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.
Bibliographical noteFunding 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)