Abstract
Successful bone repair is of immense clinical importance. Bone fractures are among the most common injuries encountered and inappropriate healing, estimated to 5–10 %, is expected to further increase along with the increase of the aging population. Cell-based therapies provide an alternative to bone grafting by preventing bone loss and reducing grafting morbidity. Apart from the bone marrow mesenchymal stem cells, a multitude of mesenchymal stem cells from different tissues exhibit osteogenic potential. Among them, mesenchymal stem cells of dental origin, initially isolated but not restricted to the dental pulp, seem to hold a prominent position in the field of bone regeneration. This chapter aims to present the different types of dental stem cells with emphasis on their osteogenic properties and in vivo applications in animal models of bone repair.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Deschaseaux F, Sensébé L, Heymann D (2009) Mechanisms of bone repair and regeneration. Trends Mol Med 15(9):417–429
Schmidt-Bleek K, Schell H, Schulz N, Hoff P, Perka C, Buttgereit F, Volk HD, Lienau J, Duda GN (2012) Inflammatory phase of bone healing initiates the regenerative healing cascade. Cell Tissue Res 347:567–573
Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3(4):393–403
Friedenstein AJ, Piatetzky S II, Petrokova KV (1966) Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 16(3):381–390
Rosset P, Deschaseaux F, Layrolle P (2014) Cell therapy for bone repair. Orthop Traumatol Surg Res 100:S107–S112
Watson L, Elliman SJ, Coleman CM (2014) From isolation to implantation: a concise review of mesenchymal stem cell therapy in bone fracture repair. Stem Cell Res Ther 5(2):51
Gronthos S, Mankani M, Brahim J, Gehron Rodoy P, Shi S (2000) Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A 97:13625–13630
Liu J, Yu F, Sun Y, Jiang B, Zhang W, Yang J, Xu GT, Liang A, Liu S (2015) Concise reviews: characteristics and potential applications of human dental tissue-derived mesenchymal stem cells. Stem Cells 33:627–638
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop DJ, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317
Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, DenBesten P, Gehron Rodoy P, Shi S (2002) Stem cell properties of human dental pulp cells. J Dent Res 81:531–535
Kawashima N (2012) Characterisation of dental pulp stem cells: A new horizon for tissue regeneration? Arch Oral Biol 57:1439–1458
Alge DL, Zhou D, Adams LL, Wyss BK, Shadday MD, Woods EJ, Gabriel Chu TM, Goebel WS (2010) Donor-matched comparison of dental pulp stem cells and bone marrow-derived mesenchymal stem cells in a rat model. J Tissue Eng Regen Med 4(1):73–81
Peng L, Ye L, Zhou XD (2009) Mesenchymal stem cells and tooth engineering. Int J Oral Sci 1:6–12
Armiñán A, Gandía C, Bartual M, García-Verdugo JM, Lledó E, Mirabet V, Llop M, Barea J, Montero JA, Sepúlveda P (2009) Cardiac differentiation is driven by NKX2.5 and GATA4 nuclear translocation in tissue-specific mesenchymal stem cells. Stem Cells Dev 18:907–918
Arthur A, Rychkov G, Shi S, Koblar SA, Gronthos S (2008) Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues. Stem Cells 26:1787–1795
d’Aquino R, Graziano A, Sampaolesi M, Laino G, Pirozzi G, de Rosa A, Papaccio G (2007) Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation. Cell Death Differ 14:1162–1171
Iohara K, Zheng L, Ito M, Tomokiyo A, Matsushita K, Nakashima M (2006) Side populations isolated from porcine dental pulp tissue with self-renewal and multipotency for dentinogenesis, chondrogenesis, adipogenesis and neurogenesis. Stem Cells 24:2493–2503
Király M, Kádár K, Horváthy DB, Nardai P, Rácz GZ, Lacza Z, Varga G, Gerber G (2011) Integration of neuronally predifferentiated human dental pulp stem cells into rat brain in vivo. Neurochem Int 59(3):371–381
Laino G, d’Aquino R, Graziano A, Lanza V, Carinci F, Naro F, Pirozzi G, Papaccio G (2005) Α new population of human adult dental pulp stem cells: a useful source of living autologous fibrous bone tissue (LAB). J Bone Miner Res 20:1394–1402
