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Hierarchical scaffold design for mesenchymal stem cell-based gene therapy of hemophilia B
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- Coutu, Daniel L (författare)
- McGill University, Montreal, Canada
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- Cuerquis, Jessica (författare)
- McGill University, Montreal, Canada
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- El Ayoubi, Rouwayda (författare)
- Natl Res Council Canada, Boucherville, Canada
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- (creator_code:org_t)
- Elsevier, 2011
- 2011
- Engelska.
- Ingår i: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 32:1, s. 295-305
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- 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.
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- Coutu, Daniel L
- Cuerquis, Jessic ...
- El Ayoubi, Rouwa ...
- Forner, Kathy-An ...
- Roy, Ranjan
- Francois, Moira
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- Griffith, May
- Lillicrap, David
- Yousefi, Azizeh- ...
- Blostein, Mark D
- Galipeau, Jacque ...
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