Mund-, Kiefer- und Gesichtschirurgie

, Volume 11, Issue 5, pp 259–266 | Cite as

The state of the art in human dental stem cell research

  • Christian Morsczeck
  • Torsten Eugen Reichert
  • Florian Völlner
  • Till Gerlach
  • Oliver Driemel
Übersichtsarbeit

Abstract

This review article arranges the current results of stem cell biology for their use in dentistry. There are different types of stem cells, which are applicable for dental treatments. The use of embryonic stem cells, whose possibilities for breeding an artificial tooth were hardly evaluated, is however ethically precarious. On the other side the ethically harmless adult stem cells, which were isolated for example from bone marrow, were little examined for their capability of differentiation into dental tissues. Therefore their forthcoming use in dentistry is rather improbable. However, dental ectomesenchymal stem cells are more promising for dentistry in future. For example dental pulp stem cells (DPSCs) are capable to differentiate into dentin under in vitro conditions. Moreover it is possible to use periodontal ligament (PDL) stem cells and dental follicle precursors for periodontal tissue differentiations in vitro. Recently new populations of stem cells were isolated from the dental pulp and the PDL. These cells distinguish from the initially isolated DPSCs and PDL stem cells in growth and cell differentiation. Therefore stem cell markers are very important for the characterization of dental stem cells. A significant marker for dental stem cells is STRO-1, which is also a marker for bone marrow derived mesenchymal stem cells. Nonetheless dental stem cells are CD45 negative and they express rarely hematopoietic stem cell markers.

These research results plead for the participation of dental stem cells in dental practice in future.

Keywords

Stem cell biology Dental ectomesenchymal stem cells Differentiation Stem cell markers 

Stand der humanen dentalen Stammzellforschung

Zusammenfassung

Der vorliegende Übersichtsartikel stellt die aktuellen Ergebnisse der Stammzellbiologie unter besonderer Berücksichtigung des Einsatzes von Stammzellen in der Zahnmedizin zusammen. Hierbei sind unterschiedliche Typen von Stammzellen bekannt, deren Verwendung in der Zahnmedizin diskutiert wird. Eine mögliche Quelle sind embryonale Stammzellen, deren Anwendung allerdings ethisch bedenklich und deren Potenzial für die Züchtung eines künstlichen Zahns bis heute nur vereinzelt evaluiert worden ist. Auf der anderen Seite sind die ethisch unbedenklichen adulten Stammzellen, die z. B. aus dem Knochenmark stammen, für Differenzierungen zu Dentalgewebe wenig untersucht wurden, weshalb ihre baldige Nutzung für die Zahnmedizin eher unwahrscheinlich ist. Bessere Aussichten für zukünftige Anwendungen scheinen dentale, ektomesenchymale Stammzellen zu haben. So konnte man z. B. mit dentalen Pulpa-Stammzellen (dental pulp stem cells, DPSCs) Dentin in vitro züchten. Des Weiteren ist es möglich, periodontale Ligament-Stammzellen (PDL) und dentale Follikel Vorläuferzellen (DFV) in vitro in Periodontalgewebe zu differenzieren. In der letzten Zeit wurden neue Stammzellpopulationen aus dem PDL und der Zahn-Pulpa isoliert. Diese Zellen unterscheiden sich im Wachstum und im Differenzierungspotenzial von den primär isolierten DPSCs und PDL-Stammzellen. Bei der genaueren Charakterisierung der unterschiedlichen Stammzellen sind Stammzellmarker hilfreich. Einen sehr guten dentalen Stammzellmarker bietet STRO-1, der auch von mesenchymalen Stammzellen des Knochenmarks exprimiert wird. Darüber hinaus sind die meisten dentalen Stammzellen CD45-negativ und exprimieren sehr selten hämatopoetische Stammzellmarker.

Die aktuellen Forschungsergebnisse lassen einen baldigen Einsatz von dentalen Stammzellen in der Praxis erwarten.

