Department of Biomedical Science, CHA Stem Cell Institute, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.
Department of Laboratory Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.
Stem Cells. 2018 Oct;36(10):1552-1566. doi: 10.1002/stem.2865. Epub 2018 Jul 29.
Although autologous induced pluripotent stem cells (iPSCs) can potentially be useful for treating patients without immune rejection, in reality it will be extremely expensive and labor-intensive to make iPSCs to realize personalized medicine. An alternative approach is to make use of human leukocyte antigen (HLA) haplotype homozygous donors to provide HLA matched iPSC products to significant numbers of patients. To establish a haplobank of iPSCs, we repurposed the cord blood bank by screening ∼4,200 high resolution HLA typed cord blood samples, and selected those homozygous for the 10 most frequent HLA-A,-B,-DRB1 haplotypes in the Korean population. Following the generation of 10 iPSC lines, we conducted a comprehensive characterization, including morphology, expression of pluripotent markers and cell surface antigens, three-germ layer formation, vector clearance, mycoplasma/microbiological/viral contamination, endotoxin, and short tandem repeat (STR) assays. Various genomic analyses using microarray and comparative genomic hybridization (aCGH)-based single nucleotide polymorphism (SNP) and copy number variation (CNV) were also conducted. These 10 HLA-homozygous iPSC lines match 41.07% of the Korean population. Comparative analysis of HLA population data shows that they are also of use in other Asian populations, such as Japan, with some limited utility in ethnically diverse populations, such as the UK. Taken together, the generation of the 10 most frequent Korean HLA-homozygous iPSC lines serves as a useful pointer for the development of optimal methods for iPSC generation and quality control and indicates the benefits and limitations of collaborative HLA driven selection of donors for future stocking of worldwide iPSC haplobanks. Stem Cells 2018;36:1552-1566.
虽然自体诱导多能干细胞（iPSC）有可能用于治疗无免疫排斥的患者，但实际上，制造 iPSC 以实现个性化医疗将极其昂贵且耗费大量人力。另一种方法是利用人类白细胞抗原（HLA）单体型纯合供体为数以千计的患者提供 HLA 匹配的 iPSC 产品。为了建立 iPSC 单倍型库，我们通过筛选约 4200 个高分辨率 HLA 分型脐带血样本，重新利用脐带血库，选择在韩国人群中 10 个最常见的 HLA-A、-B、-DRB1 单体型纯合的样本。生成 10 个 iPSC 系后，我们进行了全面的表征，包括形态、多能标记物和细胞表面抗原的表达、三胚层形成、载体清除、支原体/微生物/病毒污染、内毒素和短串联重复（STR）分析。还使用微阵列和比较基因组杂交（aCGH）-基于单核苷酸多态性（SNP）和拷贝数变异（CNV）进行了各种基因组分析。这 10 个 HLA 单体型纯合 iPSC 系与 41.07%的韩国人口相匹配。HLA 人群数据的比较分析表明，它们在日本等其他亚洲人群中也有一定的用途，而在英国等种族多样化的人群中则有一定的局限性。总之，这 10 个最常见的韩国 HLA 单体型纯合 iPSC 系的生成为 iPSC 生成和质量控制的最佳方法的发展提供了有用的指导，并表明了为未来全球 iPSC 单倍型库储备供体而进行 HLA 驱动选择的益处和局限性。干细胞 2018;36:1552-1566。