Patil R, Kumar BM, Lee WJ, Jeon RH, Jang SJ, Lee YM, Park BW, Byun JH, Ahn CS, Kim JW, Rho GJ (2014) Multilineage potential and proteomic profiling of human dental stem cells derived from a single donor. Exp Cell Res 320:92–107
Stevens A, Zuliani T, Olejnik C, LeRoy H, Obriot H, Kerr-Conte J, Formstecher P, Bailliez Y, Polakowska RR (2008) Human dental pulp cells differentiate into neural crest-derived melanocytes and have label-retaining and sphere-forming abilities. Stem Cells Dev 17:1175–1184
Zhang W, Walboomers XF, van Kuppevelt TH, Daamen WF, Bian Z, Jansen JA (2006) The performance of human dental pulp stem cells on different three-dimensional scaffold materials. Biomaterials 27:5658–5668
About I, Bottero MJ, de Denato P, Camps J, Franquin JC, Mitsiadis TA (2000) Human dentin production in vitro. Exp Cell Res 258(1):33–41
About I, Laurent-Maquin D, Lendahl U, Mitsiadis TA (2000) Nestin expression in embryonic and adult human teeth under normal and pathological conditions. Am J Pathol 157(1):287–295
Bakopoulou A, Leyhausen G, Volk J, Tsiftsoglou A, Garefis P, Koidis P, Geurtsen W (2011) Comparative analysis of in vitro osteo/odontogenic differentiation potential of human dental pulp stem cells (DPSCs) and stem cells from the apical papilla (SCAP). Arch Oral Biol 56:709–721
Couble ML, Farges JC, Bleicher F, Perrat-Mabillon B, Boudeulee M, Magloire H (2000) Odontoblast differentiation of human dental pulp cells in explant cultures. Calcif Tissue Inter 66:129–138
Huang GT, Shagramanova K, Chan SW (2006) Formation of odontoblast-like cells from cultured human dental pulp cells on dentin in vitro. J Endod 32:1066–1073
Lindroos B, Mäenpää K, Ylikomi T, Oia H, Suuronen R, Miettinen S (2008) Characterisation of human dental stem cells and buccal mucosa fibroblasts. Biochem Biophys Res Commun 368:329–335
Mangano C, De Rosa A, Desiderio V, d’Aquino R, Piattelli A, De Francesco F, Tirino V, Mangano F, Papaccio G (2010) The osteoblastic differentiation of dental pulp stem cells and bone formation on different titanium surface textures. Biomaterials 31:3543–3551
Kanafi MM, Ramesh A, Gupta PK, Bhonde RR (2014) Dental pulp stem cells immobilized in alginate microspheres for applications in bone tissue engineering. Int Endod J 47(7):687–697
Akkouch A, Zhang Z, Rouabhia M (2014) Engineering bone tissue using human dental pulp stem cells and an osteogenic collagen-hydroxyapatite-poly(-lactide-co-ε-caprolactone) scaffold. J Biomater Appl 28(6):922–936
El-Backly RM, Massoud AG, El-Badry AM, Sherif RA, Marei MK (2008) Regeneration of dentine/pulp-like tissue using a dental pulp stem cell/poly (lactic-co-glycolic) acid scaffold construct in New Zealand white rabbits. Aust Endod J 34:52–67
Batouli S, Miura M, Brahim J, Tsutsui TW, Fisher LW, Gronthos S, Gehron Robey P, Shi S (2003) Comparison of stem-cell-mediated osteogenesis and dentinogenesis. J Dent Res 82:976–981
Chan B, Wong RW, Rabie B (2011) In vivo production of mineralized tissue pieces for clinical use: a qualitative pilot study using human dental pulp cells. Int J Oral Maxillofac Surg 40:612–620
Graziano A, d’Aquino R, Laino G, Papaccio G (2008) Dental pulp stem cells: a promising tool for bone regeneration. Stem Cell Rev 4:21–26
La Noce M, Paino F, Spina A, Naddeo P, Montella R, Desiderio V, De Rosa A, Papaccio G, Tirino V, Laino L (2014) Dental pulp stem cells: state of the art and suggestions for a true translation of research into therapy. J Dent 42:761–768
Li JH, Liu DY, Zhang FM, Wang F, Zhang WK, Zhang ZT (2011) Human dental pulp stem cell is a promising autologous seed cell for bone tissue engineering. Chin Med J 124:4022–4028
Morito A, Kida Y, Suzuki K, Inoue K, Kuroda N, Gomi K, Arai T, Sato T (2009) Effects of basic fibroblast growth factor on the development of the stem cell properties of human dental pulp cells. Arch Histol Cytol 72:51–64
Yang X, Walboomers XF, Van den Beucken JJ, Bian Z, Fan M, Jansen JA (2009) Hard tissue formation of STRO-1-selected rat dental pulp stem cells in vivo. Tissue Eng Part A 15(2):367–375
Zhang W, Walboomers XF, van Osch GJ, van der Dolder J, Jansen JA (2008) Hard tissue formation in a porous HA/TCP ceramic scaffold loaded with stromal cells derived from dental pulp and bone marrow. Tissue Eng Part A 14:285–294
