Enhancement of ectopic bone formation by bone morphogenetic protein-2 delivery using heparin-conjugated PLGA nanoparticles with transplantation of bone marrow-derived mesenchymal stem cells

Sung Eun Kim, Oju Jeon, Jung Bok Lee, Min Soo Bae, Heoung Jae Chun, Seong Hwan Moon, Il Keun Kwon

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49 Citations (Scopus)

Abstract

This study was performed to determine if a combination of previously undifferentiated bone marrow-derived mesenchymal stem cells (BMMSCs) and exogenous bone morphogenetic protein-2 (BMP-2) delivered via heparin-conjugated PLGA nanoparticles (HCPNs) would extensively regenerate bone in vivo. In vitro testing found that the HCPNs were able to release BMP-2 over a 2-week period. Human BMMSCs cultured in medium containing BMP-2-loaded HCPNs for 2 weeks differentiated toward osteogenic cells expressing alkaline phosphatase (ALP), osteopontin (OPN) and osteocalcin (OCN) mRNA, while cells without BMP-2 expressed only ALP. In vivo testing found that undifferentiated BMMSCs with BMP-2-loaded HCPNs induce far more extensive bone formation than either implantation of BMP-2-loaded HCPNs or osteogenically differentiated BMMSCs. This study demonstrates the feasibility of extensive in vivo bone regeneration by transplantation of undifferentiated BMMSCs and BMP-2 delivery via HCPNs.

Original languageEnglish
Pages (from-to)771-777
Number of pages7
JournalJournal of Biomedical Science
Volume15
Issue number6
DOIs
Publication statusPublished - 2008 Nov

Bibliographical note

Funding Information:
staining of histological sections formed by implantation of (a) undifferentiated BMMSCs suspended in fibrin gel (group 1), (b) osteogenic differentiated BMMSCs suspended in fibrin gel (group 2), (c) BMP-2-loaded HCPNs suspended in fibrin gel (group 3), and (d) BMP-2- loaded HCPNs and undifferentiated BMMSCs suspended in fibrin gel (group 4) into the dorsal subcutaneous spaces of athymic mice for 8 weeks. The scale bar indicates 100 µm and all photographs were taken at the same magnification. (e) Bone formation area and (f) calcium deposition in the implants at 8 weeks after implantation. The differences between all the groups were statistically significant (p \ 0.05) Acknowledgments This work was supported, in part, by grant No. R01-2006-000-10933-0 from the Basic Research Program of the Korea Science & Engineering Foundation and by School of Dentistry, Kyung Hee University.

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

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