Abstract
Bone morphogenetic protein-2 (BMP-2) is known to be an active inducer of osteoblast differentiation and mesenchymal stem cells (MSCs) have been applied as an alternative strategy for bone regeneration. The aim of this study was to evaluate the combined effects of easily accessible MSCs easily harvested in the outpatient department under local anesthesia and BMP-2 on the bone regeneration using rabbit calvarial defect model. The defects measuring 6 mm in diameter were prepared in the cavarium of New Zealand white rabbits. The MSCs were isolated from the mandible during the tooth extraction. The defects were grafted with 1) β-tricalcium phosphate/hydroxyapatite (β-TCP/HA) only, 2) 1×106 MSCs loaded with β-TCP/HA, 3) β-TCP/HA containing recombinant human BMP-2, and 4) 1×106 MSCs loaded with β-TCP/HA containing rhBMP-2. Groups without any graft material served as negative control. At 4 weeks, highest bone formation was achieved in β-TCP/HA+rhBMP-2+MSC group and there was statistically significant increase of bone fill in the β-TCP/HA+rhBMP-2+MSC group when compared with the negative control group (p<0.05). The quantity of new bone at 6 weeks was greater than that observed at 4 weeks in each group and alkaline phosphatase staining was evident throughout the images in groups implanted with graft material. This study showed that combining easily accessible MSCs and commercially available BMP-2 resulted in significant increase of bone regeneration. Within the limits of this study, it could suggest that the MSCs from mandible may be combined with BMP-2 to enhance bone regeneration in early healing period.
Similar content being viewed by others
References
Zhang Z. Bone regeneration by stem cell and tissue engineering in oral and maxillofacial region. Front Med 2011;5:401–413.
Miranda SC, Silva GA, Mendes RM, Abreu FA, Caliari MV, Alves JB, et al. Mesenchymal stem cells associated with porous chitosan-gelatin scaffold: a potential strategy for alveolar bone regeneration. J Biomed Mater Res A 2012;100:2775–2786.
Gamie Z, Tran GT, Vyzas G, Korres N, Heliotis M, Mantalaris A, et al. Stem cells combined with bone graft substitutes in skeletal tissue engineering. Expert Opin Biol Ther 2012;12:713–729.
Park JB, Bae SS, Lee PW, Lee W, Park YH, Kim H, et al. Comparison of stem cells derived from periosteum and bone marrow of jaw bone and long bone in rabbit models. Tissue Eng Regen Med 2012;9:224–230.
Park JB, Lee KS, Lee W, Kim HS, Lee KH, Kim IS. Establishment of the chronic bone defect model in experimental model mandible and evaluation of the efficacy of the mesenchymal stem cells in enhancing bone regeneration. Tissue Eng Regen Med 2013;10:18–24.
Fawzy El-Sayed KM, Paris S, Becker ST, Neuschl M, De Buhr W, Sälzer S, et al. Periodontal regeneration employing gingival margin-derived stem/ progenitor cells: an animal study. J Clin Periodontol 2012;39:861–870.
Wang HL, Boyapati L. “PASS” principles for predictable bone regeneration. Implant Dent 2006;15:8–17.
Pieri F, Lucarelli E, Corinaldesi G, Fini M, Aldini NN, Giardino R, et al. Effect of mesenchymal stem cells and platelet-rich plasma on the healing of standardized bone defects in the alveolar ridge: a comparative histomorphometric study in minipigs. J Oral Maxillofac Surg 2009;67:265–272.
Novaes AB Jr, Papalexiou V, Luczyszyn SM, Muglia VA, Souza SL, Taba Júnior M. Immediate implant in extraction socket with acellular dermal matrix graft and bioactive glass: a case report. Implant Dent 2002;11:343–348.
Kuhn LT, Ou G, Charles L, Hurley MM, Rodner CM, Gronowicz G. Fibroblast growth factor-2 and bone morphogenetic protein-2 have a synergistic stimulatory effect on bone formation in cell cultures from elderly mouse and human bone. J Gerontol A Biol Sci Med Sci 2013;68:1170–1180.