Ikeda H, Sumita Y, Ikeda M, Ikeda H, Okumura T, Sakai E, Nishimura M, Asahina I (2011) Engineering bone formation from human dental pulp-and periodontal ligament-derived cells. Ann Biomed Eng 39:26–34
Tatullo M, Marrelli M, Shakesheff KM, White LJ (2014) Dental pulp stem cells: function, isolation and applications in regenerative medicine. J Tissue Eng Regen Med. doi:10.1002/term.1899
Yang X, van der Kraan PM, Bian Z, Fan M, Walboomers XF, Jansen JA (2009) Mineralized tissue formation by BMP-2-transfected pulp stem cells. J Dent Res 88(11):1020–1025
Morad G, Kheiri L, Khojasteh A (2013) Dental pulp stem cells for in vivo bone regeneration: a systematic review of literature. Arch Oral Biol 58:1818–1827
Giuliani A, Manescu A, Langer M, Rustichelli F, Desiderio V, Paino F, De Rosa A, Laino L, d’Aquino R, Tirino V, Papaccio G (2013) Three years after transplants in human mandibles, histological and in-line holotomography revealed that stem cells regenerated a compact rather than a spongy bone: biological and clinical implications. Stem Cells Transl Med 2:316–324
Graziano A, d’Aquino R, Laino G, Proto A, Giuliano MT, Pirozzi G, De Rosa A, Di Napoli D, Papaccio G (2008) Human CD34+ stem cells produce bone nodules in vivo. Cell Prolif 41:1–11
Yasui T, Mabuchi Y, Toriumi H, Ebine T, Niibe K, Hoolihan DD, Morikawa S, Onizawa K, Kawana H, Akazawa C, Suzuki N, Nakagawa T, Okano H, Matsuzaki Y (2015) Purified human dental pulp stem cells promote osteogenic regeneration. J Dent Res. doi:10.1177/0022034515610748
Liu L, Ling J, Wei X, Wu L, Xiao Y (2009) Stem cell regulatory gene expression in human adult dental pulp and periodontal ligament cells undergoing odontogenic/osteogenic differentiation. J Endod 35:1368–1376
Ferro F, Spelat R, Beltrami AP, Cesselli D, Curcio F (2012) Isolation and characterization of human dental pulp derived stem cells by using media containing low human serum percentage as clinical grade substitutes for bovine serum. PLoS One 7, e48945
Pisciotta A, Riccio M, Carnevale G, Beretti F, Gibellini L, Maraldi T, Cavallini GM, Ferrari A, Bruzzesi G, De Pol A (2012) Human serum promotes osteogenic differentiation of human dental pulp cells in vitro and in vivo. PLoS One 7, e50542
Al-Habib M, Yu Z, Huang GT (2013) Small molecules affect human dental pulp stem cell properties via multiple signaling pathways. Stem Cells Dev 22(17):2402–2413
Lee SY, Chiang PC, Tsai YH, Tsai SY, Jeng JH, Kawata T, Huang HM (2010) Effects of cryopreservation of intact teeth on the isolated dental pulp stem cells. J Endod 36:1336–1340
Woods EJ, Perry BC, Hockema JJ, Larson L, Zhou D, Goebel WS (2009) Optimized cryopreservation method for human dental-pulp derived stem cells and their tissues of origin for banking and clinical use. Cryobiology 59:150–157
Zhang W, Walboomers XF, Shi S, Fan M, Jansen JA (2006) Multilineage differentiation potential of stem cells derived from human dental pulp after cryopreservation. Tissue Eng 12:2813–2823
Laino G, Carinci F, Graziano A, d’Aquino R, Lanza V, De Rosa A, Gombos F, Caruso F, Guida L, Rullo R, Menditti D, Papaccio G (2006) In vitro bone production using stem cells derived from human dental pulp. J Craniofac Surg 17(3):511–515
Papaccio G, Graziano A, d’Aquino R, Graziano MF, Pirozzi G, Menditti D, de Rosa A, Carinci F, Laino G (2006) Long-term cryopreservation of dental pulp stem cells (SBP-DPSCs) and their differentiated osteoblasts: a cell source for tissue repair. J Cell Physiol 208:319–325
Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, Shi S (2003) SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A 100:5807–5812
Cordeiro MM, Dong Z, Kaneko T, Zhang Z, Miyazawa M, Shi S, Smith AJ, Nör JE (2008) Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth. J Endod 34:962–969
Daltoé FP, Mendonça PP, Mantesso A, Deboni MCZ (2014) Can SHED or DPSCs be used to repair/regenerate non-dental tissues? A systematic review of in vivo studies. Braz Oral Res 28:1–7
Ishkitiev N, Yeagaki K, Calenic B, Nakahara T, Ishikawa H, Mitiev V, Haapasalo M (2010) Deciduous and permanent dental pulp mesenchymal cells acquire hepatic morphologic and functional features in vitro. J Endod 36:469–474
