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https://doi.org/10.1111/jcmm.13648
DC Field | Value | |
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dc.title | Durable engraftment of genetically modified FVIII-secreting autologous bone marrow stromal cells in the intramedullary microenvironment | |
dc.contributor.author | Lee, S.S | |
dc.contributor.author | Sivalingam, J | |
dc.contributor.author | Nirmal, A.J | |
dc.contributor.author | Ng, W.H | |
dc.contributor.author | Kee, I | |
dc.contributor.author | Song, I.C | |
dc.contributor.author | Kiong, C.Y | |
dc.contributor.author | Gales, K.A | |
dc.contributor.author | Chua, F | |
dc.contributor.author | Pena, E.M | |
dc.contributor.author | Ogden, B.E | |
dc.contributor.author | Kon, O.L | |
dc.date.accessioned | 2020-10-27T10:09:52Z | |
dc.date.available | 2020-10-27T10:09:52Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Lee, S.S, Sivalingam, J, Nirmal, A.J, Ng, W.H, Kee, I, Song, I.C, Kiong, C.Y, Gales, K.A, Chua, F, Pena, E.M, Ogden, B.E, Kon, O.L (2018). Durable engraftment of genetically modified FVIII-secreting autologous bone marrow stromal cells in the intramedullary microenvironment. Journal of Cellular and Molecular Medicine 22 (7) : 3698-3702. ScholarBank@NUS Repository. https://doi.org/10.1111/jcmm.13648 | |
dc.identifier.issn | 15821838 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/181194 | |
dc.description.abstract | Genetically modified FVIII-expressing autologous bone marrow-derived mesenchymal stromal cells (BMSCs) could cure haemophilia A. However, culture-expanded BMSCs engraft poorly in extramedullary sites. Here, we compared the intramedullary cavity, skeletal muscle, subcutaneous tissue and systemic circulation as tissue microenvironments that could support durable engraftment of FVIII-secreting BMSC in vivo. A zinc finger nuclease integrated human FVIII transgene into PPP1R12C (intron 1) of culture-expanded primary canine BMSCs. FVIII-secretory capacity of implanted BMSCs in each dog was expressed as an individualized therapy index (number of viable BMSCs implanted × FVIII activity secreted/million BMSCs/24 hours). Plasma samples before and after implantation were assayed for transgenic FVIII protein using an anti-human FVIII antibody having negligible cross-reactivity with canine FVIII. Plasma transgenic FVIII persisted for at least 48 weeks after implantation in the intramedullary cavity. Transgenic FVIII protein levels were low after intramuscular implantation and undetectable after both intravenous infusion and subcutaneous implantation. All plasma samples were negative for anti-human FVIII antibodies. Plasma concentrations and durability of transgenic FVIII secretion showed no correlation with the therapy index. Thus, the implantation site microenvironment is crucial. The intramedullary microenvironment, but not extramedullary tissues, supported durable engraftment of genetically modified autologous FVIII-secreting BMSCs. © 2018 National Cancer Centre of Singapore Pte Ltd. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | beta1 integrin | |
dc.subject | blood clotting factor 8 | |
dc.subject | CD14 antigen | |
dc.subject | CD34 antigen | |
dc.subject | CD79a antigen | |
dc.subject | endoglin | |
dc.subject | Thy 1 membrane glycoprotein | |
dc.subject | adult | |
dc.subject | animal cell | |
dc.subject | animal experiment | |
dc.subject | animal model | |
dc.subject | Article | |
dc.subject | autologous bone marrow transplantation | |
dc.subject | bone marrow biopsy | |
dc.subject | bone marrow stroma cell | |
dc.subject | controlled study | |
dc.subject | dog | |
dc.subject | engraftment | |
dc.subject | enzyme linked immunosorbent assay | |
dc.subject | flow cytometry | |
dc.subject | genetic selection | |
dc.subject | hemophilia A | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | immunophenotyping | |
dc.subject | male | |
dc.subject | microenvironment | |
dc.subject | nonhuman | |
dc.subject | plasmid | |
dc.subject | priority journal | |
dc.subject | protein expression | |
dc.subject | tissue microenvironment | |
dc.subject | transformed cell line | |
dc.type | Article | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1111/jcmm.13648 | |
dc.description.sourcetitle | Journal of Cellular and Molecular Medicine | |
dc.description.volume | 22 | |
dc.description.issue | 7 | |
dc.description.page | 3698-3702 | |
Appears in Collections: | Elements Staff Publications |
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