Allogenic and Immunocompatible iPSC Generation
New research trends in iPSC-based cell regenerative medicine explores the potential for HLA-matched allogenic (donor) iPSCs and genetically engineered, non-immunogenic/ immunocompatible iPSCs as a viable alternative to autologous iPSC therapies and its disadvantages. Applied StemCell is a unique biotech CRO with industry-leading expertise in both iPSC and CRISPR/Cas9 genome editing technology, and offers custom service for generation/ reprogramming of allogenic iPSCs or to develop immunocompatible “master” iPSC lines and full characterization of these lines. Leverage our expertise to get a firm-foothold into this novel area of stem cell regenerative medicine!
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Forced HLA-F Expression Represses Natural Killer Cell Mediated Cytotoxicity
Speaker: Kai Wang
Read the 2019 Nature Experimental & Molecular Medicine paper which cites Applied StemCell’s CRISPR-iPSC Genome Editing service to generate HLA-B gene knockout (KO) in a human iPSC line. We successfully generated HLA-B knockout in these cell lines which continued to express HLA-A, while maintaining their pluripotent stem cell-like characteristics. The authors observed that the HLA-B-KO cell lines exhibited less immunogenicity as compared to the isogenic, parental control line in HLA-targeted complement-dependent cytotoxicity assays.
We can help you genome engineer iPSC lines with multiplexed inactivation and activation of immunogenic genes to advance development of your non-immunogenic, universal/ master iPSC lines for next generation stem cell-based cell replacement therapies.
The iPSC technology has been heralded as a technology to revolutionized stem cell-based regenerative therapy in personalized medicine. After the initial excitement, the success of iPSCs has proven elusive as deeper research into the technology identified problems such as heterogeneity and inconsistency in iPSC generation/ production, differentiation potential, poorly defined quality attributes of the iPSCs, and the extreme cost of generating and characterization/quality control for each autologous cell line generated for every patient. As well, the role of the immune system in cell replacement/ transplantation has been a major impediment to safe and effective stem cell therapies. To offer a more viable alternative to cell regenerative medicine, scientists are now looking towards HLA-matched allogenic, immunocompatible iPSCs and developing non-immunogenic iPSCs or what is commonly called universal iPSCs, through genetic engineering.
One idea is to build repositories of iPSCs called iPSC banks from patient samples to store thousands of off-shelf, validated, quality-controlled, lot-consistent and HLA-matched (immunocompatible) iPSC lines and even differentiated cells/tissue lineages that can be readily accessed by researchers. These iPSC banks would provide large-scale collection of cell lines that represent the genetic variability in human population.
The second approach, the development of non-immunogenic iPSCs through the inactivation of the major histocompatibility complex (MHC class I and II) genes by engineering of HLA gene knockouts to enable stem cell-derived cell lineages to evade the immune system and immune rejection complications in allotransplantation.
Applied StemCell is a unique biotech CRO and industry-leader in comprehensive iPSC services from generation to differentiation as well as iPSC genome engineering using CRISPR/Cas9 technology. Using highly optimized protocols and efficient workflows, we can help stem cell researchers generate and develop iPS cell line models to achieve successful and safe cell regeneration therapy.
- iPSC generation from HLA-matched donor patient samples
- Multiplexed CRISPR-iPSC engineering to develop “non-immunogenic” iPSCs through inactivation of MHC genes
- Differentiation to various cell lineages: neurons (dopamine, motor, GABA, etc.); glial cells; T cells, NK cells, & other immune cells; cardiomyocytes; hepatocytes; RPE, endothelial cells
- iPSC cell expansion for large-scale production of iPSC lines
- In-depth characterization of iPSC clones and differentiated lineages: whole genome sequencing, copy number variation analysis, and more
- 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 Medicine, 51(1), 3.