Abstract
The advent of regenerative medicine has brought us the opportunity to regenerate, modify and restore human organs function. Stem cells, a key resource in regenerative medicine, are defined as clonogenic, self-renewing, progenitor cells that can generate into one or more specialized cell types. Stem cells have been classified into three main groups: embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult/postnatal stem cells (ASCs). The present review focused the attention on ASCs, which have been identified in many perioral tissues such as dental pulp, periodontal ligament, follicle, gingival, alveolar bone and papilla. Human dental pulp stem cells (hDPSCs) are ectodermal-derived stem cells, originating from migrating neural crest cells and possess mesenchymal stem cell properties. During last decade, hDPSCs have received extensive attention in the field of tissue engineering and regenerative medicine due to their accessibility and ability to differentiate in several cell phenotypes. In this review, we have carefully described the potential of hDPSCs to differentiate into odontoblasts, osteocytes/osteoblasts, adipocytes, chondrocytes and neural cells.
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Sedgley, C. M., & Botero, T. M. (2012). Dental stem cells and their sources. Dental Clinics of North America, 56(3), 549–561.
Rodriguez-Lozano, F. J., et al. (2011). Mesenchymal stem cells derived from dental tissues. International Endodontic Journal, 44(9), 800–806.
Moraleda, J. M., et al. (2006). Adult stem cell therapy: dream or reality? Transplant Immunology, 17(1), 74–77.
Suchanek, J., et al. (2007). Human dental pulp stem cells—isolation and long term cultivation. Acta Medica (Hradec Králové), 50(3), 195–201.
Berardi, A. C., et al. (1995). Functional isolation and characterization of human hematopoietic stem cells. Science, 267(5194), 104–108.
Jones, P. H., Harper, S., & Watt, F. M. (1995). Stem cell patterning and fate in human epidermis. Cell, 80(1), 83–93.
Owen, M. (1988). Marrow stromal stem cells. Journal of Cell Science. Supplement, 10, 63–76.
Bobis, S., Jarocha, D., & Majka, M. (2006). Mesenchymal stem cells: characteristics and clinical applications. Folia Histochemica et Cytobiologica, 44(4), 215–230.
Rietze, R. L., & Reynolds, B. A. (2006). Neural stem cell isolation and characterization. Methods in Enzymology, 419, 3–23.
Tseng, S. C. (1989). Concept and application of limbal stem cells. Eye (London, England), 3(Pt 2), 141–157.
Funderburgh, J.L., Funderburgh, M.L., & Du, Y. (2016). Stem cells in the Limbal Stroma. The Ocular Surface.
Sell, S. (1994). Liver stem cells. Modern Pathology, 7(1), 105–112.
Pittenger, M. F., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284(5411), 143–147.
Mareschi, K., et al. (2001). Isolation of human mesenchymal stem cells: bone marrow versus umbilical cord blood. Haematologica, 86(10), 1099–1100.
Zuk, P. A., et al. (2001). Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Engineering, 7(2), 211–228.
Li, M., & Ikehara, S. (2013). Bone-marrow-derived mesenchymal stem cells for organ repair. Stem Cells International, 2013, 132642.
Otabe, K., et al. (2015). Transcription factor Mohawk controls tenogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo. Journal of Orthopaedic Research, 33(1), 1–8.
Huang, G. T., Gronthos, S., & Shi, S. (2009). Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. Journal of Dental Research, 88(9), 792–806.
Chatterjee, K. (2006). Essentials of oral histology. Jaypee Brothers, Medical Publishers Pvt. Limited.
Ranganathan, K., & Lakshminarayanan, V. (2012). Stem cells of the dental pulp. Indian Journal of Dental Research, 23(4), 558.
Gronthos, S., et al. (2000). Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America, 97(25), 13625–13630.
Miura, M., et al. (2003). SHED: stem cells from human exfoliated deciduous teeth. Proceedings of the National Academy of Sciences of the United States of America, 100(10), 5807–5812.
Seo, B. M., et al. (2005). Recovery of stem cells from cryopreserved periodontal ligament. Journal of Dental Research, 84(10), 907–912.
Morsczeck, C., et al. (2005). Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biology, 24(2), 155–165.