Schlüsselwörter

Stammzellbiologie Dentale ektomesenchymale Stammzellen Differenzierung Stammzellmarker 

Literatur

  1. 1.
    Cowan CA, Klimanskaya I, McMahon J, Atienza J, Witmyer J, Zucker JP, Wang S, Morton CC, McMahon AP, Powers D, Melton DA (2004) Derivation of embryonic stem-cell lines from human blastocysts. N Engl J Med 350:1353–1356PubMedCrossRefGoogle Scholar
  2. 2.
    Crain BJ, Tran SD, Mezey E (2005) Transplanted human bone marrow cells generate new brain cells. J Neurol Sci 233(1–2):121–123PubMedCrossRefGoogle Scholar
  3. 3.
    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 Mar 9; [Epub ahead of print]Google Scholar
  4. 4.
    Gronthos S, Mankani M, Brahim J, Robey PG, Shi S (2000) Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A 97:13625–13630PubMedCrossRefGoogle Scholar
  5. 5.
    Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, DenBesten P, Robey PG, Shi S (2002) Stem cell properties of human dental pulp stem cells. J Dent Res 81:531–535PubMedCrossRefGoogle Scholar
  6. 6.
    Gronthos S, Mrozik K, Shi S, Bartold PM (2006) Ovine periodontal ligament stem cells: isolation, characterization, and differentiation potential. Calcif Tissue Int 79:310–317PubMedCrossRefGoogle Scholar
  7. 7.
    Hakki SS, Berry JE, Somerman MJ (2001) The effect of enamel matrix protein derivative on follicle cells in vitro. J Periodontol 72:679–687PubMedCrossRefGoogle Scholar
  8. 8.
    Handa K, Saito M, Yamauchi M, Kiyono T, Sato S, Teranaka T, Sampath Narayanan A (2002) Cementum matrix formation in vivo by cultured dental follicle cells. Bone 31:606–611PubMedCrossRefGoogle Scholar
  9. 9.
    Harada H, Kettunen P, Jung HS, Mustonenm T, Wang YA, Thesleff I (1999) Localization of putative stem cells in dental epithelium and their association with Notch and FGF signalling. J Cell Biol 147:105–120PubMedCrossRefGoogle Scholar
  10. 10.
    Harada H, Toyono T, Toyoshima K, Yamasaki M, Itoh N, Kato S, Sekine K, Ohuchi H (2002) FGF10 maintains stem cell compartment in developing mouse incisors. Development 129:1533–1541PubMedGoogle Scholar
  11. 11.
    Harada H, Ichimori Y, Yokohama-Tamaki T, Ohshima H, Kawano S, Katsube K, Wakisaka S (2006) Stratum intermedium lineage diverges from ameloblast lineage via Notch signalling. Biochem Biophys Res Commun 340:611–616PubMedCrossRefGoogle Scholar
  12. 12.
    Hassan MQ, Tare RS, Lee SH, Mandeville M, Morasso MI, Javed A, van Wijnen AJ, Stein JL, Stein GS, Lian JB (2006) BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network. J Biol Chem 281:40515–40526PubMedCrossRefGoogle Scholar
  13. 13.
    Huttmann A, Li CL, Duhrsen U (2003) Bone marrow-derived stem cells and “plasticity”. Ann Hematol 82:599–604PubMedCrossRefGoogle Scholar
  14. 14.
    Iohara K, Zheng L, Ito M, Tomokiyo A, Matsushita K, Nakashima M (2006) Side population cells isolated from porcine dental pulp tissue with self-renewal and multipotency for dentinogenesis, chondrogenesis, adipogenesis, and neurogenesis. Stem Cells 24:2493–2503PubMedCrossRefGoogle Scholar
  15. 15.
    Kawanabe N, Murakami K, Takano-Yamamoto T (2006) The presence of ABCG2-dependent side population cells in human periodontal ligaments. Biochem Biophys Res Commun. 344:1278–1283PubMedCrossRefGoogle Scholar
  16. 16.
    Kemoun 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 Apr 19; [Epub ahead of print]Google Scholar
  17. 17.
    Kerkis I, Kerkis A, Dozortsev D, Stukart-Parsons GC, 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 184:105–116PubMedCrossRefGoogle Scholar
  18. 18.
    Luan X, Ito Y, Dangaria S, Diekwisch TG (2006) Dental follicle progenitor cell heterogeneity in the developing mouse periodontium. Stem Cells Dev 15:595–608PubMedCrossRefGoogle Scholar
  19. 19.
    Maria OM, Khosravi R, Mezey E, Tran SD (2007) Cells from bone marrow that evolve into oral tissues and their clinical applications. Oral Dis 13:11–16PubMedCrossRefGoogle Scholar
  20. 20.
    Mezey E, Chandross KJ, Hartam G, Maki RA, McKercher SR (2000) Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290:1779–1782PubMedCrossRefGoogle Scholar