Kerkis I, Kerkis A, Dozortsev D, Stukart-Parsons GC, Gomes Massironi SM, Pereira LV, Caplan AI, Cerruti HF (2006) Isolation and characterization of a population of immature dental pulp stem cells expressing OCT-4 and other embryonic stem cell markers. Cells Tissues Organs 184:105–116
Zhao H, Chai Y (2015) Stem cells in teeth and craniofacial bones. J Dent Res 94(11):1495–1501
Casagrande L, Demarco FF, Zhang Z, Araujo FB, Shi S, Nör JE (2010) Dentin-derived BMP-2 and odontoblast differentiation. J Dent Res 89:603–608
Demarco FF, Casagrande L, Zhang Z, Dong Z, Tarquinio SB, Zeitlin BD, Shi S, Smith AJ, Nör JE (2010) Effects of morphogen and scaffold porogen on the differentiation of dental pulp stem cells. J Endod 36:1805–1811
Galler KM, Cavender AC, Koeklue U, Suggs LJ, Schmaltz G, D’Souza RN (2011) Bioengineering of dental stem cells in a PEGylated fibrin gel. Regen Med 6:191–200
Sakai VT, Zhang Z, Dong Z, Neiva K, Machado Μ, Shi S, Santos C, Nör JE (2010) SHED differentiate into functional odontoblasts and endothelium. J Dent Res 89:791–796
Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, Liu H, Gronthos S, Wang CY, Shi S (2006) Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS One 1, e79
Sonoyama W, Liu Y, Yamaza T, Tuan RS, Wang S, Shi S, Huang GT (2008) Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. J Endod 34:166–171
Huang GT, Gronthos S, Shi S (2009) Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res 88:792–806
Huang GT, Yamaza T, Shea LD, Djouad F, Kuhn NZ, Tuan RS, Shi S (2010) Stem/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model. Tissue Eng Part A 16:605–615
Yagyuu T, Ikeda E, Ohgushi H, Tadokoro M, Hirose M, Maeda M, Inagake K, Kirita T (2010) Hard-tissue forming potential of stem/progenitor cells in human dental follicle and dental papilla. Arch Oral Biol 55:68–76
Morsczeck C, Moehl C, Götz W, Heredia A, Schäffer TE, Eckstein N, Sippel C, Hoffmann KH (2005) In vitro differentiation of human dental follicle cells with dexamethasone and insulin. Cell Biol Int 29:567–575
Estrela C, Alencar AH, Kitten GT, Vencio EF, Gava E (2011) Mesenchymal stem cells in the dental tissues: perspectives for tissue regeneration. Braz Dent J 22:91–98
Vollkommer T, Gosau M, Felthaus O, Reichert TE, Morsczeck C, Gotz W (2015) Genome-wide gene expression profiles of dental follicle stem cells. Acta Odontol Scand 73:93–100
Ikeda E, Yagi K, Kojima M, Yaguu T, Ohshima A, Sobajima S, Tadokoro M, Katsube Y, Isoda K, Kondoh M, Kawase M, Go MJ, Adachi H, Yokota Y, Kirita T, Ohgushi H (2008) Multipotent cells from the human third molar: feasibility of cell-based therapy for liver disease. Differentiation 76:495–505
Kémoun P, Laurencin-Dalicieux S, Rue J, Farges JC, Gennero I, Conte-Auriol F, Briand-Mesange F, Gadelorge M, Arzate H, Narayanan AS, Brunel G, Salles JP (2007) Human dental follicle cells acquire cementoblast features under stimulation by BMP-2/-7 and enamel matrix derivatives (EMD) in vitro. Cell Tissue Res 329:283–294
Völlner F, Ernst W, Driemel O, Morsczeck C (2009) A two-step strategy for neuronal differentiation in vitro of human dental follicle cells. Differentiation 77:433–441
Yalvac ME, Ramazanoglu M, Rizvanov AA, Sahin F, Bayrak OF, Salli U, Palotás A, Kose GT (2010) Isolation and characterization of stem cells derived from human third molar tooth germs of young adults: implications in neo-vascularization, osteo-, adipo- and neurogenesis. Pharmacogenomics J 10:105–113
Lin NH, Gronthos S, Bartold PM (2009) Stem cells and future periodontal regeneration. Periodontol 2000 51:239–251
Morsczeck C, Gotz W, Schierholz J, Zeilhofer F, Kuhn U, Mohl C, Sippel C, Hoffmann KH (2005) Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol 24:155–165
Handa K, Saito M, Tsunoda A, Yamauchi M, Hattori S, Sato S, Toyoda M, Teranaka T, Narayanan AS (2002) Progenitor cells from dental follicle are able to form cementum matrix in vivo. Connect Tissue Res 43:406–408
Yokoi T, Saito M, Kiyono T, Iseki S, Kosaka K, Nishida E, Tsubakimoto T, Harada H, Eto K, Noguchi T, Teranaka T (2007) Establishment of immortalized dental follicle cells for regenerating periodontal ligament in vivo. Cell Tissue Res 327:301–311