Sonoyama, W., et al. (2006). Mesenchymal stem cell-mediated functional tooth regeneration in swine. PloS One, 1, e79.
Zhang, Q., et al. (2009). Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis. Journal of Immunology, 183(12), 7787–7798.
Liu, J., et al. (2015). Concise reviews: characteristics and potential applications of human dental tissue-derived mesenchymal stem cells. Stem Cells, 33(3), 627–638.
Kumar, G.S. (2014). Orban’s oral histology & embryology. Elsevier Health Sciences APAC.
Nanci, A. (2014). Ten Cate’s oral histology: development, structure, and function. Elsevier Health Sciences.
Martens, W., et al. (2013). Dental stem cells and their promising role in neural regeneration: an update. Clinical Oral Investigations, 17(9), 1969–1983.
Fawzy El-Sayed, K. M., et al. (2013). Adult mesenchymal stem cells explored in the dental field. Advances in Biochemical Engineering and Biotechnology, 130, 89–103.
Alge, D. L., et al. (2010). Donor-matched comparison of dental pulp stem cells and bone marrow-derived mesenchymal stem cells in a rat model. Journal of Tissue Engineering and Regenerative Medicine, 4(1), 73–81.
Govindasamy, V., et al. (2011). Differentiation of dental pulp stem cells into islet-like aggregates. Journal of Dental Research, 90(5), 646–652.
Gandia, C., et al. (2008). Human dental pulp stem cells improve left ventricular function, induce angiogenesis, and reduce infarct size in rats with acute myocardial infarction. Stem Cells, 26(3), 638–645.
Monteiro, B. G., et al. (2009). Human immature dental pulp stem cells share key characteristic features with limbal stem cells. Cell Proliferation, 42(5), 587–594.
Gomes, J. A., et al. (2010). Corneal reconstruction with tissue-engineered cell sheets composed of human immature dental pulp stem cells. Investigative Ophthalmology & Visual Science, 51(3), 1408–1414.
Shi, S., Robey, P. G., & Gronthos, S. (2001). Comparison of human dental pulp and bone marrow stromal stem cells by cDNA microarray analysis. Bone, 29(6), 532–539.
Huang, G. T., Shagramanova, K., & Chan, S. W. (2006). Formation of odontoblast-like cells from cultured human dental pulp cells on dentin in vitro. Journal of Endodontics, 32(11), 1066–1073.
Batouli, S., et al. (2003). Comparison of stem-cell-mediated osteogenesis and dentinogenesis. Journal of Dental Research, 82(12), 976–981.
Alongi, D. J., et al. (2010). Stem/progenitor cells from inflamed human dental pulp retain tissue regeneration potential. Regenerative Medicine, 5(4), 617–631.
Davies, O. G., et al. (2015). A comparison of the in vitro mineralisation and dentinogenic potential of mesenchymal stem cells derived from adipose tissue, bone marrow and dental pulp. Journal of Bone and Mineral Metabolism, 33(4), 371–382.
Galler, K. M., et al. (2011). Scaffolds for dental pulp tissue engineering. Advances in Dental Research, 23(3), 333–339.
Qu, T., et al. (2014). Magnesium-containing nanostructured hybrid scaffolds for enhanced dentin regeneration. Tissue Engineering Part A, 20(17–18), 2422–2433.
Wang, J., et al. (2010). The odontogenic differentiation of human dental pulp stem cells on nanofibrous poly(L-lactic acid) scaffolds in vitro and in vivo. Acta Biomaterialia, 6(10), 3856–3863.
Yang, X., et al. (2010). The performance of dental pulp stem cells on nanofibrous PCL/gelatin/nHA scaffolds. Journal of Biomedical Materials Research. Part A, 93(1), 247–257.
Kwon, Y.S., et al. (2015). Behaviour of human dental pulp cells cultured in a collagen hydrogel scaffold crosslinked with cinnamaldehyde. International Endodontic Journal.
Cavalcanti, B. N., Zeitlin, B. D., & Nor, J. E. (2013). A hydrogel scaffold that maintains viability and supports differentiation of dental pulp stem cells. Dental Materials, 29(1), 97–102.
