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

作者：Coutu Daniel L; Cuerquis Jessica; El Ayoubi Rouwayda; Forner Kathy Ann; Roy Ranjan; Francois Moira; Griffith May; Lillicrap David; Yousefi Azizeh Mitra; Blostein Mark D; Galipeau Jacques^*

来源：Biomaterials, 2011, 32(1): 295-305.

DOI：10.1016/j.biomaterials.2010.08.094

• Mesenchymal stem cells
• Gene therapy
• Hemophilia
• Biomineralization
• Self-renewal
• Osteogenesis

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.

• 出版日期2011-1
• 单位河北医科大学