Hughes-Fulford M, Li CF. The role of FGF-2 and BMP-2 in regulation of gene induction, cell proliferation and mineralization. J Orthop Surg Res 2011;6:8.
Park JB, Lee JY, Park HN, Seol YJ, Park YJ, Rhee SH, et al. Osteopromo-tion with synthetic oligopeptide-coated bovine bone mineral in vivo. J Periodontol 2007;78:157–163.
DeConde AS, Sidell D, Lee M, Bezouglaia O, Low K, Elashoff D, et al. Bone morphogenetic protein-2-impregnated biomimetic scaffolds successfully induce bone healing in a marginal mandibular defect. Laryngo-scope 2013;123:1149–1155.
Hu W, Ye Y, Wang J, Zhang W, Chen A, Guo F. Bone morphogenetic proteins induce rabbit bone marrow-derived mesenchyme stem cells to differentiate into osteoblasts via BMP signals pathway. Artif Cells Nanomed Biotechnol 2013;41:249–254.
Arinzeh TL, Peter SJ, Archambault MP, van den Bos C, Gordon S, Kraus K, et al. Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. J Bone Joint Surg Am 2003;85-A:1927–1935.
Kraus KH, Kirker-Head C. Mesenchymal stem cells and bone regeneration. Vet Surg 2006;35:232–242.
Park BW. Dental tissues as adult stem cell source. J Korean Assoc Oral Maxillofac Surg 2013;39:41–42.
Kim JY, Kim MR, Kim SJ. Modulation of osteoblastic/odontoblastic dif-ferentiation of adult mesenchymal stem cells through gene introduction: a brief review. J Korean Assoc Oral Maxillofac Surg 2013;39:55–62.
Yun KI, Kim DJ, Park JU. Osteogenic potential of adult stem cells from human maxillary sinus membrane by Simvastatin in vitro: preliminary report. J Korean Assoc Oral Maxillofac Surg 2013;39:150–155.
Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, et al. Im-proved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells 2006;24:2292–2298.
Seo JP, Tanabe T, Tsuzuki N, Haneda S, Yamada K, Furuoka H, et al. Ef-fects of bilayer gelatin/ß-tricalcium phosphate sponges loaded with mesenchymal stem cells, chondrocytes, bone morphogenetic protein-2, and platelet rich plasma on osteochondral defects of the talus in horses. Res Vet Sci 2013;95:1210–1216.
Kim J, Kim IS, Cho TH, Lee KB, Hwang SJ, Tae G, et al. Bone regenera-tion using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells. Biomaterials 2007;28:1830–1837.
Terella A, Mariner P, Brown N, Anseth K, Streubel SO. Repair of a calvar-ial defect with biofactor and stem cell-embedded polyethylene glycol scaf-fold. Arch Facial Plast Surg 2010;12:166–171.
Song YG, Cho IH. Characteristics and osteogenic effect of zirconia po-rous scaffold coated with ß-TCP/HA. J Adv Prosthodont 2014;6:285–294.
Sulaiman SB, Keong TK, Cheng CH, Saim AB, Idrus RB. Tricalcium phosphate/hydroxyapatite (TCP-HA) bone scaffold as potential candidate for the formation of tissue engineered bone. Indian J Med Res 2013; 137:1093–1101.
Hannink G, Geutjes PJ, Daamen WF, Buma P. Evaluation of collagen/ heparin coated TCP/HA granules for long-term delivery of BMP-2. J Mater Sci Mater Med 2013;24:325–332.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Park, JB., Kim, KY., Lee, W. et al. Combinatorial effect of stem cells derived from mandible and recombinant human bone morphogenetic protein-2. Tissue Eng Regen Med 12, 343–351 (2015). https://doi.org/10.1007/s13770-014-0038-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13770-014-0038-3