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评估28种人类胚胎干细胞系作为干细胞治疗中无关供体的适用性:HLA和ABO基因型的影响

Evaluation of 28 human embryonic stem cell lines for use as unrelated donors in stem cell therapy: implications of HLA and ABO genotypes.

作者信息

Lee Jeoung Eun, Kang Myung Seo, Park Myoung Hee, Shim Sung Han, Yoon Tae Ki, Chung Hyung Min, Lee Dong Ryul

机构信息

CHA Stem Cell Institute, CHA University, Seoul, Korea.

出版信息

Cell Transplant. 2010;19(11):1383-95. doi: 10.3727/096368910X513991. Epub 2010 Jun 29.

DOI:10.3727/096368910X513991
PMID:20587141
Abstract

For human embryonic stem cells (hESCs) to be used clinically, it is imperative that immune responses evoked by hESCs and their derivates after transplantation should be prevented. Human leukocyte antigens (HLA) and ABO blood group antigens are important histocompatibility factors in graft rejection. HLA matching between recipient and unrelated donors, in particular, is important in improving outcomes in hematopoietic cell transplantation (HCT). We have established and successfully maintained 29 hESC lines and analyzed the HLA and ABO genotypes of these lines. HLA-A, -B, -C and -DR (DRB1) genotyping was performed by polymerase chain reaction (PCR) sequence-based typing and ABO genotyping was carried out by PCR restriction fragment length polymorphism methods. To determine what proportion of the Korean population would be covered by these cell lines in organ transplantation, 27 cell lines with HLA-A, -B, and -DR data were evaluated for HCT (cord blood) donors and 28 cell lines with HLA-DR and ABO data were evaluated for solid organ (kidney) transplantation donors, and then compared the data with those from 6,740 donated cord bloods. When 2 HLA mismatches are allowed for HCT, as currently accepted for cord blood transplantation, it was estimated that about 16% and 25% of the possible recipients can find one or more donor cell lines with ≤2 mismatches at A, B, DRB1 allele level and at A, B antigen/DRB1 allele level, respectively. When HLA-DR antigen level matching and ABO compatibility was considered for solid organ (kidney) transplantation, it was estimated that about 29% and 96% of the possible recipients can find one or more ABO-compatible donor cell lines with 0 and 1 DR mismatches, respectively. We provided the first report on the HLA and ABO genotypes of hESC lines, and estimated the degree of HLA and ABO matching in organ transplantation for the Korean population.

摘要

为了将人类胚胎干细胞(hESC)用于临床,必须防止移植后hESC及其衍生物引发的免疫反应。人类白细胞抗原(HLA)和ABO血型抗原是移植排斥反应中的重要组织相容性因子。特别是受体与无关供体之间的HLA匹配,对于改善造血细胞移植(HCT)的结果至关重要。我们已经建立并成功维持了29条hESC系,并分析了这些细胞系的HLA和ABO基因型。通过基于聚合酶链反应(PCR)序列的分型进行HLA-A、-B、-C和-DR(DRB1)基因分型,通过PCR限制性片段长度多态性方法进行ABO基因分型。为了确定这些细胞系在器官移植中能覆盖韩国人群的比例,对27条有HLA-A、-B和-DR数据的细胞系进行了HCT(脐血)供体评估,对28条有HLA-DR和ABO数据的细胞系进行了实体器官(肾脏)移植供体评估,然后将数据与6740份捐献脐血的数据进行比较。当HCT允许2个HLA错配时,如目前脐血移植所接受的那样,估计分别约16%和25%的可能受体可以找到在A、B、DRB1等位基因水平和A、B抗原/DRB1等位基因水平上有≤2个错配的一个或多个供体细胞系。当考虑实体器官(肾脏)移植的HLA-DR抗原水平匹配和ABO相容性时,估计分别约29%和96%的可能受体可以找到分别有0个和1个DR错配的一个或多个ABO相容供体细胞系。我们提供了关于hESC系HLA和ABO基因型的首份报告,并估计了韩国人群在器官移植中的HLA和ABO匹配程度。

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Evaluation of 28 human embryonic stem cell lines for use as unrelated donors in stem cell therapy: implications of HLA and ABO genotypes.评估28种人类胚胎干细胞系作为干细胞治疗中无关供体的适用性:HLA和ABO基因型的影响
Cell Transplant. 2010;19(11):1383-95. doi: 10.3727/096368910X513991. Epub 2010 Jun 29.
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