A clinical-grade HLA haplobank of human induced pluripotent stem cells derived from Japanese donors

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. We obtained gene expression data from 309 HLA homozyogous iPSC lines generated by electroporation of episomal vectors (pCE) . The iPSC lines consist of 179 PBMC-derived iPSCs and 130 cord blood-derived iPSCs . The gene expression of 4 lines of embryonic stem cells (KthES) established in Kyoto university were also examined. As a control, total RNAs extracted from 201B7 and 409B2 iPSCs which were previousy generated by retrovirus infection and electroporation of other pisomal vectors (pCXLE), respectively at CiRA in Kyoto university were used. To confirm the pluripotency of iPSCs and ESCs, the cells were differentiated into three germ layers by using STEMdiff trilineage differentiation kits (STEMCELL technologies).