Enhanced critical-size calvarial bone healing by ASCs engineered with Cre/loxP-based hybrid baculovirus

Shih Chun Lo, Kuei Chang Li, Yu Han Chang, Mu Nung Hsu, Li Yu Sung, Truong Anh Vu, Yu Chen Hu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

43 Scopus citations

Abstract

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 ≈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 Cre/loxP-based hybrid baculovirus vector for ASCs engineering and calvarial bone healing.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalBiomaterials
Volume124
DOIs
StatePublished - 01 04 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Elsevier Ltd

Keywords

  • Adipose-derived stem cells
  • BMP-2
  • Baculovirus
  • Calvarial bone healing
  • Cre/loxP
  • SDF-1

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