Science behind Dental Pulp Stem Cells

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Science behind Dental Pulp Stem Cells
The dental pulp has long been recognized as a source of adult stem cells. There are approximately 374 relevant publications on stem cells in dental pulp.
Stem cells in dental pulp

There are many publications describing and characterizing the stem cells found in dental pulp. Below are a few representative samples.

Renard E, Lopez-Cazaux S, Guicheux J, Weiss P, Laboux O, Alliot-Licht B.

Stem cells of dental pulp.

C R Biol. 2007 Sep;330(9):635-43. Epub 2007 Aug 13. French.

PMID: 17720580
Jo YY, Lee HJ, Kook SY, Choung HW, Park JY, Chung JH, Choung YH, Kim ES, Yang HC, Choung PH.

Isolation and characterization of postnatal stem cells from human dental tissues.

Tissue Eng. 2007 Apr;13(4):767-73.

PMID: 17432951
Kerkis I, Kerkis A, Dozortsev D, Stukart-Parsons GC, Gomes Massironi SM, Pereira LV, Caplan AI, Cerruti HF.

Isolation and characterization of a population of immature dental pulp stem cells expressing OCT-4 and other embryonic stem cell markers.

Cells Tissues Organs. 2006;184(3-4):105-16.

PMID: 17409736
Gronthos S, Mankani M, Brahim J, Robey PG, Shi S.

Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo.

Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13625-30.

PMID: 11087820

Stem cells in primary teeth

Osteoblasts, chondracytes, adipocytes, and Mesenchymal stem cells were first identified in primary teeth in 2003. In this publication, the cells were identified by a differentiation assay as well as cell surface marker characterization. This publication also describes the unusually fast proliferation rate and high population doublings of these cells which could make them a good candidate for therapeutic use. These results have been confirmed by other labs since this original publication.

Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, Shi S.

SHED: stem cells from human exfoliated deciduous teeth.

Proc Natl Acad Sci U S A. 2003 May 13;100(10):5807-12. Epub 2003 Apr 25.

PMID: 12716973
Functionality after cryopreservation

The research community has only recently been trying to answer this question as a result there is not a huge amount of direct data. We do not have a clear understanding of how long these cells retain their therapeutic potential during cryopreservation however we have every reason to believe that it will be at least as long as the life span of the donor. Below are a few references for this belief.

References for storage

  1. This reference is a general reference for the storage of cells and not specifically stem cells by the American Type Culture Collection (ATCC).  ATCC is one of the premier suppliers of cells for research in the United States.

How long can frozen cells be kept in liquid nitrogen or dry ice without affecting recovery?
Answer: Cells that are properly frozen using an effective cryoprotective agent can be stored in liquid nitrogen indefinitely without affecting recovery. Cells of CCL-1 were cryopreserved in February 1962. After decades in liquid nitrogen or its vapor, their viability has not significantly declined.

  1. This particular reference states that stem cells from cord blood is expected to last more than 50 years.

Q: How long can cord blood be preserved?

A: The first transplanted cord blood occurred in 1988. Because cord blood research is so new, further studies are ongoing. It is believed that because stem cells have much the same properties as sperm cells, their viability would be similar: greater than fifty years.

  1. The discovery of useful cells in teeth is a relatively new discovery and therefore long term studies are still being conducted.  This reference states that cells from teeth have successfully been stored for 2 years without any measurable loss of functionality.  They did not conduct longer studies in this experiment.

Papaccio G, Graziano A, d'Aquino R, Graziano MF, Pirozzi G, Menditti D, De Rosa A, Carinci F, Laino G.

Long-term cryopreservation of dental pulp stem cells (SBP-DPSCs) and their differentiated osteoblasts: a cell source for tissue repair.

J Cell Physiol. 2006 Aug;208(2):319-25. PMID: 16622855
These studies found similar results. The first study specifically used SHED cells.

Zhang W, Walboomers XF, Shi S, Fan M, Jansen JA.

