Adipose-derived stem cells (ADSCs) have been subject of several studies due to their abundance, ease of preparation, and application in bone regeneration. We aim to compare effectiveness of alveolar reconstruction utilizing human cancellous freeze-dried graft (HCG) and beta tricalcium phosphate (BTP), both seeded with human ADSC (hADSC) and autologous bone graft (ABG).
Material and Methods
A 5 × 5 mm alveolar defect in 36 male Wistar rats were treated using: ABG (C), HCG–hADSC (H1), and BTP–hADSC (H2). At 1 and 8 weeks after surgery, runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osterix (OSX), and bone morphogenetic protein 2 (BMP2; g/mL) were quantified using immunohistochemistry, while bone tissue volume (BV, mm3), bone tissue volume fraction (BF, percentage), and trabecular thickness of bone (TT, mm) were assessed using micro-computed tomography (CT).
Results
One week after surgery, H2 was higher in RUNX2, OSX, ALP, and BMP2 than C (P < .05). Only RUNX2 and OSX were found to be higher in H1 than C, while ALP and BMP2 were higher in H2 than H1. Micro-CT revealed that H2 had a higher TT than C and C had a higher TT than H1 (P < .05). Eight weeks after surgery, both H2 and H1 was higher in RUNX2, OSX, ALP, and BMP2 than C (P < .05). RUNX2 and BMP2 were found to be higher in H1 than H2. Micro-CT revealed that H2 had higher BV and TT than C and H1 (P < .05).
Conclusions
Exogenous hADSC strengthened the effectiveness of HCG and BTP to accelerate osteogenesis, osteoconduction, and osteoinduction. The latter was the most successful in bone formation, followed by HCG and ABG.
Bath-BaloghMFehrenbachM. Periodontium: cementum, alveolar bone and periodontal ligament. In: Illustrated Dental Embryology, Histology, and Anatomy 3rd edition. Elsevier Health Sciences; 2014:179.
2.
AghalooTFelsenfeldA. Principles of repair and grafting of bone and cartilage. In: Current Therapy in Oral and Maxillofacial Surgery. Elsevier; 2011:19-26.
3.
DimitriouRJonesEMcGonagleDGiannoudisPV. Bone regeneration: current concepts and future directions. BMC Med. 2011;9:66. doi:https://doi.org/10.1186/1741-7015-9-66
4.
RawashdehMATelfahH. Secondary alveolar bone grafting: the dilemma of donor site selection and morbidity. Br J Oral Maxillofac Surg. 2008;46(8):665-670. doi:https://doi.org/10.1016/j.bjoms.2008.07.184
5.
BaqainZHAnabtawiMKarakyAAMalkawiZ. Morbidity from anterior iliac crest bone harvesting for secondary alveolar bone grafting: an outcome assessment study. J Oral Maxillofac Surg. 2009;67(3):570-575. doi:https://doi.org/10.1016/j.joms.2008.09.023
6.
GoudySLottDBurtonRWheelerJCanadyJ. Secondary alveolar bone grafting: outcomes, revisions, and new applications. Cleft Palate Craniofac J. 2009;46(6):610-612. doi:https://doi.org/10.1597/08-126.1
HabibovicPde GrootK. Osteoinductive biomaterials—properties and relevance in bone repair. J Tissue Eng Regen Med. 2007;1(1):25-32. doi:https://doi.org/10.1002/term.5
SzpalskiMGunzburgR. Applications of calcium phosphate-based cancellous bone void fillers in trauma surgery. Orthopedics. 2002;25(5 Suppl):s601-s609. http://www.ncbi.nlm.nih.gov/pubmed/12038849
11.
BettachRGuillaumeBTaschieriSDel FabbroM. Clinical performance of a highly porous beta-TCP as the grafting material for maxillary sinus augmentation. Implant Dent. 2014;23(3):357-364. doi:https://doi.org/10.1097/ID.0000000000000102
12.
JiangSDJiangLSDaiLY. Surgical treatment of calcaneal fractures with use of beta-tricalcium phosphate ceramic grafting. Foot Ankle Int. 2008;29(10):1015-1019. doi:https://doi.org/10.3113/FAI.2008.1015
13.
SzpalskiCWetterauMBarrJWarrenSM. Bone tissue engineering: current strategies and techniques—part I: Scaffolds. Tissue Eng Part B Rev. 2012;18(4):246-257. doi:https://doi.org/10.1089/ten.TEB.2011.0427
14.
LiHDaiKTangTZhangXYanMLouJ. Bone regeneration by implantation of adipose-derived stromal cells expressing BMP-2. Biochem Biophys Res Commun. 2007;356(4):836-842. doi:https://doi.org/10.1016/j.bbrc.2007.02.165
15.