Morsczeck C, Schmaltz G, Reichert T, Völlner F, Galler K, Driemel O (2008) Somatic stem cells for regenerative dentistry. Clin Oral Investig 12:113–118
Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, Young M, Gehron Robey P, Wang CY, Shi S (2004) Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364:149–155
Wada N, Menicanin D, Shi S, Bartold PM, Gronthos S (2009) Immunomodulatory properties of human periodontal ligament stem cells. J Cell Physiol 219:667–676
Gault P, Black A, Romette JL, Fuente F, Schroeder K, Thillou F, Brune T, Berdal A, Wurtz T (2010) Tissue-engineered ligament: implant constructs for tooth replacement. J Clin Periodontol 37:750–758
Gay IC, Chen S, MacDougall M (2007) Isolation and characterization of multipotent human periodontal ligament stem cells. Orthod Craniofac Res 10:149–160
Gronthos S, Mrozik K, Shi S, Bartold PM (2006) Ovine periodontal ligament stem cells: isolation, characterization and differentiation potential. Calcif Tissue Int 79:310–317
Menicanin D, Mrozik KM, Wada N, Marino V, Shi S, Bartold PM, Gronthos S (2014) Periodontal-ligament-derived stem cells exhibit the capacity for long-term survival, self-renewal and regeneration of multiple tissue types in vivo. Stem Cells Dev 23:1001–1011
Xu J, Wang W, Kapila Y, Lotz J, Kapila S (2009a) Multiple differentiation capacity of STRO-1+/CD146+ PDL mesenchymal progenitor cells. Stem Cells Dev 18(3):487–496
Shi S, Bartold PM, Miura M, Seo BM, Robey PG, Gronthos S (2005) The efficacy of mesenchymal stem cells to regenerate and repair dental structures. Orthod Craniofac Res 8:191–199
Trubiani O, Orsini G, Zini N, Di Iorio D, Piccirilli M, Piattelli A, Caputi S (2008) Regenerative potential of human periodontal ligament derived stem cells on three-dimensional biomaterials: a morphological report. J Biomed Mater Res A 00087:986–993
He H, Yu J, Cao J, E LL, Wang D, Zhang H, Liu H (2011) Biocompatibility and osteogenic capacity of periodontal ligament stem cells on nHAC/PLA and HA/TCP scaffolds. J Biomater Sci Polym Ed 22:179–194
Marynka-Kalmani K, Treves S, Yafee M, Rachima H, Gafni Y, Cohen MA, Pitaru S (2010) The lamina propria of adult human oral mucosa harbors a novel stem cell population. Stem Cells 28:984–995
Tang L, Li N, Xie H, Jin Y (2011) Characterization of mesenchymal stem cells from human normal and hyperplastic gingiva. J Cell Physiol 226:832–842
Zhang Q, Shi S, Liu Y, Uyanne J, Shi S, Le AD (2009) Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis. J Immunol 183:7787–7798
Tomar GB, Srivastava RK, Gupta N, Barhanpurkar AP, Pote ST, Jhaveri HM, Mishra GC, Wani MR (2010) Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine. Biochem Biophys Res Commun 393:377–383
Moshaverinia A, Chen C, Xu X, Akiyama K, Ansari S, Zadeh HH, Shi S (2014) Bone regeneration potential of stem cells derived from periodontal ligament or gingival tissue sources encapsulated in RGD-modified alginate scaffold. Tissue Eng Part A 20:611–621
Matsubara T, Suardita K, Ishii M, Sugiyama M, Igarashi A, Oda R, Nishimura M, Saito M, Nkagawa K et al (2005) Alveolar bone marrow as a cell source for regenerative medicine: differences between alveolar and iliac bone marrow stromal cells. J Bone Miner Res 20(3):399–409
Mason S, Tarle S, Osibin W, Kinfu Y, Kaigler D (2014) Standardization and safety of alveolar bone-derived stem cell isolation. J Dent Res 33:55–61
Park J, Kim JC, Kim YT, Choi SH, Cho KS, Im GI, Kim BS, Kim CS (2012) Acquisition of human alveolar bone-derived stromal cells using minimally irrigated implant osteotomy: in vitro and in vivo evaluations. J Clin Periodontol 39:495–505
Kim BS, Kim JS, Chung YS, Sin YW, Ryu KH, Lee J, You HK (2013) Growth and osteogenic differentiation of alveoral human bone marrow-derived mesenchymal stem cells on chitosan/hydroxyapatite composite fabric. J Biomed Mater Res A 101:1550–1558
Arkell RM, Tam PPL (2012) Signalling and transcriptional activity: initiating head development in mouse embryos: integrating. Open Biol 2(3):120030
Noden DM, Trainor PA (2005) Relations and interactions between cranial mesoderm and neural crest populations. J Anat 207(5):575–601
