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

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.

Cuerquis, JessicaMcGill University, Montreal, Canada (författare)
El Ayoubi, RouwaydaNatl Res Council Canada, Boucherville, Canada (författare)
Forner, Kathy-AnnMcGill University, Montreal, Canada (författare)
Roy, RanjanMcGill University, Montreal, Canada (författare)
Francois, MoiraMcGill University, Montreal, Canada (författare)
Griffith, MayOttawa Health Research Institute, Ottawa, Canada(Swepub:liu)maygr76 (författare)
Lillicrap, DavidQueen’s University, Kingston, Canada (författare)
Yousefi, Azizeh-MitraNatl Res Council Canada, Boucherville, Canada (författare)
Blostein, Mark DMcGill University, Montreal, Canada (författare)
Galipeau, JacquesMcGill University, Montreal, Canada (författare)
McGill University, Montreal, CanadaNatl Res Council Canada, Boucherville, Canada (creator_code:org_t)

Av författaren/redakt...: Coutu, Daniel L; Cuerquis, Jessic ...; El Ayoubi, Rouwa ...; Forner, Kathy-An ...; Roy, Ranjan; Francois, Moira; visa fler...; Griffith, May; Lillicrap, David; Yousefi, Azizeh- ...; Blostein, Mark D; Galipeau, Jacque ...; visa färre...

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