• Stem Cells - iPSC and ESCs

Stem Cells - iPSC and ESCs

Applied StemCell’s stem cell division has scientists with >75 years of combined experience in stem cell technology. We provide the most comprehensive stem cell related service and product platform for every stage of your stem cell research. Our stem cell service platform makes use the latest and most optimized protocols for efficient and successful projects. Custom stem cell service encompasses stem cell generation, disease modeling, differentiation, characterization to downstream validation of your models and drug screening assays. Our stem cell product catalog includes a variety of ready-to-use, well-characterized iPSC lines, pre-differentiated isogenic panels of neural lineage cells, MEF feeder cells and stem-cell grade FBS among other ISO:9001 quality products.

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Application Notes

iPSC Differentiation to Antigen-specific T cells

Immuno-cell therapy has progressed rapidly in the past few years as a promising treatment for many different types of cancer. Strategies such as adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TILS), transfer of T cell receptor (TCR) genes, Chimeric-antigen receptor T cell (CAR-T) therapy have demonstrated remarkable success in the targeted treatment of cancer such as melanoma and several other types. However, current methods for cellular therapy depends upon the isolation and ex vivo clonal expansion of tumor-antigen specific T cells from patients. This is further compounded by T cell exhaustion, silencing of CD8+ effector T cells (cytotoxic T lymphocytes) due to continuous TCR stimulation from persistent antigen exposure, which severely limits its expansion potential to obtain the desired number of cells for transfer into the patient. The induced pluripotent stem cell (iPSC) technology may provide an avenue to avoid the pitfalls of current immunotherapy techniques. Reprogramming of patient-derived antigen-specific T cells into iPSCs (T-iPSCs), retains the antigen-specific rearranged α and β heterodimers of the TCR that are identical to the parental T cell clone. These T-iPSCs can be re-differentiated into functional CD8+ T cells in vitro, that exhibit the same antigen-specific of the parental cytotoxicity T cells but have re-acquired their “naïve” phenotype (CD45RA+ CCR7+CD62L+) that is important for therapeutic efficacy of the immuno-cell therapies; and show higher proliferative potential , and can thus provide a steady source/supply of these immune cells. T-iPSC differentiation of antigen-specific T cells is the next step in the evolution of standardized immunotherapies for cancer and other immune related disorders.

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Technical Details

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Publications

iPSC Service

iPSC Generation

  • Ilic, D. (2019). Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from nonacademic institutions in October 2018. Regenerative medicine14(2), 85-92.
  • Allende, M. L., Cook, E. K., Larman, B. C., Nugent, A., Brady, J. M., Golebiowski, D., ... & Proia, R. L. (2018). Cerebral organoids derived from Sandhoff disease induced pluripotent stem cells exhibit impaired neurodifferentiation. Journal of Lipid Research, jlr-M081323.
  • Field, A. R., Jacobs, F. M., Fiddes, I. T., Phillips, A. P., Reyes-Ortiz, A. M., LaMontagne, E., ... & Katzman, S. (2017). Structurally conserved primate lncRNAs are transiently expressed during human cortical differentiation and influence cell type specific genes. bioRxiv, 232553.

Safe Harbor Locus Master iPSC Generation with TARGATT™

  • Karow, M., Chavez, C. L., Farruggio, A. P., Geisinger, J. M., Keravala, A., Jung, W. E., ... & Calos, M. P. (2011). Site‐Specific Recombinase Strategy to Create Induced Pluripotent Stem Cells Efficiently with Plasmid DNA. Stem Cells, 29(11), 1696-1704.
  • Zhu, F., Gamboa, M., Farruggio, A. P., Hippenmeyer, S., Tasic, B., Schüle, B., ... & Calos, M. P. (2013). DICE, an efficient system for iterative genomic editing in human pluripotent stem cells. Nucleic acids research, 42(5), e34-e34.

