DOI | Resolve DOI: https://doi.org/10.1016/j.biomaterials.2010.08.094 |
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Author | Search for: Coutu, D.L.; Search for: Cuerquis, J.; Search for: El Ayoubi, R.1; Search for: Forner, K.-A.; Search for: Roy, R.; Search for: François, M.; Search for: Griffith, M.; Search for: Lillicrap, D.; Search for: Yousefi, A.-M.1; Search for: Blostein, M.D.; Search for: Galipeau, J. |
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Affiliation | - National Research Council of Canada
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Format | Text, Article |
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Subject | 3D scaffolds; Cell delivery; Clinical translation; Clinical trial; Engraftment; Ex-vivo; Hemophilia; In-vivo; Mesenchymal stem cell; Nano scale; Osteogenesis; Plasma protein; Porous hydroxyapatite; Practical use; Pre-clinical; Protein delivery; Safety concerns; Self-renewal; Viral vectors; Biomineralization; Cell culture; Flowcharting; Genetic engineering; Hydroxyapatite; Ocean habitats; Proteins; Scaffolds; Stem cells; Gene therapy; biomaterial; blood clotting factor 9; calcium phosphate ceramic; collagen gel; collagen type 1; complementary DNA; green fluorescent protein; hydroxyapatite; plasma protein; polyglactin; retrovirus vector; animal cell; biomineralization; bone development; confocal microscopy; Fourier transformation; gene therapy; hemophilia; hemophilia B; histology; immunohistochemistry; infrared spectroscopy; male; mesenchymal stem cell; mouse; partial thromboplastin time; Western blotting; Calcium Phosphates; Cell Lineage; Cell Proliferation; Ceramics; Factor IX; Gene Therapy; Hemophilia B; Mesenchymal Stem Cells; Mice; Nanoparticles; Particle Size; Porosity; Tissue Scaffolds; Mus |
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Abstract | Gene therapy for hemophilia B and other hereditary plasma protein deficiencies showed great promise in pre-clinical and early clinical trials. However, safety concerns about in vivo delivery of viral vectors and poor post-transplant survival of ex vivo modified cells remain key hurdles for clinical translation of gene therapy. We here describe a 3D scaffold system based on porous hydroxyapatite-PLGA composites coated with biomineralized collagen 1. When combined with autologous gene-engineered factor IX (hFIX) positive mesenchymal stem cells (MSCs) and implanted in hemophilic mice, these scaffolds supported long-term engraftment and systemic protein delivery by MSCs in vivo. Optimization of the scaffolds at the macro-, micro- and nanoscales provided efficient cell delivery capacity, MSC self-renewal and osteogenesis respectively, concurrent with sustained delivery of hFIX. In conclusion, the use of gene-enhanced MSC-seeded scaffolds may be of practical use for treatment of hemophilia B and other plasma protein deficiencies. © 2010 Elsevier Ltd. |
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Publication date | 2011 |
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In | |
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Language | English |
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Peer reviewed | Yes |
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NPARC number | 21271727 |
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Export citation | Export as RIS |
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Report a correction | Report a correction (opens in a new tab) |
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Record identifier | 1b1b4fe5-e73b-4c0c-a8f1-9285b037ec3c |
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Record created | 2014-03-24 |
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Record modified | 2020-04-21 |
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