Journal
BIOMATERIALS
Volume 124, Issue -, Pages 1-11Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.01.033
Keywords
Adipose-derived stem cells; Baculovirus; BMP-2; Calvarial bone healing; Cre/loxP; SDF-1
Funding
- National Tsing Hua University (Toward World-Class University) [104N2050E1, 105N526CE1]
- CGMH Intramural Project [CRRPG3E0172, CMRPG3E0441, CMRPG3E0061, CMRPG3B1542, CMRPG3B1541]
- Ministry of Science and Technology, Taiwan [MOST 104-2221-E-007-088-MY3, 103-2221-E-007-093-MY3, 101-2628-E-007-009-MY3]
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Calvarial bone repair remains challenging for adults. Although adipose-derived stem cells (ASCs) hold promise to heal bone defects, use of ASCs for critical-size calvarial bone repair is ineffective. Stromal cell derived factor 1 (SDF-1) is a chemokine capable of triggering stem cell migration. Although recombinant SDF-1 protein is co-delivered with other molecules including BMP-2 to facilitate calvarial bone repair, these approaches did not yield satisfactory healing. This study aimed to exploit a newly developed Cre/loxP-based hybrid baculovirus for efficient gene delivery and prolonged transgene expression in ASCs. We demonstrated that transduction of rat ASCs with the hybrid Cre/loxP-based baculovirus enabled robust and sustained expression of functional BMP-2 and SDF-1. Expression of BMP-2 or SDF-1 alone failed to effectively induce rat ASCs osteogenesis and healing of critical-size calvarial bone defects. Nonetheless, prolonged BMP-2/SDF-1 co-expression in ASCs synergistically activated both Smad and ERK1/2 pathways and hence potentiated the osteogenesis. Consequently, transplantation of the hybrid baculovirus-engineered, BMP-2/SDF-1-expressing ASCs/scaffold constructs potently healed the critical size (6 mm) calvarial bone defects (filling approximate to 70% of defect volume), which considerably outperformed the calvarial bone repair using BMP-2/SDF-1 delivered with biomaterial-based scaffolds. These data implicated the potential of CrefioxP-based hybrid baculovirus vector for ASCs engineering and calvarial bone healing. (C) 2017 Elsevier Ltd. All rights reserved.
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