YoonEDharSChunDEGharibjanianNAEvansGRD. In vivo osteogenic potential of human adipose-derived stem cells/poly lactide-co-glycolic acid constructs for bone regeneration in a rat critical-sized calvarial defect model. Tissue Eng. 2007;13(3):619-627. doi:https://doi.org/10.1089/ten.2006.0102
Di BellaCFarliePPeningtonAJ. Bone regeneration in a rabbit critical-sized skull defect using autologous adipose-derived cells. Tissue Eng Part A. 2008;14(4):483-490. doi:https://doi.org/10.1089/tea.2007.0137
18.
RadaTReisRLGomesME. Adipose tissue-derived stem cells and their application in bone and cartilage tissue engineering. Tissue Eng Part B Rev. 2009;15(2):113-125. doi:https://doi.org/10.1089/ten.teb.2008.0423
19.
TappHHanleyENPattJCGruberHE. Adipose-derived stem cells: characterization and current application in orthopaedic tissue repair. Exp Biol Med (Maywood). 2009;234(1):1-9. doi:https://doi.org/10.3181/0805/MR-170
20.
Costa AdMBuenoDFMartinsMT, et al.Reconstruction of large cranial defects in nonimmunosuppressed experimental design with human dental pulp stem cells. J Craniofac Surg. 2008;19(1):204-210. doi:https://doi.org/10.1097/scs.0b013e31815c8a54
21.
BuenoDFKerkisICostaAM, et al.New source of muscle-derived stem cells with potential for alveolar bone reconstruction in cleft lip and/or palate patients. Tissue Eng Part A. 2009;15(2):427-435. doi:https://doi.org/10.1089/ten.tea.2007.0417
22.
ChuangCkLinKJLinCY, et al.Xenotransplantation of human mesenchymal stem cells into immunocompetent rats for calvarial bone repair. Tissue Eng Part A. 2010;16(2):479-488. doi:https://doi.org/10.1089/ten.TEA.2009.0401
23.
JazedjeTBuenoDFAlmadaBVP, et al.Human fallopian tube mesenchymal stromal cells enhance bone regeneration in a xenotransplanted model. Stem Cell Rev. 2012;8(2):355-362. doi:https://doi.org/10.1007/s12015-011-9297-8
24.
Raposo-AmaralCEBuenoDFAlmeidaAB, et al.Is bone transplantation the gold standard for repair of alveolar bone defects?J Tissue Eng. 2014;5:2041731413519352. doi:https://doi.org/10.1177/2041731413519352
25.
BanyardDASalibianAAWidgerowADEvansGRD. Implications for human adipose-derived stem cells in plastic surgery. J Cell Mol Med. 2015;19(1):21-30. doi:https://doi.org/10.1111/jcmm.12425
26.
JeonYJKimJChoJHChungHMChaeJI. Comparative analysis of human mesenchymal stem cells derived from bone marrow, placenta, and adipose tissue as sources of cell therapy. J Cell Biochem. 2016;117(5):1112-1125. doi:https://doi.org/10.1002/jcb.25395
27.
RachmanARantamFABachtiarI, et al.Biocompatibility of Yttria-tetragonal zirconia polycrystal seeded with human adipose derived mesenchymal stem cell. Acta Inf Med. 2018;26(4):249-253. doi:https://doi.org/10.5455/aim.2018.26.249-253
NishimuraRHataKMatsubaraTWakabayashiMYonedaT. Regulation of bone and cartilage development by network between BMP signalling and transcription factors. J Biochem. 2012;151(3):247-254. doi:https://doi.org/10.1093/jb/mvs004
30.
PhimphilaiMZhaoZBoulesHRocaHFranceschiRT. BMP Signaling is required for RUNX2-dependent induction of the osteoblast phenotype. J Bone Miner Res. 2006;21(4):637-646. doi:https://doi.org/10.1359/jbmr.060109
31.
ChenDHarrisMARossiniG, et al.Bone morphogenetic protein 2 (BMP-2) enhances BMP-3, BMP-4, and bone cell differentiation marker gene expression during the induction of mineralized bone matrix formation in cultures of fetal rat calvarial osteoblasts. Calcif Tissue Int.1997;60(3):283-290. http://www.ncbi.nlm.nih.gov/pubmed/9069167
32.
KomoriTYagiHNomuraS, et al.Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997;89(5):755-764. http://www.ncbi.nlm.nih.gov/pubmed/9182763
33.
JavedABarnesGLJasanyaBO, et al.Runt homology domain transcription factors (Runx, Cbfa, and AML) mediate repression of the bone sialoprotein promoter: evidence for promoter context-dependent activity of Cbfa proteins. Mol Cell Biol. 2001;21(8):2891-2905. doi:https://doi.org/10.1128/MCB.21.8.2891-2905.2001
34.
MatsubaraTKidaKYamaguchiA, et al.BMP2 regulates osterix through Msx2 and Runx2 during osteoblast differentiation. J Biol Chem. 2008;283(43):29119-29125. doi:https://doi.org/10.1074/jbc.M801774200
35.
