The effect of erythropoietin on autologous stem cell-mediated bone regeneration

Biomaterials. 2013 Oct;34(30):7364-71. doi: 10.1016/j.biomaterials.2013.06.031. Epub 2013 Jul 4.

Abstract

Mesenchymal stem cells (MSCs) although used for bone tissue engineering are limited by the requirement of isolation and culture prior to transplantation. Our recent studies have shown that biomaterial implants can be engineered to facilitate the recruitment of MSCs. In this study, we explore the ability of these implants to direct the recruitment and the differentiation of MSCs in the setting of a bone defect. We initially determined that both stromal derived factor-1alpha (SDF-1α) and erythropoietin (Epo) prompted different degrees of MSC recruitment. Additionally, we found that Epo and bone morphogenetic protein-2 (BMP-2), but not SDF-1α, triggered the osteogenic differentiation of MSCs in vitro. We then investigated the possibility of directing autologous MSC-mediated bone regeneration using a murine calvaria model. Consistent with our in vitro observations, Epo-releasing scaffolds were found to be more potent in bridging the defect than BMP-2 loaded scaffolds, as determined by computed tomography (CT) scanning, fluorescent imaging and histological analyses. These results demonstrate the tremendous potential, directing the recruitment and differentiation of autologous MSCs has in the field of tissue regeneration.

Keywords: Autologous stem cells; Bone morphogenetic protein-2; Bone tissue engineering; Erythropoietin; Scaffold; Stromal derived factor-1α.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Regeneration / drug effects*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Chemokines / pharmacology
  • Chemotaxis / drug effects
  • Erythropoietin / pharmacology*
  • Immunohistochemistry
  • Implants, Experimental
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Osteogenesis / drug effects
  • Skull / diagnostic imaging
  • Skull / drug effects
  • Skull / pathology
  • Tissue Scaffolds / chemistry
  • Transplantation, Autologous
  • X-Ray Microtomography

Substances

  • Chemokines
  • Erythropoietin