Behr B, Panetta NJ, Longaker MT, Quarto N (2010) Different endogenous threshold levels of fibroblast growth factor-ligands determine the healing potential of frontal and parietal bones. Bone 47(2):281–294
Senarath-Yapa K, Li S, Meyer NP, Longaker MT, Quarto N (2013) Integration of multiple signaling pathways determines differences in the osteogenic potential and tissue regeneration of neural crest-derived and mesoderm-derived calvarial bones. Int J Mol Sci 14(3):5978–5997
Greenwald AS, Boden SD, Goldberg VM, Khan Y, Laurencin CT, Rosier RN (2001) Bone-graft substitutes: facts, fictions and applications. J Bone Joint Surg Am 83A(Suppl 2 Pt 2):98–103
Dinopoulos H, Dimitriou R, Giannoudis PV (2012) Bone graft substitutes: what are the options? Surgeon 10(4):230–239
Mao JJ, Giannobile WV, Helms JA, Hollister SJ, Krebsbach PH, Longaker MT, Shi S (2006) Craniofacial tissue engineering by stem cells. J Dent Res 85(11):966–979
Zaky SH, Cancedda R (2009) Engineering craniofacial structures: facing the challenge. J Dent Res 88(12):1077–1091
Muschler GF, Raut VP, Patterson TE, Wenke JC, Hollinger JO (2010) The design and use of animal models for translational research in bone tissue engineering and regenerative medicine. Tissue Eng Part B Rev 16(1):123–145
Gomes PS, Fernandes MH (2011) Rodent models in bone-related research: the relevance of calvarial defects in the assessment of bone regeneration strategies. Lab Anim 45(1):14–24
An Y, Friedman R (1999) Animal models of bone defect repair. In: An Y, Friedman R (eds) Animal models in orthopaedic research. CRC Press, Boca Raton, pp 241–260
Frame JW (1980) A convenient animal model for testing bone substitute materials. J Oral Surg 38(3):176–180
Honma T, Itagaki T, Nakamura M, Kamakura S, Takahashi I, Echigo S, Sasano Y (2008) Bone formation in rat calvaria ceases within a limited period regardless of completion of defect repair. Oral Dis 14(5):457–464
Liebschner M (2004) Biomechanical considerations of animal models used in tissue engineering of bone. Biomaterials 25(9):1697–1714
Mooney MP, Siegel MI (2005) Animal models for bone tissue engineering. In: Wnek G, Bowlin G (eds) Encyclopedia of biomaterials and biomedical engineering. Marcel Dekker, New York, pp 1–19
Schmitz JP, Hollinger JO (1986) The critical size defect as an experimental model for craniomandibulofacialnonunions. Clin Orthop Relat Res 205:299–308
Hollinger JO, Kleinschmidt JC (1990) The critical size defect as an experimental model to test bone repair materials. J Craniofac Surg 1(1):60–68
Bosch C, Melsen B, Vargervik K (1998) Importance of the critical-size bone defect in testing bone-regenerating materials. J Craniofac Surg 9(4):310–316
Petridis X, Diamanti E, Trigas GC, Kalyvas D, Kitraki E (2015) Bone regeneration in critical-size calvarial defects using human dental pulp cells in an extracellular matrix-based scaffold. J Craniomaxillofac Surg 43(4):483–490
Cooper GM, Mooney MP, Gosain AK, Campbell PG, Losee JE, Huard J (2010) Testing the critical size in calvarial bone defects: revisiting the concept of a critical-size defect. Plast Reconstr Surg 125(6):1685–1692
Chai Y, Jiang X, Ito Y, Bringas P Jr, Han J, Rowitch DH, Soriano P, McMahon AP, Sukov HM (2000) Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. Development 127(8):1671–1679
Riccio M, Resca E, Maraldi T et al (2010) Human dental pulp stem cells produce mineralized matrix in 2D and 3D cultures. Eur J Histochem 54(4), e46
Maraldi T, Riccio M, Pisciotta A, Zavatti M, Carnevale G, Beretti F, La Sala GB, Motta A, De Pol A (2013) Human amniotic fluid-derived and dental pulp derived stem cells seeded into collagen scaffold repair critical-size bone defects promoting vascularization. Stem Cell Res Ther 4:53
Riccio M, Maraldi T, Pisciotta A, La Sala GB, Ferrari A, Bruzzesi G, Motta A, Migliaresi C, De Pol A (2012) Fibroin scaffold repairs critical-size bone defects in vivo supported by human amniotic fluid and dental pulp stem cells. Tissue Eng Part A 18(9–10):1006–1013
Su Y, Shi S, Liu Y (2014) Immunomodulation regulates mesenchymal stem cell-based bone regeneration. Oral Dis 20(7):633–636
Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98(5):1076–1084
