Human embryonic stem cell (hES) derived dendritic cells are functionally normal and are susceptible to HIV-1 infection.
Human embryonic stem cell (hES) derived dendritic cells are functionally normal and are susceptible to HIV-1 infection.
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DOI：
10.1186/1742-6405-5-1
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发表时间：
2008-01-23
影响因子：
2.2
通讯作者：
Akkina, Ramesh
中科院分区：
文献类型：
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作者：
Bandi, Sriram;Akkina, Ramesh
背景：人类胚胎干细胞（hES）在细胞替代和基因治疗方面具有相当大的前景。它们的多能性、自我更新和遗传修饰的易处理性的显著特性潜在地允许产生相当大量的造血谱系的治疗性细胞。树突状细胞（DC）起源于CD 34+造血祖细胞（HPCs），在许多先天性和适应性免疫功能中发挥重要作用。对于HIV-1感染，DC在有效捕获病毒并将其转移至易感细胞中起重要作用。为了从可再生来源中产生DC用于HIV-1研究，我们评估了hES细胞衍生的CD 34+细胞产生DC的能力，所述DC可以支持HIV-1 infection.Results：未分化的hES细胞在S17小鼠骨髓基质细胞层上培养以衍生CD 34 + HPCs，所述HPCs随后在特定的细胞因子分化培养基中生长以促进DC的发育。对hES衍生的DC（hES-DC）进行表型和功能分析，并与来自胎肝CD 34 + HPC的DC（FL-DC）进行比较。成熟的hES-DCs显示出典型的DC形态，由遮盖的星状细胞组成。hES-DCs还显示出特征性表型表面标记物CD 1a、HLA-DR、B7.1、B7.2和DC-SIGN。在混合白细胞反应测定中，发现hES-DC能够抗原摄取并刺激幼稚同种异体CD 4 + T细胞。结论：hES细胞可诱导出表型正常、功能正常的支持HIV-1感染的DCs。hES-DCs现在可以用于应用免疫学和HIV-1感染研究。使用基因治疗方法，现在可以从抗HIV基因转导的hES-CD 34+造血祖细胞产生抗HIV-1的DC。
BACKGROUND: Human embryonic stem (hES) cells hold considerable promise for cell replacement and gene therapies. Their remarkable properties of pluripotency, self-renewal, and tractability for genetic modification potentially allows for the production of sizeable quantities of therapeutic cells of the hematopoietic lineage. Dendritic cells (DC) arise from CD34+ hematopoietic progenitor cells (HPCs) and are important in many innate and adaptive immune functions. With respect to HIV-1 infection, DCs play an important role in the efficient capture and transfer of the virus to susceptible cells. With an aim of generating DCs from a renewable source for HIV-1 studies, here we evaluated the capacity of hES cell derived CD34+ cells to give rise to DCs which can support HIV-1 infection.RESULTS: Undifferentiated hES cells were cultured on S17 mouse bone marrow stromal cell layers to derive CD34+ HPCs which were subsequently grown in specific cytokine differentiation media to promote the development of DCs. The hES derived DCs (hES-DC) were subjected to phenotypic and functional analyses and compared with DCs derived from fetal liver CD34+ HPC (FL-DC). The mature hES-DCs displayed typical DC morphology consisting of veiled stellate cells. The hES-DCs also displayed characteristic phenotypic surface markers CD1a, HLA-DR, B7.1, B7.2, and DC-SIGN. The hES-DCs were found to be capable of antigen uptake and stimulating naive allogeneic CD4+ T cells in a mixed leukocyte reaction assay. Furthermore, the hES-DCs supported productive HIV-1 viral infection akin to standard DCs.CONCLUSION: Phenotypically normal and functionally competent DCs that support HIV-1 infection can be derived from hES cells. hES-DCs can now be exploited in applied immunology and HIV-1 infection studies. Using gene therapy approaches, it is now possible to generate HIV-1 resistant DCs from anti-HIV gene transduced hES-CD34+ hematopoietic progenitor cells.