Prolonged osteogenesis from human mesenchymal stem cells implanted in immunodeficient mice by using coralline hydroxyapatite incorporating rhBMP2 microspheres

Kun Fu, Qingguo Xu, Jan Czernuszka, Charles E. McKenna, Frank H. Ebetino, R. Graham G. Russell, James T. Triffitt, Zhidao Xia

Research output: Contribution to journalArticlepeer-review

Abstract

The local environment plays an important role in osteogenic tissue regeneration. Our previous studies have shown that xenogenic transplantation of human mesenchymal stem cells (hMSCs) alone into immunodeficient mice did not result in long-term bone formation. This study investigates whether bone formation can be prolonged by incorporating human mesenchymal stem cells in mineralized scaffolds together with controlled delivery of a growth factor, BMP2. A composite of coralline hydroxyapatite (CHA) with poly(lactic-co-glycolic acid) (PLGA)-encapsulated rhBMP2 was incorporated with hMSCs in vitro. After 2 weeks in vitro culture the constructs were implanted subcutaneously in CB17 scid beige mice and harvested 10 weeks after implantation. The mineralized tissues were stained by using a fluorescent marker, 5FAM-risedronate, followed by observation with fluorescence microscopy, histology, histomorphometry, mouse-anti-human vimentin immunohistochemistry, and scanning microscopy. The results showed that compared with control materials in which only fibrous tissue formed following implantation of coralline scaffolds, bone-like tissue formed within the CHA composite containing PLGA encapsulated rhBMP2 and hMSCs for up to 10 weeks after implantation. Human cells, identified by the human vimentin-specific monoclonal antibody were seen within the bone-like tissue. In conclusion, incorporation of hMSCs into CHA with controlled delivery of BMP showed prolonged bone formation in immunodeficient mice. Further research is required to optimize the growth factor delivery system and to understand the underlying cellular and molecular mechanisms involved.

Original languageEnglish (US)
Pages (from-to)1256-1264
Number of pages9
JournalJournal of Biomedical Materials Research - Part A
Volume92
Issue number4
DOIs
StatePublished - Mar 15 2010

Keywords

  • (PLGA)
  • Coralline hydroxyapatite (CHA)
  • Human mesenchymal stem cells (hMSCs)
  • Immunodeficient mice
  • Poly(lactic-co-glycolic acid)
  • Recombinant human bone morphogenetic protein 2 (rhBMP2)

ASJC Scopus subject areas

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

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