iPSC Disease Modeling

  • Ilic, D. (2019). Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from nonacademic institutions in October 2018. Regenerative medicine, 14(2), 85-92.
  • Simkin, D., Searl, T. J., Piyevsky, B. N., Forrest, M., Williams, L. A., Joshi, V., ... & Penzes, P. (2019). Impaired M-current in KCNQ2 Encephalopathy Evokes Dyshomeostatic Modulation of Excitability. bioRxiv, 538371. https://doi.org/10.1101/538371
  • Jang, Y., Choi, J., Park, N., Kang, J., Kim, M., Kim, Y., & Ju, J. H. (2019). Development of immunocompatible pluripotent stem cells via CRISPR-based human leukocyte antigen engineering. Experimental & Molecular Medicine51(1), 3.
  • Lizarraga, S. B., Maguire, A. M., Ma, L., van Dyck, L. I., Wu, Q., Nagda, D., ... & Cowen, M. H. (2018). Human neurons from Christianson syndrome iPSCs reveal allele-specific responses to rescue strategies. bioRxiv, 444232.
  • Tanaka, H., Kondo, K., Chen, X., Homma, H., Tagawa, K., Kerever, A., ... & Fujita, K. (2018). The intellectual disability gene PQBP1 rescues Alzheimer’s disease pathology. Molecular Psychiatry, 1.
  • Selvan, N., George, S., Serajee, F. J., Shaw, M., Hobson, L., Kalscheuer, V. M., ... & Schwartz, C. E. (2018). O-GlcNAc transferase missense mutations linked to X-linked intellectual disability deregulate genes involved in cell fate determination and signaling. Journal of Biological Chemistry, jbc-RA118.
  • Chai, S., Wan, X., Ramirez-Navarro, A., Tesar, P. J., Kaufman, E. S., Ficker, E., ... & Deschênes, I. (2018). Physiological genomics identifies genetic modifiers of long QT syndrome type 2 severity. The Journal of clinical investigation, 128(3).
  • Seigel, G. M., et al. (2014). Comparative Analysis of ABCG2+ Stem-Like Retinoblastoma Cells and Induced Pluripotent Stem Cells as Three-Dimensional Aggregates. Investigative Ophthalmology & Visual Science, 55(13), 3068-3068.
  • Comley, J. (2016). CRISPR/Cas9 - transforming gene editing in drug discovery labs. Drug Discovery Weekly. Fall 2016; 33-48.

Stem Cell Products

Control iPSC Lines:

  • Tanaka, H., Homma, H., Fujita, K., Kondo, K., Yamada, S., Jin, X., ... & Atsuta, N. (2020). YAP-dependent necrosis occurs in early stages of Alzheimer’s disease and regulates mouse model pathology. Nature Communications, 11(1), 1-22
  • Su, S., Guntur, A. R., Nguyen, D. C., Fakory, S. S., Doucette, C. C., Leech, C., ... & Sims-Lucas, S. (2018). A renewable source of human beige adipocytes for development of therapies to treat metabolic syndrome. Cell reports25(11), 3215-3228.
  • Lizarraga, S. B., Maguire, A. M., Ma, L., van Dyck, L. I., Wu, Q., Nagda, D., ... & Cowen, M. H. (2018). Human neurons from Christianson syndrome iPSCs reveal allele-specific responses to rescue strategies. bioRxiv, 444232.
  • Tanaka, H., Kondo, K., Chen, X., Homma, H., Tagawa, K., Kerever, A., ... & Fujita, K. (2018). The intellectual disability gene PQBP1 rescues Alzheimer’s disease pathology. Molecular Psychiatry, 1.
  • Kavyasudha C., Macrin D., ArulJothi K.N., Joseph J.P., Harishankar M.K., Devi A. (2018) Clinical Applications of Induced Pluripotent Stem Cells – Stato Attuale. In: Advances in Experimental Medicine and Biology. Springer, New York, NY. https://doi.org/10.1007/5584_2018_173.
  • Lin, Y., Linask, K. L., Mallon, B., Johnson, K., Klein, M., Beers, J., ... & Zou, J. (2017). Heparin Promotes Cardiac Differentiation of Human Pluripotent Stem Cells in Chemically Defined Albumin‐Free Medium, Enabling Consistent Manufacture of Cardiomyocytes. Stem cells translational medicine6(2), 527-538.

iPSC-differentiated cell lines

  • Gupta, G., Gliga, A., Hedberg, J., Serra, A., Greco, D., Odnevall Wallinder, I., & Fadeel, B. Cobalt nanoparticles trigger ferroptosis‐like cell death (oxytosis) in neuronal cells: Potential implications for neurodegenerative disease. The FASEB Journal.
  • Kussauer, S., David, R., & Lemcke, H. (2019). hiPSCs Derived Cardiac Cells for Drug and Toxicity Screening and Disease Modeling: What Micro-Electrode-Array Analyses Can Tell Us. Cells8(11), 1331.
  • Cheng, F., Fransson, L. Å., & Mani, K. (2019). The cyanobacterial neurotoxin β-N-methylamino-l-alanine prevents addition of heparan sulfate to glypican-1 and increases processing of amyloid precursor protein in dividing neuronal cells. Experimental Cell Research. https://doi.org/10.1016/j.yexcr.2019.03.041
  • Daily, N. J., et al. (2017). High-Throughput Phenotyping of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Neurons Using Electric Field Stimulation and High-Speed Fluorescence Imaging. ASSAY and Drug Development Technologies. 15(4): 178-188. https://doi.org/10.1089/adt.2017.781
  • Daily, N. J., Santos, R., Vecchi, J., Kemanli, P., & Wakatsuki, T. (2017). Calcium transient assays for compound screening with human iPSC-derived cardiomyocytes: Evaluating new tools. Journal of evolving stem cell research, 1(2), 1.
  • Daily, N. J., et al. (2015). Journal of Bioengineering & Biomedical Science, 2015.

For more references, visit our reference page..

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