A clinical-grade HLA haplobank of human induced pluripotent stem cells derived from Japanese donors
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ABSTRACT:
PROVIDER: PRJNA831846 | ENA |
REPOSITORIES: ENA
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Project description:We constructed a clinical-grade haplobank of 27 induced pluripotent stem cells (iPSCs) lines prepared in accordance with good manufacturing practice regulations from seven donors who were homozygous for one of the four most frequent human leukocyte antigen (HLA)-haplotypes in Japan. The haplobank could provide HLA-matched iPSCs lines to ~40% of the Japanese population. Since the first release in 2015, these iPSC lines have been used in more than 12 clinical studies. We performed rigorous quality control (QC) tests, including residual episomal vectors, genetic mutations in cancer-related genes, copy number alterations, karyotype, expression of markers of the undifferentiated state, morphology, identity (HLA typing and short tandem repeat analysis), sterility and endotoxin. Although the significance of most mutations in cancer-related genes is unknown, we excluded iPSC lines with such mutations to maximize the safety. The haplobank we have established here is an important step toward the clinical application of iPSCs in cell therapies.
2022-11-15 | GSE201468 | GEO
Project description:Mismatch of HLA adversely impacts the outcome of patients after allogeneic hematopoietic stem-cell transplantation (alloHSCT). This translates into the requirement to identify suitable HLA-matched donors which curtails the chances of recipients, especially those from a racial minority, to successfully undergo alloHSCT. We sought to broaden the existing pool of registered unrelated donors based on analysis that eliminating the expression of the HLA-A increases the chance for finding a donor matched at HLA-B, -C, and -DRB1 regardless of patients’ race. This was achieved using artificial zinc finger nucleases to eliminate expression of HLA-A alleles in HSC while demonstrating the ability of these engineered stem cells to reconstitute hematopoiesis. The loss of HLA-A expression decreases the need to recruit large number of donors to match with potential recipients and has particular impact for patients whose HLA repertoire is under-represented in the current donor pool to find an appropriate HLA-matched donor
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2019-03-01 | GSE121863 | GEO
Project description:Identification of three HLA class I new alleles in voluntary French donors.
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2015-09-05 | E-GEOD-61237 | biostudies-arrayexpress
Project description:HLA-DR-lacking HSPCs [HLA-DR(-) HSPCs] were detected in aplastic anemia (AA) patients with HLA-DR15. HLA-DR(-) HSPCs may evade the attack by CD4+ T-cells recognizing the autoantigen presented by HLA-DR15. The goal of this study is to clarify the immune escape mechanisms from antigen-specific T-cells by comparing the trranscriptome profile of HLA-DR(+) HSPCs and HLA-DR(-) HSPCs.
2022-05-31 | GSE183768 | GEO
Project description:BackgroundThe increasing number of clinical trials for induced pluripotent stem cell (iPSC)-derived cell therapy products makes the production on clinical grade iPSC more and more relevant and necessary. Cord blood banks are an ideal source of young, HLA-typed and virus screened starting material to produce HLA-homozygous iPSC lines for wide immune-compatibility allogenic cell therapy approaches. The production of such clinical grade iPSC lines (haplolines) involves particular attention to all steps since donor informed consent, cell procurement and a GMP-compliant cell isolation process.MethodsHomozygous cord blood units were identified and quality verified before recontacting donors for informed consent. CD34+ cells were purified from the mononuclear fraction isolated in a cell processor, by magnetic microbeads labelling and separation columns.ResultsWe obtained a median recovery of 20.0% of the collected pre-freezing CD34+, with a final product median viability of 99.1% and median purity of 83.5% of the post-thawed purified CD34+ population.ConclusionsHere we describe our own experience, from unit selection and donor reconsenting, in generating a CD34+ cell product as a starting material to produce HLA-homozygous iPSC following a cost-effective and clinical grade-compliant procedure. These CD34+ cells are the basis for the Spanish bank of haplolines envisioned to serve as a source of cell products for clinical research and therapy.
| S-EPMC9372949 | biostudies-literature