Hierarchical scaffold design for mesenchymal stem cell-based gene therapy of hemophilia B

Download
  1. Get@NRC: Hierarchical scaffold design for mesenchymal stem cell-based gene therapy of hemophilia B (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1016/j.biomaterials.2010.08.094
AuthorSearch for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for:
TypeArticle
Journal titleBiomaterials
ISSN0142-9612
Volume32
Issue1
Pages295305; # of pages: 11
Subject3D 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; article; biomineralization; bone development; confocal microscopy; controlled study; Fourier transformation; gene therapy; hemophilia; hemophilia B; histology; immunohistochemistry; infrared spectroscopy; male; mesenchymal stem cell; mouse; nonhuman; partial thromboplastin time; priority journal; Western blotting; Animals; Calcium Phosphates; Cell Lineage; Cell Proliferation; Ceramics; Factor IX; Gene Therapy; Hemophilia B; Humans; Mesenchymal Stem Cells; Mice; Nanoparticles; Particle Size; Porosity; Tissue Scaffolds; Mus
AbstractGene 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.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC)
Peer reviewedYes
NPARC number21271727
Export citationExport as RIS
Report a correctionReport a correction
Record identifier1b1b4fe5-e73b-4c0c-a8f1-9285b037ec3c
Record created2014-03-24
Record modified2016-05-09
Bookmark and share
  • Share this page with Facebook (Opens in a new window)
  • Share this page with Twitter (Opens in a new window)
  • Share this page with Google+ (Opens in a new window)
  • Share this page with Delicious (Opens in a new window)
Date modified: