Dental Pulp Stem Cells: A Promising Tool for Bone Regeneration

Human tissues are different in term of regenerative properties. Stem cells are a promising tool for tissue regeneration, thanks to their particular characteristics of proliferation, differentiation and plasticity. Several “loci” or “niches” within the adult human body are colonized by a significant number of stem cells. However, access to these potential collection sites often is a limiting point. The interaction with biomaterials is a further point that needs to be considered for the therapeutic use of stem cells. Dental pulp stem cells (DPSCs) have been demonstrated to answer all of these issues: access to the collection site of these cells is easy and produces very low morbidity; extraction of stem cells from pulp tissue is highly efficiency; they have an extensive differentiation ability; and the demonstrated interactivity with biomaterials makes them ideal for tissue reconstruction. SBP-DPSCs are a multipotent stem cell subpopulation of DPSCs which are able to differentiate into osteoblasts, synthesizing 3D woven bone tissue chips in vitro and that are capable to synergically differentiate into osteoblasts and endotheliocytes. Several studied have been performed on DPSCs and they mainly found that these cells are multipotent stromal cells that can be safety cryopreserved, used with several scaffolds, that can extensively proliferate, have a long lifespan and build in vivo an adult bone with Havers channels and an appropriate vascularization. A definitive proof of their ability to produce dentin has not been yet done. Interestingly, they seem to possess immunoprivileges as they can be grafted into allogenic tissues and seem to exert anti-inflammatory abilities, like many other mesenchymal stem cells. The easy management of dental pulp stem cells make them feasible for use in clinical trials on human patients.

[1]  J. Thomson,et al.  Embryonic stem cell lines derived from human blastocysts. , 1998, Science.

[2]  J. Chies,et al.  Behavior of human dental pulp cells exposed to transforming growth factor-beta1 and acidic fibroblast growth factor in culture. , 2007, Journal of endodontics.

[3]  S. Gronthos,et al.  Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Darwin J. Prockop,et al.  Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta , 1999, Nature Medicine.

[5]  F. Carinci,et al.  A New Population of Human Adult Dental Pulp Stem Cells: A Useful Source of Living Autologous Fibrous Bone Tissue (LAB) , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  Yun-Hoon Choung,et al.  Isolation and characterization of postnatal stem cells from human dental tissues. , 2007, Tissue engineering.

[7]  A. George,et al.  Dentin matrix protein 1 induces cytodifferentiation of dental pulp stem cells into odontoblasts , 2006, Gene Therapy.

[8]  G. Martin,et al.  Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[9]  T. Takano-Yamamoto,et al.  Runx3 negatively regulates Osterix expression in dental pulp cells. , 2007, The Biochemical journal.

[10]  F. Carinci,et al.  Long‐term cryopreservation of dental pulp stem cells (SBP‐DPSCs) and their differentiated osteoblasts: A cell source for tissue repair , 2006, Journal of cellular physiology.

[11]  F. Arfuso A study of physiologic angiogenesis in the human using the dental pulp as an in vivo model. , 2006, Endothelium : journal of endothelial cell research.

[12]  J. Jansen,et al.  Multilineage differentiation potential of stem cells derived from human dental pulp after cryopreservation. , 2006, Tissue engineering.

[13]  M. Sampaolesi,et al.  Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation , 2007, Cell Death and Differentiation.

[14]  Adriano Piattelli,et al.  Scaffold's surface geometry significantly affects human stem cell bone tissue engineering , 2008, Journal of cellular physiology.

[15]  P. Bianco,et al.  Reproduction of human fibrous dysplasia of bone in immunocompromised mice by transplanted mosaics of normal and Gsalpha-mutated skeletal progenitor cells. , 1998, The Journal of clinical investigation.

[16]  S. Gronthos,et al.  Perivascular Niche of Postnatal Mesenchymal Stem Cells in Human Bone Marrow and Dental Pulp , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[17]  T. Noma,et al.  Soluble matrix from osteoblastic cells induces mineralization by dental pulp cells. , 2006, The journal of medical investigation : JMI.

[18]  Q. Jin,et al.  Current concepts in periodontal bioengineering. , 2005, Orthodontics & craniofacial research.

[19]  P. Bianco,et al.  Stem cells in tissue engineering , 2001, Nature.

[20]  H. Lesot,et al.  Epigenetic Signals during Odontoblast Differentiation , 2001, Advances in dental research.

[21]  M. Fayad,et al.  In vivo generation of dental pulp-like tissue by using dental pulp stem cells, a collagen scaffold, and dentin matrix protein 1 after subcutaneous transplantation in mice. , 2008, Journal of endodontics.

[22]  C. Erickson,et al.  Neural crest development: the interplay between morphogenesis and cell differentiation. , 1998, Current topics in developmental biology.

[23]  Mario Calvitti,et al.  Multipotent Mesenchymal Stem Cells with Immunosuppressive Activity Can Be Easily Isolated from Dental Pulp , 2005, Transplantation.

[24]  J. Nör,et al.  Vascular endothelial growth factor and its relationship with the dental pulp. , 2007, Journal of endodontics.

[25]  L. Olson,et al.  Dental pulp cells produce neurotrophic factors, interact with trigeminal neurons in vitro, and rescue motoneurons after spinal cord injury. , 2001, Developmental biology.

[26]  W. Oh,et al.  Influence of TGF-beta1 on the expression of BSP, DSP, TGF-beta1 receptor I and Smad proteins during reparative dentinogenesis. , 2008, Journal of molecular histology.

[27]  H. Kagami,et al.  Differential Inducibility of Human and Porcine Dental Pulp-Derived Cells into Odontoblasts , 2007, Connective tissue research.

[28]  R. Waddington,et al.  Isolation of Distinct Progenitor Stem Cell Populations from Dental Pulp , 2008, Cells Tissues Organs.

[29]  P H Krebsbach,et al.  Craniofacial Tissue Engineering by Stem Cells , 2006, Journal of dental research.

[30]  J. Nör,et al.  Vascular endothelial growth factor receptor-2 expression in the pulp of human primary and young permanent teeth. , 2007, Journal of endodontics.

[31]  S. Shi,et al.  SHED repair critical-size calvarial defects in mice. , 2008, Oral diseases.

[32]  F. Carinci,et al.  In Vitro Bone Production Using Stem Cells Derived From Human Dental Pulp , 2006, The Journal of craniofacial surgery.

[33]  Yan Jin,et al.  Differentiation of dental pulp stem cells into regular-shaped dentin-pulp complex induced by tooth germ cell conditioned medium. , 2006, Tissue engineering.

[34]  Stan Gronthos,et al.  Investigation of multipotent postnatal stem cells from human periodontal ligament , 2004, The Lancet.

[35]  D. Bosshardt Are Cementoblasts a Subpopulation of Osteoblasts or a Unique Phenotype? , 2005, Journal of dental research.

[36]  B. Clarkson,et al.  Matrix and TGF-β-related gene expression during human dental pulp stem cell (DPSC) mineralization , 2007, In Vitro Cellular & Developmental Biology - Animal.

[37]  A. Akamine,et al.  Dentin Regeneration by Dental Pulp Stem Cell Therapy with Recombinant Human Bone Morphogenetic Protein 2 , 2004, Journal of dental research.

[38]  Y. Kudo,et al.  Immortalization and characterization of human dental pulp cells with odontoblastic differentiation. , 2007, Archives of oral biology.

[39]  J. van den Dolder,et al.  The odontogenic potential of STRO‐1 sorted rat dental pulp stem cells in vitro , 2007, Journal of tissue engineering and regenerative medicine.

[40]  A. Giordano,et al.  The tissue banking in cancer and stem cell research , 2007, Journal of cellular physiology.

[41]  B. Nygaard-Ostby,et al.  Tissue formation in the root canal following pulp removal. , 1971, Scandinavian journal of dental research.

[42]  F. Barry Biology and clinical applications of mesenchymal stem cells. , 2003, Birth defects research. Part C, Embryo today : reviews.

[43]  R. Tuan,et al.  Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. , 2008, Journal of endodontics.

[44]  S. Takeda,et al.  Laminin α2 Is Essential for Odontoblast Differentiation Regulating Dentin Sialoprotein Expression* , 2004, Journal of Biological Chemistry.

[45]  A. Hosoya,et al.  Hard Tissue Formation in Subcutaneously Transplanted Rat Dental Pulp , 2007, Journal of dental research.

[46]  A. Boyde,et al.  Stem Cell Properties of Human Dental Pulp Stem Cells , 2002, Journal of dental research.

[47]  S. Caputi,et al.  Human Dental Pulp Vasculogenesis Evaluated by CD34 Antigen Expression and Morphological Arrangement , 2003, Journal of dental research.

