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

doi:10.1007/s11373-008-9277-4

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

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	771-777
Number of pages	7
Journal	Journal of Biomedical Science
Volume	15
Issue number	6
DOIs	https://doi.org/10.1007/s11373-008-9277-4
Publication status	Published - 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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10.1007/s11373-008-9277-4

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Kim, S. E., Jeon, O., Lee, J. B., Bae, M. S., Chun, H. J., Moon, S. H., & Kwon, I. K. (2008). 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. Journal of Biomedical Science, 15(6), 771-777. https://doi.org/10.1007/s11373-008-9277-4

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title = "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",

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.",

author = "Kim, {Sung Eun} and Oju Jeon and Lee, {Jung Bok} and Bae, {Min Soo} and Chun, {Heoung Jae} and Moon, {Seong Hwan} and Kwon, {Il Keun}",

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.",

year = "2008",

month = nov,

doi = "10.1007/s11373-008-9277-4",

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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. / Kim, Sung Eun; Jeon, Oju; Lee, Jung Bok et al.
In: Journal of Biomedical Science, Vol. 15, No. 6, 11.2008, p. 771-777.

Research output: Contribution to journal › Article › peer-review

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AU - Kim, Sung Eun

AU - Jeon, Oju

AU - Lee, Jung Bok

AU - Bae, Min Soo

AU - Chun, Heoung Jae

AU - Moon, Seong Hwan

AU - Kwon, Il Keun

N1 - 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.

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N2 - 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.

AB - 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.

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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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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