Osteogenic graft vascularization and bone resorption by VEGF-expressing human mesenchymal progenitors

Helmrich U., Di Maggio N., Gueven S., Groppa E., Melly L., Largo R. D., ...Daha Fazla

BIOMATERIALS, cilt.34, sa.21, ss.5025-5035, 2013 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 34 Sayı: 21
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1016/j.biomaterials.2013.03.040
  • Dergi Adı: BIOMATERIALS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.5025-5035
  • Anahtar Kelimeler: Angiogenesis, Bone tissue engineering, Mesenchymal stem cell, Osteoclast, Silicate-substituted apatite, VEGF
  • Dokuz Eylül Üniversitesi Adresli: Hayır

Özet

Rapid vascularisation of tissue-engineered osteogenic grafts is a major obstacle in the development of regenerative medicine approaches for bone repair. Vascular endothelial growth factor (VEGF) is the master regulator of vascular growth. We investigated a cell-based gene therapy approach to generate osteogenic grafts with an increased vascularization potential in an ectopic nude rat model in vivo, by genetically modifying human bone marrow-derived stromal/stem cells (BMSC) to express rat VEGF. BMSC were loaded onto silicate-substituted apatite granules, which are a clinically established osteoconductive material. Eight weeks after implantation, the vascular density of constructs seeded with VEGF-BMSC was 3-fold greater than with control cells, consisting of physiologically structured vascular networks with both conductance vessels and capillaries. However, VEGF specifically caused a global reduction in bone quantity, which consisted of thin trabeculae of immature matrix. VEGF did not impair BMSC engraftment in vivo, but strongly increased the recruitment of TRAP- and Cathepsin K-positive osteoclasts. These data suggest that VEGF over-expression is effective to improve the vascularization of osteogenic grafts, but also has the potential to disrupt bone homoeostasis towards excessive degradation, posing a challenge to its clinical application in bone tissue engineering. (C) 2013 Elsevier Ltd. All rights reserved.