[48]  S. Yıldırım,et al.  The role of dental pulp cells in resorption of deciduous teeth. , 2008, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[49]  S. Yamanaka,et al.  Induction of pluripotent stem cells from fibroblast cultures , 2007, Nature Protocols.

[50]  R. Tuan,et al.  Stem/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model. , 2010, Tissue engineering. Part A.

[51]  S. Valiante,et al.  An approachable human adult stem cell source for hard‐tissue engineering , 2006, Journal of cellular physiology.

[52]  Stan Gronthos,et al.  SHED: Stem cells from human exfoliated deciduous teeth , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[53]  O. Matsuo,et al.  Mesenchymal progenitor cells in adult human dental pulp and their ability to form bone when transplanted into immunocompromised mice , 2007, Cell biology international.

[54]  T. Sugaya,et al.  Effect of recombinant human platelet-derived growth factor-BB and bone morphogenetic protein-2 application to demineralized dentin on early periodontal ligament cell response. , 1999, Journal of periodontal research.

[55]  Mark P. Lewis,et al.  Human adult craniofacial muscle‐derived cells: neural‐cell adhesion‐molecule (NCAM; CD56)‐expressing cells appear to contain multipotential stem cells , 2004, Biotechnology and applied biochemistry.

[56]  Yin Xiao,et al.  Expression of mineralization markers in dental pulp cells. , 2007, Journal of endodontics.

[57]  J. van den Dolder,et al.  Multilineage potential of STRO‐1+ rat dental pulp cells in vitro , 2007, Journal of tissue engineering and regenerative medicine.

[58]  S. Gronthos,et al.  Comparison of Stem-cell-mediated Osteogenesis and Dentinogenesis , 2003, Journal of dental research.

[59]  Haiyang Huang,et al.  Identification of the haematopoietic stem cell niche and control of the niche size , 2003, Nature.

[60]  I. Kerkis,et al.  Isolation and Characterization of a Population of Immature Dental Pulp Stem Cells Expressing OCT-4 and Other Embryonic Stem Cell Markers , 2007, Cells Tissues Organs.

[61]  P. Pavasant,et al.  Different roles of dexamethasone on transforming growth factor-beta1-induced fibronectin and nerve growth factor expression in dental pulp cells. , 2007, Journal of endodontics.

[62]  J. Nör Tooth regeneration in operative dentistry. , 2006, Operative dentistry.

[63]  S. Mathieu,et al.  Role of Human Pulp Fibroblasts in Angiogenesis , 2006, Journal of dental research.

[64]  K. Matsushita,et al.  Side Population Cells Isolated from Porcine Dental Pulp Tissue with Self‐Renewal and Multipotency for Dentinogenesis, Chondrogenesis, Adipogenesis, and Neurogenesis , 2006, Stem cells.

[65]  S. Gronthos,et al.  Stem cells and future periodontal regeneration. , 2009, Periodontology 2000.

[66]  M. Kaufman,et al.  Establishment in culture of pluripotential cells from mouse embryos , 1981, Nature.

[67]  S. Shi,et al.  Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth. , 2008, Journal of endodontics.

[68]  H. C. Beck,et al.  Proteomic analysis of osteogenic differentiation of dental follicle precursor cells , 2009, Electrophoresis.

[69]  A. Piattelli,et al.  Concave Pit-Containing Scaffold Surfaces Improve Stem Cell-Derived Osteoblast Performance and Lead to Significant Bone Tissue Formation , 2007, PloS one.

[70]  P. Bianco,et al.  Mesenchymal stem cells: revisiting history, concepts, and assays. , 2008, Cell stem cell.

[71]  John A Jansen,et al.  The performance of human dental pulp stem cells on different three-dimensional scaffold materials. , 2006, Biomaterials.

[72]  S. Shi,et al.  Recovery of Stem Cells from Cryopreserved Periodontal Ligament , 2005, Journal of dental research.

[73]  W. Oh,et al.  Influence of TGF-β1 on the expression of BSP, DSP, TGF-β1 receptor I and Smad proteins during reparative dentinogenesis , 2008, Journal of Molecular Histology.

[74]  N. Zini,et al.  Regenerative potential of human periodontal ligament derived stem cells on three-dimensional biomaterials: a morphological report. , 2008, Journal of biomedical materials research. Part A.

[75]  R. Rullo,et al.  Human dental pulp stem cells: from biology to clinical applications. , 2009, Journal of experimental zoology. Part B, Molecular and developmental evolution.