Lentiviral Gene Therapy for Bone Repair Using Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells

Hum Gene Ther. 2019 Jul;30(7):906-917. doi: 10.1089/hum.2018.054. Epub 2019 Apr 22.


Umbilical cord blood (UCB) has been increasingly explored as an alternative source of stem cells for use in regenerative medicine due to several advantages over other stem-cell sources, including the need for less stringent human leukocyte antigen matching. Combined with an osteoinductive signal, UCB-derived mesenchymal stem cells (MSCs) could revolutionize the treatment of challenging bone defects. This study aimed to develop an ex vivo regional gene-therapy strategy using BMP-2-transduced allogeneic UCB-MSCs to promote bone repair. To this end, human UCB-MSCs were transduced with a lentiviral vector carrying the cDNA for BMP-2 (LV-BMP-2). In vitro assays to determine the UCB-MSC osteogenic potential and BMP-2 production were followed by in vivo implantation of LV-BMP-2-transduced UCB-MSCs in a mouse hind-limb muscle pouch. Non-transduced and LV-GFP-transduced UCB-MSCs were used as controls. Transduction with LV-BMP-2 was associated with abundant BMP-2 production and induction of osteogenic differentiation in vitro. Implantation of BMP-2-transduced UCB-MSCs led to robust heterotopic bone formation 4 weeks postoperatively, as seen on radiographs and histology. These results, along with the fact that UCB-MSCs can be easily collected with no donor-site morbidity and low immunogenicity, suggest that UCB might be a preferable allogeneic source of MSCs to develop an ex vivo gene-therapy approach to treat difficult bone-repair scenarios.

Keywords: gene therapy; BMP-2; bone repair; lentivirus; umbilical cord blood.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Bone Morphogenetic Protein 2 / genetics*
  • Bone Regeneration
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Disease Models, Animal
  • Fetal Blood / cytology*
  • Gene Expression
  • Gene Order
  • Gene Transfer Techniques
  • Genetic Therapy* / methods
  • Genetic Vectors / genetics*
  • Humans
  • Lentivirus / genetics*
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Phenotype
  • Transduction, Genetic
  • Transgenes


  • Biomarkers
  • Bone Morphogenetic Protein 2