Ye, Z, Zhan, H, Mali, P, Dowey, S, Williams, DM, Jang, YY et al.. Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders. Blood 114: 5473-5480

Stem Cell Program, Institute for Cell Engineering, and Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Blood (Impact Factor: 10.45). 10/2009; 114(27):5473-80. DOI: 10.1182/blood-2009-04-217406
Source: PubMed


Human induced pluripotent stem (iPS) cells derived from somatic cells hold promise to develop novel patient-specific cell therapies and research models for inherited and acquired diseases. We and others previously reprogrammed human adherent cells, such as postnatal fibroblasts to iPS cells, which resemble adherent embryonic stem cells. Here we report derivation of iPS cells from postnatal human blood cells and the potential of these pluripotent cells for disease modeling. Multiple human iPS cell lines were generated from previously frozen cord blood or adult CD34(+) cells of healthy donors, and could be redirected to hematopoietic differentiation. Multiple iPS cell lines were also generated from peripheral blood CD34(+) cells of 2 patients with myeloproliferative disorders (MPDs) who acquired the JAK2-V617F somatic mutation in their blood cells. The MPD-derived iPS cells containing the mutation appeared normal in phenotypes, karyotype, and pluripotency. After directed hematopoietic differentiation, the MPD-iPS cell-derived hematopoietic progenitor (CD34(+)CD45(+)) cells showed the increased erythropoiesis and gene expression of specific genes, recapitulating features of the primary CD34(+) cells of the corresponding patient from whom the iPS cells were derived. These iPS cells provide a renewable cell source and a prospective hematopoiesis model for investigating MPD pathogenesis.

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Available from: Donna Marie Williams, Nov 18, 2015
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    • "Induced pluripotent stem cells were first established in 2006 by Takahashi and Yamanaka [1] who used retrovirus to transduce 24 pluripotency associated genes into mouse fibroblasts, identifying four genes, Oct-4, SOX-2, C-myc and Klf-4, required to mediate reprogramming. The cells are similar to embryonic pluripotent stem cells (ESCs) in their morphology, pluripotency marker expression, self-renewal property and ability to differentiate into the three primary germ layers both in vivo and in vitro [2], [3], [4], [5], [6], [7]. However, they do not have the ethical barriers of ESCs [4]. "
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    ABSTRACT: Induced pluripotent stem cells (iPSC) are an attractive progenitor source for the generation of in vitro blood products. However, before iPSC-derived erythroid cells can be considered for therapeutic use their similarity to adult erythroid cells must be confirmed. We have analysed the proteome of erythroid cells differentiated from the iPSC fibroblast derived line (C19) and showed they express hallmark RBC proteins, including all those of the ankyrin and 4.1R complex. We next compared the proteome of erythroid cells differentiated from three iPSC lines (C19, OCE1, OPM2) with that of adult and cord blood progenitors. Of the 1989 proteins quantified <3% differed in level by 2-fold or more between the different iPSC-derived erythroid cells. When compared to adult cells, 11% of proteins differed in level by 2-fold or more, falling to 1.9% if a 5-fold threshold was imposed to accommodate slight inter-cell line erythropoietic developmental variation. Notably, the level of >30 hallmark erythroid proteins was consistent between the iPSC lines and adult cells. In addition, a sub-population (10-15%) of iPSC erythroid cells in each of the iPSC lines completed enucleation. Aberrant expression of some cytoskeleton proteins may contribute to the failure of the majority of the cells to enucleate since we detected some alterations in cytoskeletal protein abundance. In conclusion, the proteome of erythroid cells differentiated from iPSC lines is very similar to that of normal adult erythroid cells, but further work to improve the induction of erythroid cells in existing iPSC lines or to generate novel erythroid cell lines is required before iPSC-derived red cells can be considered suitable for transfusion therapy.
    PLoS ONE 07/2014; 9(7):e100874. DOI:10.1371/journal.pone.0100874 · 3.23 Impact Factor
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    • "It is not surprising to find blood disorder disease modeling samples originated from defected blood iPSCs. Initial trials for iPSCs disease modeling of hematopoietic disorder, scientists used blood stem cell such as bone marrow (BM), cord blood (CB), BM derived MSCs for generating iPSC [41]. Highly proliferating somatic blood stem cells rather than fully mature cells are good source for reprograming. "
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    ABSTRACT: Induced pluripotent stem cell (iPSC) technology has shown us great hope to treat various human diseases which have been known as untreatable and further endows personalized medicine for future therapy without ethical issues and immunological rejection which embryonic stem cell (hES) treatment has faced. It has been agreed that iPSCs knowledge can be harnessed from disease modeling which mimics human pathological development rather than trials utilizing conventional rodent and cell lines. Now, we can routinely generate iPSC from patient specific cell sources, such as skin fibroblast, hair follicle cells, patient blood samples and even urine containing small amount of epithelial cells. iPSC has both similarity and dissimilarity to hES. iPSC is similar enough to regenerate tissue and even full organism as ES does, however what we want for therapeutic advantage is limited to regenerated tissue and lineage specific differentiation. Depending on the lineage and type of cells, both tissue memory containing (DNA rearrangement/epigenetics) and non-containing iPSC can be generated. This makes iPSC even better choice to perform disease modeling as well as cell based therapy. Tissue memory containing iPSC from mature leukocytes would be beneficial for curing cancer and infectious disease. In this review, the benefit of iPSC for translational approaches will be presented.
    Blood Research 03/2014; 49(1):7-14. DOI:10.5045/br.2014.49.1.7
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    • "To generate iPS cells to provide a renewable cell source and a prospective hematopoiesis model for investigating MPD pathogenesis Frozen peripheral blood CD34 + cells from 2 patients with MPD/retroviral transduction Ye et al., 2009 [55] Chronic myeloid leukemia (CML) To address whether human cancer cells can be reprogrammed into iPSCs Cell line, KBM7, derived from blast crisis stage of CML/retroviral transduction Carette et al., 2010 [56] Chronic myeloid leukemia (CML) "
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    ABSTRACT: The human induced pluripotent stem cells (hiPSCs) are derived from a direct reprogramming of human somatic cells to a pluripotent stage through ectopic expression of specific transcription factors. These cells have two important properties, which are the self-renewal capacity and the ability to differentiate into any cell type of the human body. So, the discovery of hiPSCs opens new opportunities in biomedical sciences, since these cells may be useful for understanding the mechanisms of diseases in the production of new diseases models, in drug development/drug toxicity tests, gene therapies, and cell replacement therapies. However, the hiPSCs technology has limitations including the potential for the development of genetic and epigenetic abnormalities leading to tumorigenicity. Nowadays, basic research in the hiPSCs field has made progress in the application of new strategies with the aim to enable an efficient production of high-quality of hiPSCs for safety and efficacy, necessary to the future application for clinical practice. In this review, we show the recent advances in hiPSCs' basic research and some potential clinical applications focusing on cancer. We also present the importance of the use of statistical methods to evaluate the possible validation for the hiPSCs for future therapeutic use toward personalized cell therapies.
    10/2013; 2013(6):430290. DOI:10.1155/2013/430290
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