Park, S. J., et al. (2013). Glycol chitin-based thermoresponsive hydrogel scaffold supplemented with enamel matrix derivative promotes odontogenic differentiation of human dental pulp cells. Journal of Endodontics, 39(8), 1001–1007.
Ferroni, L., et al. (2015). A hyaluronan-based scaffold for the in vitro construction of dental pulp-like tissue. International Journal of Molecular Sciences, 16(3), 4666–4681.
Jo, Y. Y., et al. (2007). Isolation and characterization of postnatal stem cells from human dental tissues. Tissue Engineering, 13(4), 767–773.
Gronthos, S., et al. (2002). Stem cell properties of human dental pulp stem cells. Journal of Dental Research, 81(8), 531–535.
Zhang, W., et al. (2006). Multilineage differentiation potential of stem cells derived from human dental pulp after cryopreservation. Tissue Engineering, 12(10), 2813–2823.
Navabazam, A. R., et al. (2013). Characterization of mesenchymal stem cells from human dental pulp, preapical follicle and periodontal ligament. Iran Journal of Reproductive Medicine, 11(3), 235–242.
**ng, J., et al. (2015). AGS3 is involved in TNF-alpha medicated osteogenic differentiation of human dental pulp stem cells. Differentiation, 89(5), 128–136.
Akpinar, G., et al. (2014). Phenotypic and proteomic characteristics of human dental pulp derived mesenchymal stem cells from a natal, an exfoliated deciduous, and an impacted third molar tooth. Stem Cells International, 2014, 457059.
Lei, M., et al. (2014). Mesenchymal stem cell characteristics of dental pulp and periodontal ligament stem cells after in vivo transplantation. Biomaterials, 35(24), 6332–6343.
d’Aquino, R., et al. (2009). Human mandible bone defect repair by the grafting of dental pulp stem/progenitor cells and collagen sponge biocomplexes. European Cells & Materials, 18, 75–83.
Salgado, A. J., et al. (2006). Adult stem cells in bone and cartilage tissue engineering. Current Stem Cell Research & Therapy, 1(3), 345–364.
Kim, B. C., et al. (2012). Osteoblastic/cementoblastic and neural differentiation of dental stem cells and their applications to tissue engineering and regenerative medicine. Tissue Engineering. Part B, Reviews, 18(3), 235–244.
Laino, G., et al. (2005). A new population of human adult dental pulp stem cells: a useful source of living autologous fibrous bone tissue (LAB). Journal of Bone and Mineral Research, 20(8), 1394–1402.
Papaccio, G., et al. (2006). Long-term cryopreservation of dental pulp stem cells (SBP-DPSCs) and their differentiated osteoblasts: a cell source for tissue repair. Journal of Cellular Physiology, 208(2), 319–325.
Bonnamain, V., et al. (2013). Human dental pulp stem cells cultured in serum-free supplemented medium. Frontiers in Physiology, 4, 357.
Kanafi, M. M., et al. (2014). Dental pulp stem cells immobilized in alginate microspheres for applications in bone tissue engineering. International Endodontic Journal, 47(7), 687–697.
Venezia, E., Goldstein, M., & Schwartz Z. The use of enamel matrix derivative in periodontal therapy]. Refuat Hapeh Vehashinayim (1993), 2002. 19(3): p. 19–34, 88.
Hammarstrom, L., Heijl, L., & Gestrelius, S. (1997). Periodontal regeneration in a buccal dehiscence model in monkeys after application of enamel matrix proteins. Journal of Clinical Periodontology, 24(9 Pt 2), 669–677.
Heldin, C. H., & Westermark, B. (1999). Mechanism of action and in vivo role of platelet-derived growth factor. Physiological Reviews, 79(4), 1283–1316.
Lynch, S. E., et al. (1991). The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing. Journal of Periodontology, 62(7), 458–467.
Camilleri, J., & Pitt Ford, T. R. (2006). Mineral trioxide aggregate: a review of the constituents and biological properties of the material. International Endodontic Journal, 39(10), 747–754.
Katsamakis, S., et al. (2013). Histological responses of the periodontium to MTA: a systematic review. Journal of Clinical Periodontology, 40(4), 334–344.