O’Brien FJ (2011) Biomaterials and scaffolds for tissue engineering. Mater Today 14(3):88–95
Murphy CM, O’Brien FJ, Little DG, Schindeler A (2013) Cell-scaffold interactions in the bone tissue engineering triad. Eur Cell Mater 26:120–132
Alhag M, Farrell E, Toner M, Claffey N, Lee TC, O’Brien FJ (2011) Evaluation of early healing events around mesenchymal stem cell-seeded collagen–glycosaminoglycan scaffold. An experimental study in Wistar rats. Oral Maxillofac Surg 15:31–39
Alhag M, Farrell E, Toner M, Clive Lee T, O’Brien FJ, Claffey N (2012) Evaluation of the ability of collagen–glycosaminoglycan scaffolds with or without mesenchymal stem cells to heal bone defects in Wistar rats. Oral Maxillofac Surg 16:47–55
de Mendonça Costa A, Bueno DF, Martins MT, Kerkis I, Kerkis A, Fanganiello RD, Cerutti A, Alonso N, Passos-Bueno MR (2008) Reconstruction of large cranial defects in nonimmunosuppressed experimental design with human dental pulp stem cells. J Craniofac Surg 19(1):204–210
Ma L, Makino Y, Yamaza H, Akiyama K, Hoshino Y, Song G, Kukita T, Nonaka K, Shi S, Yamaza T (2012) Cryopreserved dental pulp tissues of exfoliated deciduous teeth is a feasible stem cell resource for regenerative medicine. PLoS One 7(12), e51777
Seo BM, Sonoyama W, Yamaza T, Coppe C, Kikuiri T, Akiyama K, Lee JS, Shi S (2008) SHED repair critical-size calvarial defects in mice. Oral Dis 14(5):428–434
Ge S, Zhao N, Wang L, Yu M, Liu H, Song A, Huang J, Wang G, Yang P (2012) Bone repair by periodontal ligament stem cellseeded nanohydroxyapatite-chitosan scaffold. Int J Nanomedicine 7:5405–5414
Tour G, Wendel M, Moll G, Tcacencu I (2012) Bone repair using periodontal ligament progenitor cell-seeded constructs. J Dent Res 91(8):789–794
Honda MJ, Imaizumi M, Suzuki H, Ohshima S, Tsuchiya S, Satomura K (2011) Stem cells isolated from human dental follicles have osteogenic potential. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 111(6):700–708
Pearce AI, Richards RG, Milz S, Schneider E, Pearce SG (2007) Animal models for implant biomaterial research in bone: a review. Eur Cell Mater 13:1–10
Liu HC, E LL, Wang DS, Su F, Wu X, Shi ZP, Lv Y, Wang JZ (2011) Reconstruction of alveolar bone defects using bone morphogenetic protein 2 mediated rabbit dental pulp stem cells seeded on nano-hydroxyapatite/collagen/poly(L-lactide). Tissue Eng Part A 17(19–20): 2417–2433
Yamada Y, Ito K, Nakamura S, Ueda M, Nagasaka T (2011) Promising cell-based therapy for bone regeneration using stem cells from deciduous teeth, dental pulp, and bone marrow. Cell Transplant 20(7):1003–1013
Zheng Y, Liu Y, Zhang CM, Zhang HY, Li WH, Shi S, Le AD, Wang SL (2009) Stem cells from deciduous tooth repair mandibular defect in swine. J Dent Res 88(3):249–254
Kuo TF, Lee SY, Wu HD, Poma M, Wu YW, Yang JC (2015) An in vivo swine study for xeno-grafts of calcium sulfate-based bone grafts with human dental pulp stem cells (hDPSCs). Mater Sci Eng C Mater Biol Appl 50:19–23
Alkaisi A, Ismail AR, Mutum SS, Ahmad ZA, Masudi S, Abd Razak NH (2013) Transplantation of human dental pulp stem cells: enhance bone consolidation in mandibular distraction osteogenesis. J Oral Maxillofac Surg 71(10):1758.e1-13
d’Aquino R, De Rosa A, Lanza V, Tirino V, Laino L, Graziano A, Desiderio V, Laino G, Papaccio G (2009) Human mandible bone defect repair by the grafting of dental pulp stem/progenitor cells and collagen sponge biocomplexes. Eur Cell Mater 18:75–83
Liu N, Lyu X, Fan H, Shi J, Hu J, Luo E (2014) Animal models for craniofacial reconstruction by stem/stromal cells. Curr Stem Cell Res Ther 9(3):174–186
Caton J, Mota L, Gandini L, Laskaris B (1994) Non-human primate models for testing the efficacy and safety of periodontal regeneration procedures. J Periodontol 65(12):1143–1150
Suaid FF, Ribeiro FV, Gomes TR, Silvério KG, Carvalho MD, Nociti FH Jr, Casati MZ, Sallum EA (2012) Autologous periodontal ligament cells in the treatment of Class III furcation defects: a study in dogs. J Clin Periodontol 39(4):377–384
Tsumanuma Y, Iwata T, Washio K, Yoshida T, Yamada A, Takagi R, Ohno T, Lin K, Yamato M, Ishikawa I, Okano T, Izumi Y (2011) Comparison of different tissue-derived stem cell sheets for periodontal regeneration in a canine 1-wall defect model. Biomaterials 32(25):5819–5825
