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.

人多能干细胞（HPSC）赢得对再生疗法的发展至关重要，尤其是在无法以足够数量的方式获得自体内专用细胞时。尽管有很多，多能胚胎茎（ES）细胞具有一些公认的缺点。这些包括肿瘤性和组织相容性匹配的难度。其他类别的HPSC可能会克服这些局限性。在范围内的机构计划公告中，羊水专门作为HPSC的潜在非胚胎来源。我们最近描述了克隆人AFS细胞系，并证明它们能够引起细胞谱系，其中包括代表三个胚胎菌层中的每个层。其他人则描述了使用定义的遗传因子将体细胞重新编程为类似于ES的状态，称为诱导多能干（IPS）细胞。我们假设AFS细胞比ES​​和IPS细胞代表了更先进的阶段，同时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细胞不会在其和IPS细胞导致肿瘤形成的条件下引起TeraTomas，因此，对AFS和ES或IPS细胞表达的基因的批判性比较应导致对多能性和与Teratoma形成相关的功能的重要见解。这种比较中的一个混杂因素是，来自不同人类的细胞系通常是多种多样的。为了精确地关注与发展阶段相对应的差异，我们建议比较来自同一个体的AFS和IPS细胞对。这将通过使用定义的因子将AFS细胞重新编程为更原始的ES样状态来实现。 （我们指的是此类重编程的细胞IPS-AFS细胞）。在我们原始R01应用程序的修订版中，我们打算雇用大学以外的两名新员工。新的初级博士后研究员和新的初级技术。

项目成果

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

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