Ajlan, S.A., et al. (2015). Osteogenic differentiation of dental pulp stem cells under the influence of three different materials. BMC Oral Health, 15(1).
Yasui, T., et al. (2015). Purified human dental pulp stem cells promote osteogenic regeneration. Journal of Dental Research.
de Mendonca Costa, A., et al. (2008). Reconstruction of large cranial defects in nonimmunosuppressed experimental design with human dental pulp stem cells. The Journal of Craniofacial Surgery, 19(1), 204–210.
Petridis, X., et al. (2015). Bone regeneration in critical-size calvarial defects using human dental pulp cells in an extracellular matrix-based scaffold. Journal of Cranio-Maxillo-Facial Surgery, 43(4), 483–490.
Kuo, T. F., et al. (2015). An in vivo swine study for xeno-grafts of calcium sulfate-based bone grafts with human dental pulp stem cells (hDPSCs). Materials Science & Engineering, C: Materials for Biological Applications, 50, 19–23.
Kwon, D. Y., et al. (2015). A computer-designed scaffold for bone regeneration within cranial defect using human dental pulp stem cells. Science Reports, 5, 12721.
Wei, X., et al. (2007). Expression of mineralization markers in dental pulp cells. Journal of Endodontics, 33(6), 703–708.
Dai, J., et al. (2012). The effect of co-culturing costal chondrocytes and dental pulp stem cells combined with exogenous FGF9 protein on chondrogenesis and ossification in engineered cartilage. Biomaterials, 33(31), 7699–7711.
Vasandan, A. B., et al. (2014). Functional differences in mesenchymal stromal cells from human dental pulp and periodontal ligament. Journal of Cellular and Molecular Medicine, 18(2), 344–354.
Werle, S.B., et al. (2015). Carious deciduous teeth are a potential source for dental pulp stem cells. Clinical Oral Investigations.
Nemeth, C. L., et al. (2014). Enhanced chondrogenic differentiation of dental pulp stem cells using nanopatterned PEG-GelMA-HA hydrogels. Tissue Engineering Part A, 20(21–22), 2817–2829.
Ibarretxe, G., et al. (2012). Neural crest stem cells from dental tissues: a new hope for dental and neural regeneration. Stem Cells International, 2012, 103503.
Ross, J. J., & Verfaillie, C. M. (2008). Evaluation of neural plasticity in adult stem cells. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 363(1489), 199–205.
Palmer, T. D., et al. (2001). Cell culture. Progenitor cells from human brain after death. Nature, 411(6833), 42–43.
Janebodin, K., et al. (2011). Isolation and characterization of neural crest-derived stem cells from dental pulp of neonatal mice. PloS One, 6(11), e27526.
Sakai, K., et al. (2012). Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms. Journal of Clinical Investigation, 122(1), 80–90.
Nosrat, I. V., et al. (2004). Dental pulp cells provide neurotrophic support for dopaminergic neurons and differentiate into neurons in vitro; implications for tissue engineering and repair in the nervous system. European Journal of Neuroscience, 19(9), 2388–2398.
Govindasamy, V., et al. (2010). Inherent differential propensity of dental pulp stem cells derived from human deciduous and permanent teeth. Journal of Endodontics, 36(9), 1504–1515.
Osathanon, T., Nowwarote, N., & Pavasant, P. (2011). Basic fibroblast growth factor inhibits mineralization but induces neuronal differentiation by human dental pulp stem cells through a FGFR and PLCgamma signaling pathway. Journal of Cellular Biochemistry, 112(7), 1807–1816.
Kiraly, M., et al. (2009). Simultaneous PKC and cAMP activation induces differentiation of human dental pulp stem cells into functionally active neurons. Neurochemistry International, 55(5), 323–332.
Aanismaa, R., et al. (2012). Human dental pulp stem cells differentiate into neural precursors but not into mature functional neurons. Stem Cell Discovery, 02(03), 85–91.
Chang, C. C., et al. (2014). Neurogenic differentiation of dental pulp stem cells to neuron-like cells in dopaminergic and motor neuronal inductive media. Journal of the Formosan Medical Association, 113(12), 956–965.