Han J, Menicanin D, Marino V, Ge S, Mrozik K, Gronthos S, Bartold PM (2014) Assessment of the regenerative potential of allogeneic periodontal ligament stem cells in a rodent periodontal defect model. J Periodontal Res 49(3):333–345
Liu Y, Zheng Y, Ding G, Fang D, Zhang C, Bartold PM, Gronthos S, Shi S, Wang S (2008) Periodontal ligament stem cell-mediated treatment for periodontitis in miniature swine. Stem Cells 26(4):1065–1073
Park JY, Jeon SH, Choung PH (2011) Efficacy of periodontal stem cell transplantation in the treatment of advanced periodontitis. Cell Transplant 20(2):271–285
Ito K, Yamada Y, Nakamura S, Ueda M (2011) Osteogenic potential of effective bone engineering using dental pulp stem cells, bone marrow stem cells, and periosteal cells for osseointegration of dental implants. Int J Oral Maxillofac Implants 26(5):947–954
Kim SH, Kim KH, Seo BM, Koo KT, Kim TI, Seol YJ, Ku Y, Rhyu IC, Chung CP, Lee YM (2009) Alveolar bone regeneration by transplantation of periodontal ligament stem cells and bone marrow stem cells in a canine peri-implant defect model: a pilot study. J Periodontol 80(11):1815–1823
Omori M, Tsuchiya S, Hara K, Kuroda K, Hibi H, Okido M, Ueda M (2015) A new application of cell-free bone regeneration: immobilizing stem cells from human exfoliated deciduous teeth-conditioned medium onto titanium implants using atmospheric pressure plasma treatment. Stem Cell Res Ther 6:124
Asatrian G, Pham D, Hardy WR, James AW, Peault B (2015) Stem cell technology for bone regeneration: current status and potential applications. Stem Cells Cloning 10(8):39–48
Feng F, Akiyama K, Liu Y et al (2010) Utility of PDL progenitors for in vivo tissue regeneration: a report of 3 cases. Oral Dis 16:20–28
Xu LL, Liu HC, Wang DS, E LL, Xu L, Jin ZL, Duan YZ (2009b) Effects of BMP-2 and dexamethasone on osteogenic differentiation of rat dental follicle progenitor cells seeded on three-dimensional beta-TCP. Biomed Mater 4(6):065010
Peric M, Dumic-Cule I, Grcevic D, Matijasic M, Verbanac D, Paul R, Grgurevic L, Trkulja V, Bagi CM, Vukicevic S (2015) The rational use of animal models in the evaluation of novel bone regenerative therapies. Bone 70:73–86
Nakamura A, Akahane M, Shigematsu H, Tadokoro M, Morita Y, Ohgushi H, Dohi Y, Imamura T, Tanaka Y (2010) Cell sheet transplantation of cultured mesenchymal stem cells enhances bone formation in a rat nonunion model. Bone 46:418e24
Yiying QI, Tengfei Z, Weiqi Y, Kan XU, Zhongli S, Jianwei W (2013) Mesenchymal stem cell sheet transplantation combined with locally released simvastatin enhances bone formation in a rat tibia osteotomy model. Cytotherapy 15:44–56
Gómez-Barrena E, Rosset F, Lozano D, Stanovici J, Ermthaller C, Gerbhard F (2015) Bone fracture healing: cell therapy in delayed unions and nonunions. Bone 70:93–101
Sloan AJ, Waddington RJ (2009) Dental pulp stem cells: what, where, how? Int J Paediatr Dent 19(1):61–70
Castano-Izquierdo H, Alvarez-Barreto J, van der Dolder J, Jansen JA, Mikos AG, Sikavitsas VI (2007) Pre-culture period of mesenchymal stem cells in osteogenic media influences their in vivo bone forming potential. J Biomed Mater Res A 82:129–138
Patel M, Smith AJ, Sloan AJ, Smith G, Cooper PR (2009) Phenotype and behaviour of dental pulp cells during expansion culture. Arch Oral Biol 54:898–908
Kitraki E, Zakkas S, Synolaki E, Diamanti E, Tiniakos DG, Stamatakis A, Matsioula C, Stylianopoulou F, Papapolychroniou T (2014) Dental pulp cells enhance bone healing in a rat osteotomy model. Ann Orthop Rheumatol 2(1):1009
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Diamanti, E., Petridis, X., Kaparou, A., Kitraki, E. (2016). Dental Stem Cells for Bone Regeneration. In: Zavan, B., Bressan, E. (eds) Dental Stem Cells: Regenerative Potential. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-33299-4_11
Download citation
DOI: https://doi.org/10.1007/978-3-319-33299-4_11
Published:
Publisher Name: Humana Press, Cham
Print ISBN: 978-3-319-33297-0
Online ISBN: 978-3-319-33299-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)