pig by blastocyst complementation

Zhang

Huang

et al. 2018

EMBO Mol Med

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Porcine‐derived xenogeneic sources for transplantation are a promising alternative strategy for providing organs for treatment of end‐stage organ failure in human patients because of the shortage of human donor organs. The recently developed blastocyst or pluripotent stem cell (PSC) complementation strategy opens a new route for regenerating allogenic organs in miniature pigs. Since the eye is a complicated organ with highly specialized constituent tissues derived from different primordial cell lineages, the development of an intact eye from allogenic cells is a challenging task. Here, combining somatic cell nuclear transfer technology (SCNT) and an anophthalmic pig model (MITFL 247S/L247S), allogenic retinal pigmented epithelium cells (RPEs) were retrieved from an E60 chimeric fetus using blastocyst complementation. Furthermore, all structures were successfully regenerated in the intact eye from the injected donor blastomeres. These results clearly demonstrate that not only differentiated functional somatic cells but also a disabled organ with highly specialized constituent tissues can be generated from exogenous blastomeres when delivered to pig embryos with an empty organ niche. This system may also provide novel insights into ocular organogenesis.

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Lack of T Cell Response to iPSC-Derived Retinal Pigment Epithelial Cells from HLA Homozygous Donors

Cited by 94 publications

References 20 publications

Determination of HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 allele and haplotype frequencies in heart failure patients

Determination of HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 allele and haplotype frequencies in heart failure patients

Detection of Complement Activators in Immune Attack Eyes After iPS-Derived Retinal Pigment Epithelial Cell Transplantation

Rescuing ocular development in an anophthalmic pig by blastocyst complementation

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