  21. 21.
    Mezey E, Key S, Vogelsang G, Szalayova I, Lange GD, Crain B (2003) Transplanted bone marrow generates new neurons in human brains. Proc Natl Acad Sci U S A 100:1364–1369PubMedCrossRefGoogle Scholar
  22. 22.
    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 100:5807–5812PubMedCrossRefGoogle Scholar
  23. 23.
    Modino SA, Sharpe PT (2005) Tissue engineering of teeth using adult stem cells. Arch Oral Biol 50:255–258PubMedCrossRefGoogle Scholar
  24. 24.
    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 24:155–165PubMedCrossRefGoogle Scholar
  25. 25.
    Morsczeck C, Moehl C, Gotz W, Heredia A, Schaffer TE, Eckstein N, Sippel C, Hoffmann KH (2005) In vitro differentiation of human dental follicle cells with dexamethasone and insulin. Cell Biol Int 29:567–575PubMedCrossRefGoogle Scholar
  26. 26.
    Morsczeck C (2006) Gene expression of runx2, osterix, c-fos, DLX-3, DLX-5 & MSX-2 in dental follicle cells during osteogenic differentiation in vitro. Calcif Tissue Int 78:98–102PubMedCrossRefGoogle Scholar
  27. 27.
    Ohazama A, Modino SA, Miletich I, Sharpe PT (2004) Stem-cell-based tissue engineering of murine teeth. J Dent Res 83(7):518–522PubMedGoogle Scholar
  28. 28.
    Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147PubMedCrossRefGoogle Scholar
  29. 29.
    Popowics T, Foster BL, Swanson EC, Fong H, Somerman MJ (2005) Defining the roots of cementum formation .Cells Tissues Organs 181:248–257CrossRefGoogle Scholar
  30. 30.
    Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, Young M, Robey PG, Wang CY, Shi S (2004) Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364:149–155PubMedCrossRefGoogle Scholar
  31. 31.
    Shi S, Robey PG, Gronthos S (2001) Comparison of human dental pulp and bone marrow stromal stem cells by cDNA microarray analysis. Bone 29:532–539PubMedCrossRefGoogle Scholar
  32. 32.
    Shi S, Gronthos S (2003) Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone Miner Res 18:696–704PubMedCrossRefGoogle Scholar
  33. 33.
    Simmons PJ, Torok-Storb B (1991) Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood 78:55–62PubMedGoogle Scholar
  34. 34.
    Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, Liu H, Gronthos S, Wang CY, Shi S, Wang S (2006) Mesenchymal stem cell-mediated functional tooth regeneration in Swine. PLoS ONE Dec 20;1:e79Google Scholar
  35. 35.
    Terskikh AV, Bryant PJ, Schwartz PH (2006) Mammalian stem cells. Pediatr Res 59:13R–20RPubMedCrossRefGoogle Scholar
  36. 36.
    Tomita M, Mori T, Maruyama K, Zahir T, Ward M, Umezawa A, Young MJ (2006) A comparison of neural differentiation and retinal transplantation with bone marrow-derived cells and retinal progenitor cells. Stem Cells 24:2270–2278PubMedCrossRefGoogle Scholar
  37. 37.
    Trounson A (2004) Stem cells, plasticity and cancer – uncomfortable bed fellows. Development 131:2763–2768PubMedCrossRefGoogle Scholar
  38. 38.
    Woodbury D, Schwarz EJ, Prockop DJ, and Black IB (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61:364–370PubMedCrossRefGoogle Scholar
  39. 39.
    Yen AH, Sharpe PT (2006) Regeneration of teeth using stem cell-based tissue engineering. Expert Opin Biol Ther. 6:9–16PubMedCrossRefGoogle Scholar
  40. 40.
    Yoshimura Y (2006) Bioethical aspects of regenerative and reproductive medicine. Hum Cell 19:83–86PubMedCrossRefGoogle Scholar
  41. 41.
    Yoshizawa T, Takizawa F, Iizawa F, Ishibashi O, Kawashima H, Matsuda A, Endo N, Kawashima H (2004) Homeobox protein MSX2 acts as a molecular defense mechanism for preventing ossification in ligament fibroblasts. Mol Cell Biol 24:3460–3472PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Christian Morsczeck
    • 1
  • Torsten Eugen Reichert
    • 2
  • Florian Völlner
    • 1
  • Till Gerlach
    • 2
  • Oliver Driemel
    • 2
  1. 1.Institut für HumangenetikUniversität RegensburgRegensburgGermany
  2. 2.Klinik und Poliklinik für Mund-, Kiefer- und GesichtschirurgieUniversität RegensburgRegensburgGermany

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