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Enhanced Bone Fracture Healing with Engineered Mesenchymal Stem Cells

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Review of “Acceleration of Fracture Healing by Overexpression of Basic Fibroblast Growth Factor in the Mesenchymal Stromal Cells” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Strategies employed to enhance bone fracture healing have met with varying success, but the team of researchers led by Wei Yao (UC Davis, USA) thinks they have hit on a potentially efficient approach. Previous studies highlighted the application of mesenchymal stem cells (MSCs) overexpressing certain growth factors [1-3] to promote bone fracture healing by mediating localized slow-release of pro-regenerative factors. In a new STEM CELLS Translational Medicine study, Zhang et al. have now assessed the effect of MSCs overexpressing basic fibroblast growth factor (bFGF) as a safe and efficient means to effectively enhance bone fracture healing [4].

The study first established that their engineered bFGF-transduced MSCs (bFGF-MSCs) exhibited heightened levels of intracellular and extracellular bFGF, as well as elevated levels of secreted VEGF, an angiogenic factor that acts synergistically with bFGF to stimulate wound healing. Subsequent intramuscular injection of bFGF-MSCs adjacent to closed-femoral fractures in model mice promoted migration and incorporation of bFGF-MSCs into the fracture site.

When compared to the transplantation of unmodified MSC transplantation, the heightened numbers of bFGF-MSCs secreting high levels of paracrine-acting factors enhanced bone fracture healing and increased bone strength by stimulating endogenous angiogenesis, osteogenesis, and rapid cartilage turnover through endochondral ossification.

This exciting new study suggests that engineered bFGF-overexpressing MSCs can potentially reduce the time required for effective fracture healing and recovered bone strength by creating a highly pro-regenerative wound environment comprising stem cells and growth factors that stimulate angiogenesis, osteoblast differentiation, and bone formation. 

Will we see bFGF-MSCs moving into a large-animal model of bone fracture healing and onwards to human trials? Stay tuned to the Stem Cells Portal to find out!

Discussion Points

  • Can bFGF-overexpressing MSCs aid repair/regeneration of other tissues?
  • Are bFGF-overexpressing MSCs safe in the long term?
  • What other factors/factor combinations may prove useful? 

References

  1. Granero-Molto F, Myers TJ, Weis JA, et al. Mesenchymal stem cells expressing insulin-like growth factor-I (MSCIGF) promote fracture healing and restore new bone formation in Irs1 knockout mice: analyses of MSCIGF autocrine and paracrine regenerative effects. Stem Cells 2011;29:1537-1548.
  2. Gamradt SC and Lieberman JR. Genetic modification of stem cells to enhance bone repair. Ann Biomed Eng 2004;32:136-147.
  3. Tai K, Pelled G, Sheyn D, et al. Nanobiomechanics of repair bone regenerated by genetically modified mesenchymal stem cells. Tissue Eng Part A 2008;14:1709-1720.
  4. Zhang H, Kot A, Lay Y-AE, et al. Acceleration of Fracture Healing by Overexpression of Basic Fibroblast Growth Factor in the Mesenchymal Stromal Cells. STEM CELLS Translational Medicine 2017;6:1880-1893.