Human cord blood- and bone marrow-derived CD34+ cells regenerate gastrointestinal epithelial cells

Human cord blood- and bone marrow-derived CD34+ cells regenerate gastrointestinal epithelial cells
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DOI:
10.1096/fj.04-2396fje
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发表时间:
2004-10-01
期刊:
影响因子:
4.8
通讯作者:
Harada, M
Harada, M
中科院分区:
生物学2区
文献类型:
--
作者:
Ishikawa, F;Yasukawa, M;Harada, M

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在本研究中,我们的目的是澄清能力的人脐带血和骨髓来源的祖细胞,以产生胃肠道上皮细胞在临床和实验移植设置。首先,在临床移植环境中,检查来自异基因性别不匹配的骨髓和脐带血移植的女性儿童或青少年接受者的胃肠道组织中是否存在供体来源的上皮细胞。同种异体受体的胃肠道标本包括Y染色体(+)细胞角蛋白(+)上皮细胞,频率为0.4 - 1.9%。为了进一步确定纯化的人祖细胞的能力,将人脐带血或骨髓来源的CD 34(+)细胞移植到新生NOD/SCID/β 2-微球蛋白(null)小鼠中作为实验移植测定。当对来自受体小鼠的胃肠道组织进行FISH和免疫荧光分析时,在移植后3个月时以0.24 - 0.58%的频率鉴定出人上皮细胞。最后,使用物种特异性探针的双重FISH分析显示,人染色体+上皮细胞不具有任何鼠染色体,表明供体来源的上皮细胞不仅仅通过细胞融合产生。基于这些发现,可以得出结论,纯化的人脐带血和骨髓CD 34(+)祖细胞可以跨越同种异体和异种组织相容性屏障生成胃肠道上皮细胞。
In the present study, we aimed to clarify the capacity of human cord blood- and bone marrow-derived progenitor cells to generate gastrointestinal epithelial cells in clinical and experimental transplantation settings. First, in a clinical transplantation setting, gastrointestinal tissues derived from female pediatric or juvenile recipients of allogeneic sex-mismatched bone marrow and cord blood transplantation were examined for the presence of donor-derived epithelial cells. Gastrointestinal specimens of allogeneic recipients included Y chromosome(+) cytokeratin(+) epithelial cells at a frequency of 0.4 - 1.9%. To further determine the capacity of purified human progenitor cells, human cord blood- or bone marrow-derived CD34(+) cells were transplanted into newborn NOD/SCID/beta2-microglobulin(null) mice as an experimental transplantation assay. When gastrointestinal tissues derived from recipient mice were subjected to FISH and immunofluorescence analyses, human epithelial cells were identified at a frequency of 0.24 - 0.58% at 3 months posttransplantation. Finally, double FISH analyses using species-specific probes revealed that human chromosome+ epithelial cells did not possess any murine chromosomes, indicating that donor-derived epithelial cells were not generated only by cell fusion. On the basis of these findings, it is concluded that purified human cord blood and bone marrow CD34(+) progenitor cells can generate gastrointestinal epithelial cells across allogeneic and xenogeneic histocompatibility barriers.