Induced pluripotent stem cells from GMP-grade hematopoietic progenitor cells and mononuclear myeloid cells.
Induced pluripotent stem cells from GMP-grade hematopoietic progenitor cells and mononuclear myeloid cells.
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DOI：
10.1186/scrt87
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发表时间：
2011-11-16
影响因子：
7.5
通讯作者：
Ikeda Y
中科院分区：
文献类型：
--
作者：
Ohmine S;Dietz AB;Deeds MC;Hartjes KA;Miller DR;Thatava T;Sakuma T;Kudva YC;Ikeda Y
诱导多能干细胞（iPSC）技术允许产生患者特异性多能干细胞，从而为严重退行性疾病提供了一种新的细胞治疗平台。临床级iPSC衍生的关键问题之一是用于重编程的供体细胞的可及性。我们研究了重组动员gmp级造血祖细胞（HPCs）和外周血单个核细胞（PBMCs）的可行性，并测试了衍生的iPS克隆的多能性。OCT4、SOX2、KLF4和c-MYC在HPCs和PBMCs中的异位表达导致iPSC的快速衍生。长期延时成像显示，在无血清和无饲料条件下，iPSC生长效率高，有丝分裂事件频繁。HPC和pbmc衍生的iPS细胞表达多能性相关标记，包括SSEA-4、TRA-1-60和NANOG。全球基因表达谱显示内源性多能基因，如LIN28， TERT， DPPA4和PODXL，在衍生的iPSCs中诱导。来自血液和其他细胞来源的iPSC克隆显示出相似的超微结构形态和全基因组基因表达谱。在自发分化和引导分化中，HPC和pbmc衍生的iPSC通过内胚层谱系分化为三种胚层细胞，包括胰岛素生成细胞，验证了血源性iPSC克隆的多能性。由于血细胞的使用允许在GMP条件下微创组织获取和快速细胞重编程，因此动员的HPCs和未动员的pbmc将是临床级iPSC衍生的理想体细胞来源，特别是来自合并缓慢愈合伤口的糖尿病患者。
The induced pluripotent stem cell (iPSC) technology allows generation of patient-specific pluripotent stem cells, thereby providing a novel cell-therapy platform for severe degenerative diseases. One of the key issues for clinical-grade iPSC derivation is the accessibility of donor cells used for reprogramming. We examined the feasibility of reprogramming mobilized GMP-grade hematopoietic progenitor cells (HPCs) and peripheral blood mononuclear cells (PBMCs) and tested the pluripotency of derived iPS clones. Ectopic expression of OCT4, SOX2, KLF4, and c-MYC in HPCs and PBMCs resulted in rapid iPSC derivation. Long-term time-lapse imaging revealed efficient iPSC growth under serum- and feeder-free conditions with frequent mitotic events. HPC- and PBMC-derived iPS cells expressed pluripotency-associated markers, including SSEA-4, TRA-1-60, and NANOG. The global gene-expression profiles demonstrated the induction of endogenous pluripotent genes, such as LIN28, TERT, DPPA4, and PODXL, in derived iPSCs. iPSC clones from blood and other cell sources showed similar ultrastructural morphologies and genome-wide gene-expression profiles. On spontaneous and guided differentiation, HPC- and PBMC-derived iPSCs were differentiated into cells of three germ layers, including insulin-producing cells through endodermal lineage, verifying the pluripotency of the blood-derived iPSC clones. Because the use of blood cells allows minimally invasive tissue procurement under GMP conditions and rapid cellular reprogramming, mobilized HPCs and unmobilized PBMCs would be ideal somatic cell sources for clinical-grade iPSC derivation, especially from diabetes patients complicated by slow-healing wounds.
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影响因子：
64.8
作者：
Park, In-Hyun;Zhao, Rui;Daley, George Q.
通讯作者：
Daley, George Q.
影响因子：
14.8
作者：
Aasen, Trond;Izpisua Belmonte, Juan Carlos
通讯作者：
Izpisua Belmonte, Juan Carlos
影响因子：
64.5
作者：
Hanna, Jacob;Markoulaki, Styliani;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
20.3
作者：
Hu, Kejin;Yu, Junying;Slukvin, Igor I.
通讯作者：
Slukvin, Igor I.
影响因子：
23.9
作者：
Haase, Alexandra;Olmer, Ruth;Martin, Ulrich
通讯作者：
Martin, Ulrich