Feng, X., et al. (2013). Age-dependent impaired neurogenic differentiation capacity of dental stem cell is associated with Wnt/beta-catenin signaling. Cellular and Molecular Neurobiology, 33(8), 1023–1031.
Kanafi, M., et al. (2014). Midbrain cues dictate differentiation of human dental pulp stem cells towards functional dopaminergic neurons. Journal of Cellular Physiology, 229(10), 1369–1377.
Feng, X., et al. (2014). 3D porous chitosan scaffolds suit survival and neural differentiation of dental pulp stem cells. Cellular and Molecular Neurobiology, 34(6), 859–870.
Martens, W., et al. (2014). Human dental pulp stem cells can differentiate into Schwann cells and promote and guide neurite outgrowth in an aligned tissue-engineered collagen construct in vitro. FASEB Journal, 28(4), 1634–1643.
Kumar, A., Bhattacharyya, S., & Rattan, V. (2015). Effect of uncontrolled freezing on biological characteristics of human dental pulp stem cells. Cell Tissue Bank.
Arthur, A., et al. (2008). Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues. Stem Cells, 26(7), 1787–1795.
Arthur, A., et al. (2009). Implanted adult human dental pulp stem cells induce endogenous axon guidance. Stem Cells, 27(9), 2229–2237.
Karaoz, E., et al. (2011). Human dental pulp stem cells demonstrate better neural and epithelial stem cell properties than bone marrow-derived mesenchymal stem cells. Histochemistry and Cell Biology, 136(4), 455–473.
Nesti, C., et al. (2011). Human dental pulp stem cells protect mouse dopaminergic neurons against MPP+ or rotenone. Brain Research, 1367, 94–102.
Dai, J. W., et al. (2013). p75 neurotrophin receptor positive dental pulp stem cells: new hope for patients with neurodegenerative disease and neural injury. Shanghai Kou Qiang Yi Xue, 22(4), 469–472.
Sun, H. H., et al. (2014). Investigation of dental pulp stem cells isolated from discarded human teeth extracted due to aggressive periodontitis. Biomaterials, 35(35), 9459–9472.
Favero, M., et al. (2015). Early knee osteoarthritis. RMD Open, 1(Suppl 1), e000062.
Sharma, L. (2016). Osteoarthritis year in review 2015: clinical. Osteoarthritis and Cartilage, 24(1), 36–48.
Khanna, A., Shin, S., & Rao, M. S. (2008). Stem cells for the treatment of neurological disorders. CNS & Neurological Disorders: Drug Targets, 7(1), 98–109.
Kerkis, I., et al. (2015). Neural and mesenchymal stem cells in animal models of Huntington’s disease: past experiences and future challenges. Stem Cell Research & Therapy, 6, 232.
Yao, Y., et al. (2015). Combined MSC secreted factors and neural stem cell transplantation promote functional recovery of PD rats. Cell Transplantation.
Li, X., et al. (2015). A therapeutic strategy for spinal cord defect: human dental follicle cells combined with aligned PCL/PLGA electrospun material. BioMed Research International, 2015, 197183.
Young, F., Sloan, A., & Song, B. (2013). Dental pulp stem cells and their potential roles in central nervous system regeneration and repair. Journal of Neuroscience Research, 91(11), 1383–1393.
Zhang, R., et al. (2015). Preparation of bionic collagen-heparin sulfate spinal cord scaffold with three-dimensional print technology. Zhongguo **u Fu Chong Jian Wai Ke Za Zhi, 29(8), 1022–1027.
Wust, S., et al. (2014). Tunable hydrogel composite with two-step processing in combination with innovative hardware upgrade for cell-based three-dimensional bioprinting. Acta Biomaterialia, 10(2), 630–640.
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The authors thank Jonathan Garlick and his laboratory members from the Tufts University, School of Dental Medicine.
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Nuti, N., Corallo, C., Chan, B.M.F. et al. Multipotent Differentiation of Human Dental Pulp Stem Cells: a Literature Review. Stem Cell Rev and Rep 12, 511–523 (2016). https://doi.org/10.1007/s12015-016-9661-9
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DOI: https://doi.org/10.1007/s12015-016-9661-9