Acceleration of Fracture Healing by Overexpression of Basic Fibroblast Growth Factor in the Mesenchymal Stromal Cells

Hongliang Zhang, Alexander Kot, Yu An E. Lay, Fernando A Fierro, Haiyan Chen, Nancy E Lane, Wei Yao

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

In this study, we engineered mesenchymal stem cells (MSCs) to over-express basic fibroblast growth factor (bFGF) and evaluated its effects on fracture healing. Adipose-derived mouse MSCs were transduced to express bFGF and green fluorescence protein (ADSCbFGF-GFP). Closed-femoral fractures were performed with osterix-mCherry reporter mice of both sexes. The mice received 3 × 105 ADSCs transfected with control vector or bFGF via intramuscular injection within or around the fracture sites. Mice were euthanized at days 7, 14, and 35 to monitor MSC engraftment, osteogenic differentiation, callus formation, and bone strength. Compared to ADSC culture alone, ADSCbFGF increased bFGF expression and higher levels of bFGF and vascular endothelial growth factor (VEGF) in the culture supernatant for up to 14 days. ADSCbFGF treatment increased GFP-labeled MSCs at the fracture gaps and these cells were incorporated into the newly formed callus. quantitative reverse transcription polymerase chain reaction (qRT-PCR) from the callus revealed a 2- to 12-fold increase in the expression of genes associated with nervous system regeneration, angiogenesis, and matrix formation. Compared to the control, ADSCbFGF treatment increased VEGF expression at the periosteal region of the callus, remodeling of collagen into mineralized callus and bone strength. In summary, MSCbFGF accelerated fracture healing by increasing the production of growth factors that stimulated angiogenesis and differentiation of MSCs to osteoblasts that formed new bone and accelerated fracture repair. This novel treatment may reduce the time required for fracture healing. Stem Cells Translational Medicine 2017;6:1880–1893.

Original languageEnglish (US)
Pages (from-to)1880-1893
Number of pages14
JournalStem cells translational medicine
Volume6
Issue number10
DOIs
StatePublished - Oct 1 2017

Fingerprint

Fracture Healing
Bony Callus
Fibroblast Growth Factor 2
Mesenchymal Stromal Cells
Vascular Endothelial Growth Factor A
Growth Differentiation Factors
Closed Fractures
Femoral Fractures
Translational Medical Research
Intramuscular Injections
Bone Fractures
Osteoblasts
Osteogenesis
Nervous System
Reverse Transcription
Regeneration
Collagen
Stem Cells
Therapeutics
Fluorescence

Keywords

  • Basic fibroblast growth factor
  • Bone strength
  • Callus
  • Mesenchymal stromal cells
  • Osteoblasts

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Acceleration of Fracture Healing by Overexpression of Basic Fibroblast Growth Factor in the Mesenchymal Stromal Cells. / Zhang, Hongliang; Kot, Alexander; Lay, Yu An E.; Fierro, Fernando A; Chen, Haiyan; Lane, Nancy E; Yao, Wei.

In: Stem cells translational medicine, Vol. 6, No. 10, 01.10.2017, p. 1880-1893.

Research output: Contribution to journalArticle

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