KimYJLeeMHWozneyJMChoJYRyooHM. Bone morphogenetic protein-2-induced alkaline phosphatase expression is stimulated by Dlx5 and repressed by Msx2. J Biol Chem. 2004;279(49):50773-50780. doi:https://doi.org/10.1074/jbc.M404145200
36.
YuTPanHHuYTaoHWangKZhangC. Autologous platelet-rich plasma induces bone formation of tissue-engineered bone with bone marrow mesenchymal stem cells on beta-tricalcium phosphate ceramics. J Orthop Surg Res. 2017;12(1):178. doi:https://doi.org/10.1186/s13018-017-0665-1
37.
SaskiantiTNugrahaAPPrahasantiCErnawatiDSSuarditaKRiawanW. Immunohistochemical analysis of stem cells from human exfoliated deciduous teeth seeded in carbonate apatite scaffold for the alveolar bone defect in Wistar rats (Rattus novergicus). F1000Res.2020;9:1164. doi:https://doi.org/10.12688/f1000research.25009.2
38.
BrudererMRichardsRGAliniMStoddartMJ. Role and regulation of RUNX2 in osteogenesis. Eur Cell Mater. 2014;28:269-286. doi:https://doi.org/10.22203/eCM.v028a19
39.
SeebachCHenrichDKählingC, et al.Endothelial progenitor cells and mesenchymal stem cells seeded onto beta-TCP granules enhance early vascularization and bone healing in a critical-sized bone defect in rats. Tissue Eng Part A. 2010;16(6):1961-1970. doi:https://doi.org/10.1089/ten.TEA.2009.0715
40.
ZhouJLinHFangT, et al.The repair of large segmental bone defects in the rabbit with vascularized tissue engineered bone. Biomaterials. 2010;31(6):1171-1179. doi:https://doi.org/10.1016/j.biomaterials.2009.10.043
41.
ParkBZhouLJangK, et al.Enhancement of tibial regeneration in a rat model by adipose-derived stromal cells in a PLGA scaffold. Bone. 2012;51(3):313-323. doi:https://doi.org/10.1016/j.bone.2012.05.019
42.
JahanbinARashedRAlamdariDH, et al.Success of maxillary alveolar defect repair in rats using osteoblast-differentiated human deciduous dental pulp stem cells. J Oral Maxillofac Surg. 2016;74(4):829. doi:https://doi.org/10.1016/j.joms.2015.11.033.
43.
OrbayHBusseBLeachJKSaharDE. The effects of adipose-derived stem cells differentiated into endothelial cells and osteoblasts on healing of critical size calvarial defects. J Craniofac Surg. 2017;28(7):1874-1879. doi:https://doi.org/10.1097/SCS.0000000000003910
44.
SolimanHIsmailHShoumanOBahaaeldinAEl-HadidyMR. Stem cells assisted cancellous bone graft versus stem cells with demineralized bone matrix for alveolar cleft reconstruction. Egypt J Plast Reconstr Surg. 2018;42(1):93-101. http://esprs.org/Content/Journals/Surr.13.pdf
45.
ShahnaseriSSheikhiMHashemibeniBMousaviSSoltaniP. Comparison of autogenous bone graft and tissue-engineered bone graft in alveolar cleft defects in canine animal models using digital radiography. Indian J Dent Res. 2020;31(1):118-123. doi:https://doi.org/10.4103/ijdr.IJDR_156_18
46.
AnghelescuVMNeculaeIDincăO, et al.Inflammatory-driven angiogenesis in bone augmentation with bovine hydroxyapatite, B-tricalcium phosphate, and bioglasses: a comparative study. J Immunol Res. 2018;2018:9349207. doi:https://doi.org/10.1155/2018/9349207
ZhangZZhengYZuJ, et al.Stromal cell-derived factor (SDF)-1α and platelet-rich plasma enhance bone regeneration and angiogenesis simultaneously in situ in rabbit calvaria. J Mater Sci Mater Med. 2021;32(9):125. doi:https://doi.org/10.1007/s10856-021-06600-z
49.
van HoutWMMTMink van der MolenABBreugemCCKooleRVan CannEM. Reconstruction of the alveolar cleft: can growth factor-aided tissue engineering replace autologous bone grafting? A literature review and systematic review of results obtained with bone morphogenetic protein-2. Clin Oral Investig.2011;15(3):297-303. doi:https://doi.org/10.1007/s00784-011-0547-6
50.
HassRKasperCBöhmSJacobsR. Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal. 2011;9(1):12. doi:https://doi.org/10.1186/1478-811X-9-12
51.
LeeMHKwonTGParkHSWozneyJMRyooHM. BMP-2-induced osterix expression is mediated by Dlx5 but is independent of Runx2. Biochem Biophys Res Commun. 2003;309(3):689-694. http://www.ncbi.nlm.nih.gov/pubmed/12963046
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
