Abstract
We have hypothesized that human bone marrow-derived mesenchymal stem cells (BMMSCs), that are not osteogenically differentiated prior to implantation, would regenerate bone extensively in vivo once exogenous bone morphogenetic protein-2 (BMP-2) was delivered to the implantation site. BMP-2 released from heparin-conjugated poly(lactic-co-glycolic acid) (HCPLGA) scaffolds stimulates osteogenic differentiation of cultured BMMSCs. Upon implantation, undifferentiated BMMSCs on BMP-2-loaded HCPLGA scaffolds induce far more extensive bone formation than either undifferentiated BMMSCs or osteogenically differentiated BMMSCs on HCPLGA scaffolds. These BMP-2-loaded HCPLGA scaffolds could prove invaluable for in vivo regeneration of bone from undifferentiated human BMMSCs.
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References
Cheng SL, Yang JW, Rifas L et al (1994) Differentiation of human bone marrow osteogenic stromal cells in vitro: induction of the osteoblast phenotype by dexamethasone. Endocrinology 134:277–286
Flautre B, Anselme K, Delecourt C et al (1999) Histological aspects in bone regeneration of an association with porous hydroxyapatite and bone marrow cells. J Mater Sci Mater Med 10:811–814
Fromigue O, Marie PJ, Lomri A (1998) Bone morphogenetic protein-2 and transforming growth factor-beta2 interact to modulate human bone marrow stromal cell proliferation and differentiation. J Cell Biochem 68:411–426
Haynesworth SE, Goshima J, Goldberg VM et al (1992) Characterization of cells with osteogenic potential from human marrow. Bone 13:81–88
Huang W, Carlsen B, Wulur I et al (2004) BMP-2 exerts differential effects on differentiation of rabbit bone marrow stromal cells grown in two-dimensional and three-dimensional systems and is required for in vitro bone formation in a PLGA scaffold. Exp Cell Res 299:325–334
Ito C, Evans WE, McNinch L et al (1996) Comparative cytotoxicity of dexamethasone and prednisolone in childhood acute lymphoblastic leukemia. J Clin Oncol 14:2370–2376
Jaiswal N, Haynesworth SE, Caplan AI et al (1997) Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem 64:295–312
Jeon O, Song SJ, Kang SW et al (2007) Enhancement of ectopic bone formation by bone morphogenetic protein-2 released from heparin-conjugated poly(L-lactic-co-glycolic acid) scaffold. Biomaterials 28:2763–2771
Malaval L, Modrowski D, Gupta AK et al (1994) Cellular expression of bone-related proteins during in vitro osteogenesis in rat bone marrow stromal cell cultures. J Cell Physiol 158:555–572
Niemeyer P, Krause U, Fellenberg J et al (2004) Evaluation of mineralized collagen and alpha-tricalcium phosphate as scaffolds for tissue engineering of bone using human mesenchymal stem cells. Cells Tissues Organs 177:68–78
Owen TA, Aronow M, Shalhoub V et al (1990) Progressive development of the rat osteoblast phenotype in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix. J Cell Physiol 143:420–430
Park MS, Kim SS, Cho SW et al (2006) Enhancement of the osteogenic efficacy of osteoblast transplantation by the sustained delivery of basic fibroblast growth factor. J Biomed Mater Res B 79:353–359
Petite H, Viateau V, Bensaid W et al (2000) Tissue-engineered bone regeneration. Nat Biotechnol 18:959–963
Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147
Quarto R, Mastrogiacomo M, Cancedda R et al (2001) Repair of large bone defects with the use of autologous bone marrow stromal cells. N Engl J Med 344:385–386
Song SJ, Jeon O, Yang HS et al (2007) The effects of culture conditions on osteogenic differentiation in human mesenchymal stem cells. J Microbiol Biotechnol 17:1113–1119
Sun JS, Chang WHS, Chen LT et al (2004) The influence on gene-expression profiling of osteoblasts behavior following treatment with the ionic products of sintered b-dicalcium pyrophosphate dissolution. Biomaterials 25:607–616
van den Dolder J, Farber E, Spauwen PH et al (2003) Bone tissue reconstruction using titanium fiber mesh combined with rat bone marrow stromal cells. Biomaterials 24:1745–1750
Yamamoto M, Takahashi Y, Tabata Y (2003) Controlled release by biodegradable hydrogels enhances the ectopic bone formation of bone morphogenetic protein. Biomaterials 24:4375–4383
Yoshikawa T, Ohgushi H, Akahane M et al (1998) Analysis of gene expression in osteogenic cultured marrow/hydroxyapatite construct implanted at ectopic sites: a comparison with the osteogenic ability of cancellous bone. J Biomed Mater Res 41:568–573
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This work was supported by a grant (SC 3220) from the Stem Cell Research Center of the 21st Century Frontier Program, which is funded by the Ministry of Science and Technology, Republic of Korea.
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Sun-Woong Kang and Wan-Geun La have contributed equally to this work.
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Kang, SW., La, WG., Kang, J.M. et al. Bone morphogenetic protein-2 enhances bone regeneration mediated by transplantation of osteogenically undifferentiated bone marrow-derived mesenchymal stem cells. Biotechnol Lett 30, 1163–1168 (2008). https://doi.org/10.1007/s10529-008-9675-8
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DOI: https://doi.org/10.1007/s10529-008-9675-8