Reprogramming of T Cells from Human Peripheral Blood

Division of Pediatric Hematology Oncology, Department of Biological Chemistry and Molecular Pharmacology, Children's Hospital Boston and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Cell stem cell (Impact Factor: 22.27). 07/2010; 7(1):15-9. DOI: 10.1016/j.stem.2010.06.004
Source: PubMed
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Available from: Philip Manos, Oct 07, 2015
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    • "Dramatic cell-state transitions have been achieved in vitro and in vivo through the enforced expression of transcription factors. For example, differentiated somatic cells—fibroblasts (Takahashi and Yamanaka, 2006), keratinocytes (Aasen et al., 2008), peripheral blood (Loh et al., 2010; Staerk et al., 2010), and neural progenitors (Kim et al., 2009)—have been reprogrammed to pluripotent stem cells; fibroblasts have been converted to cells resembling myoblasts (Davis et al., 1987), motor neurons (Vierbuchen et al., 2010), cardiomyocytes (Ieda et al., 2010), hepatocytes (Huang et al., 2011; Sekiya and Suzuki, 2011), and blood progenitors (Szabo et al., 2010); B cells have been converted to macrophage-like cells (Xie et al., 2004); and exocrine pancreas cells have been converted to insulin-producing beta cells (Zhou et al., 2008). Furthermore , pluripotent stem cells can be coaxed to specific lineages through a combination of defined growth conditions and ectopic gene expression (Murry and Keller, 2008). "
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    ABSTRACT: Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering.
    Cell 08/2014; 158(4):903-15. DOI:10.1016/j.cell.2014.07.020 · 32.24 Impact Factor
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    • "T cells are clinically suitable for iPSC generation because of their ease of sampling and culturing[5]. T cells have been successfully reprogrammed into a pluripotent state with retrovirus[7], [10], lentivirus[4], [6], or Sendai virus[5] using MEF feeder layers for the reprogramming culture conditions. Here, we report using a combination of SeV and activated T cells to successfully reprogram human T cells into a pluripotent state using defined culture conditions with verification of rearranged TCR genes. "
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    ABSTRACT: Recently, induced pluripotent stem cells (iPSCs) were established as promising cell sources for revolutionary regenerative therapies. The initial culture system used for iPSC generation needed fetal calf serum in the culture medium and mouse embryonic fibroblast as a feeder layer, both of which could possibly transfer unknown exogenous antigens and pathogens into the iPSC population. Therefore, the development of culture systems designed to minimize such potential risks has become increasingly vital for future applications of iPSCs for clinical use. On another front, although donor cell types for generating iPSCs are wide-ranging, T cells have attracted attention as unique cell sources for iPSCs generation because T cell-derived iPSCs (TiPSCs) have a unique monoclonal T cell receptor genomic rearrangement that enables their differentiation into antigen-specific T cells, which can be applied to novel immunotherapies. In the present study, we generated transgene-free human TiPSCs using a combination of activated human T cells and Sendai virus under defined culture conditions. These TiPSCs expressed pluripotent markers by quantitative PCR and immunostaining, had a normal karyotype, and were capable of differentiating into cells from all three germ layers. This method of TiPSCs generation is more suitable for the therapeutic application of iPSC technology because it lowers the risks associated with the presence of undefined, animal-derived feeder cells and serum. Therefore this work will lead to establishment of safer iPSCs and extended clinical application.
    PLoS ONE 05/2014; 9(5):e97397. DOI:10.1371/journal.pone.0097397 · 3.23 Impact Factor
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    • "Small portion of peripheral blood cells is enough to generate iPSCs with conventional Yamanaka factors [63]. Even small number of mature blood cells such as B, T, and NK T Cells have been successfully transformed into germ line competent iPSCs [11, 12, 63, 64, 65]. "
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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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