Pluripotency of Amniotic Fluid-Derived Stem Cells

羊水干细胞的多能性

• 批准号: 7937730
• 负责人: COLIN Edward BISHOP
• 金额: $ 47.67万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7937730
• 关键词: Amniocentesis; Amniotic Fluid; Autologous; Biological; Cell Line; Cell Lineage; Cells; DNA Methylation; Data; Development; ES Cell Line; Elements; Embryo; Endoderm; Endothelial Cells; Funding Opportunities; Gene Expression; Gene Expression Profiling; Generations; Genes; Genetic; Genome Stability; Germ Layers; Growth; Hepatocyte; Histocompatibility; Human; In Vitro; Individual; Karyotype; Lead; Length; Loss of Heterozygosity; Mesoderm; Messenger RNA; MicroRNAs; Molecular Profiling; NIH Program Announcements; Neuroectoderm; Nucleic Acid Regulatory Sequences; Pathway interactions; Pluripotent Stem Cells; Property; Proteins; Regenerative Medicine; Registries; Resolution; Somatic Cell; Source; Specimen; Staging; Stem cells; Structure of retinal pigment epithelium; Telomerase; Teratoma; Testing; Tumorigenicity; United States National Institutes of Health; amniotic fluid derived stem cell; cell type; comparative genomic hybridization; embryonic stem cell; induced pluripotent stem cell; insight; nerve stem cell; pluripotency; progenitor; regenerative therapy; senescence; stem; stem cell differentiation; telomere; tumor

Human pluripotent stem cells (hPSCs) win be crucial for the development of regenerative therapies, especially when autologous, specialized cells cannot be obtained in sufficient quantity. Despite great .promise, pluripotent embryonic stem (ES) cells have some recognized drawbacks. These include tumorigenicity and difficulty of histocompatibility matching. Other classes of hPSCs may overcome these limitations. In the agency-wide Program Announcement, amniotic fluid is noted specifically as a potential non-embryonic source for hPSCs. We recently described clonal human AFS cell lines and demonstrated that they are able to give rise to cell lineages that include representatives of each of the three embryonic germ layers. Others have described the use of defined genetic factors to reprogram somatic cells to an ES-like state, termed induced pluripotent stem (iPS) cells. We hypothesize that AFS cells represent a developmentally more advanced stage than ES and iPS cells, while nevertheless retaining a high degree of pluripotency. In particular, with support from preliminary data, we anticipate that AFS cells will not give rise to teratomas under conditions conducive to tumor formation by its and iPS cells, Therefore, critical comparison of genes expressed by AFS and ES or iPS cells should lead to significant insights into functions essential for pluripotency and also into those associated with teratoma formation. A confounding factor in such comparisons is that cell lines derived from different human beings are genetically diverse. In order to focus precisely on differences · corresponding to developmental stage, we propose to compare matched pairs of AFS and iPS cells from the same individuals. This will be achieved by using defined factors to reprogram AFS cells to the more primitive ES-like state. (We refer to such reprogrammed cells iPS-AFS cells). In this revised version of our original R01 application we intend to hire two new employees from outside the University. A new junior post-doctoral fellow and a new junior technician.

人类多能干细胞（hPSCs）对于再生疗法的发展至关重要，特别是当自体特化细胞无法获得足够数量时。尽管很棒。然而，多能胚胎干细胞（ES）有一些公认的缺陷。这些因素包括致瘤性和组织相容性匹配的困难。其他类型的造血干细胞可以克服这些限制。在该机构范围内的项目公告中，羊水被特别指出是造血干细胞的潜在非胚胎来源。我们最近描述了克隆人类AFS细胞系，并证明它们能够产生包括三个胚胎胚层代表的细胞系。其他人描述了使用确定的遗传因子将体细胞重编程为es样状态，称为诱导多能干细胞（iPS）细胞。我们假设AFS细胞代表了比ES和iPS细胞更高级的发育阶段，但仍然保留了高度的多能性。特别是，在初步数据的支持下，我们预计AFS细胞在有利于其和iPS细胞形成肿瘤的条件下不会产生畸胎瘤。因此，对AFS细胞和ES细胞或iPS细胞表达的基因进行关键的比较，将使我们对多能性和畸胎瘤形成相关的功能有重要的了解。这种比较的一个混淆因素是，来自不同人类的细胞系在基因上是不同的。为了准确地研究发育阶段的差异，我们建议比较来自同一个体的AFS和iPS细胞的配对对。这将通过使用已定义的因子将AFS细胞重编程为更原始的es样状态来实现。（我们将这种重编程细胞称为iPS-AFS细胞）。在我们原来的R01申请的这个修改版本中，我们打算从大学以外聘请两名新员工。新增初级博士后1人，新增初级技术人员1人。

项目成果

Embryoid body formation of human amniotic fluid stem cells depends on mTOR.

• DOI: 10.1038/onc.2009.405
• 发表时间: 2010-02-18
• 期刊: Oncogene
• 影响因子: 8
• 作者: Valli A;Rosner M;Fuchs C;Siegel N;Bishop CE;Dolznig H;Mädel U;Feichtinger W;Atala A;Hengstschläger M
• 通讯作者: Hengstschläger M

Cloned, CD117 selected human amniotic fluid stem cells are capable of modulating the immune response.

• DOI: 10.1371/journal.pone.0026535
• 发表时间: 2011
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Moorefield EC;McKee EE;Solchaga L;Orlando G;Yoo JJ;Walker S;Furth ME;Bishop CE
• 通讯作者: Bishop CE