Multilineage differentiation potential of stem cells derived from human dental pulp after cryopreservation.

Tissue Eng. 2006 Oct;12(10):2813-23.

PMID: 17518650
Seo BM, Miura M, Sonoyama W, Coppe C, Stanyon R, Shi S.

Recovery of stem cells from cryopreserved periodontal ligament.

J Dent Res. 2005 Oct;84(10):907-12.

PMID: 16183789

BioEDEN, has successfully tested for the expression of STRO1 mesenchymal stem cell marker on samples that have been cryopreserved for 1 year and we intend to routinely test for this expression in the future. Dr. Shi verbally stated that his lab has successfully conducted differentiation assays on SHED cells that were cryopreserved for 18 months and that they had never had a failure of the cells to be functional after thaw. (Verbal conversation with Mike Byrom in 2005).

Applications of Dental Pulp Stem Cells.

All of the studies listed below were conducted using dental pulp stem cells.

Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, Liu H, Gronthos S, Wang CY, Shi S, Wang S.

Mesenchymal stem cell-mediated functional tooth regeneration in swine.

PLoS ONE. 2006 Dec 20;1:e79.

PMID: 17183711
In this study, they grew teeth in vitro and implanted them into mice.

Nakao K, Morita R, Saji Y, Ishida K, Tomita Y, Ogawa M, Saitoh M, Tomooka Y, Tsuji T.

The development of a bioengineered organ germ method.

Nat Methods. 2007 Mar;4(3):227-30. Epub 2007 Feb 18.

PMID: 17322892

Fang D, Seo BM, Liu Y, Sonoyama W, Yamaza T, Zhang C, Wang S, Shi S.

Transplantation of mesenchymal stem cells is an optimal approach for plastic surgery.

Stem Cells. 2007 Apr;25(4):1021-8. Epub 2006 Dec 14.

PMID: 17170063

  • Bone Growth

Otaki S, Ueshima S, Shiraishi K, Sugiyama K, Hamada S, Yorimoto M, Matsuo O.

Mesenchymal progenitor cells in adult human dental pulp and their ability to form bone when transplanted into immunocompromised mice.

Cell Biol Int. 2007 Oct;31(10):1191-7. Epub 2007 Apr 14.

PMID: 17524678
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.

In vitro bone production using stem cells derived from human dental pulp.

J Craniofac Surg. 2006 May;17(3):511-5.

PMID: 16770190
Laino G, d'Aquino R, Graziano A, Lanza V, Carinci F, Naro F, Pirozzi G, Papaccio G.

A new population of human adult dental pulp stem cells: a useful source of living autologous fibrous bone tissue (LAB).
J Bone Miner Res. 2005 Aug;20(8):1394-402. Epub 2005 Mar 28.
PMID: 16007337

Shi S, Bartold PM, Miura M, Seo BM, Robey PG, Gronthos S.

The efficacy of mesenchymal stem cells to regenerate and repair dental structures.

Orthod Craniofac Res. 2005 Aug;8(3):191-9. Review.

PMID: 16022721
Applications of Adipocytes and Mesenchymal Stem Cells from other sources

There has been significant work to better characterize and compare the cells found in teeth with the same type of cells from other sources, that have proven therapeutic usefulness. The current research indicates that the Mesenchymal stem cells found in teeth are as therapeutically useful as the MSC’s found in bone marrow or peripheral blood.

Yamada Y, Fujimoto A, Ito A, Yoshimi R, Ueda M.

Cluster analysis and gene expression profiles: a cDNA microarray system-based comparison between human dental pulp stem cells (hDPSCs) and human mesenchymal stem cells (hMSCs) for tissue engineering cell therapy.

Biomaterials. 2006 Jul;27(20):3766-81. Epub 2006 Mar 24.

PMID: 16563496
Shi S, Robey PG, Gronthos S.

Comparison of human dental pulp and bone marrow stromal stem cells by cDNA microarray analysis.
Bone. 2001 Dec;29(6):532-9.
PMID: 11728923

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