First published online May 22, 2008
Adult Human Dental Pulp Stem Cells Differentiate Towards Functionally
Active Neurons Under Appropriate Environmental Cues
Abstract
Human adult dental pulp stem cells (DPSC) reside within the
perivascular niche of dental pulp and are thought to originate from
migrating cranial neural crest (CNC) cells. During embryonic
development, CNC cells differentiate into a wide variety of cell
types including neurons of the peripheral nervous system. Previously,
we have demonstrated that DPSC derived from adult human third molar
teeth differentiate into cell types reminiscent of CNC embryonic
ontology. We hypothesized that DPSC exposed to the appropriate
environmental cues would differentiate into functionally active
neurons. The data demonstrated that ex vivo expanded human adult DPSC
responded to neuronal inductive conditions both in vitro and in vivo.
Human adult DPSC, but not human foreskin fibroblasts (HFF) acquired a
neuronal morphology, and expressed neuronal specific markers at both
the gene and protein levels. Culture expanded DPSC also exhibited the
capacity to produce a sodium current consistent with functional
neuronal cells when exposed to neuronal inductive media. Furthermore,
the response of human DPSC and HFF to endogenous neuronal
environmental cues was determined in vivo using an avian xeno-
transplantation assay. DPSC expressed neuronal markers and acquired a
neuronal morphology following transplantation into the mesencephalon
of embryonic day two chicken embryo, while HFF maintained a thin
spindle fibroblastic morphology. We propose that adult human DPSC
provide a readily accessible source of exogenous stem/precursor cells
which have the potential for use in cell therapeutic paradigms to
treat neurological disease.
____________
Agnes Arthur 1, Grigori Rychkov 2, Songtao Shi 3, Simon Andrea Koblar
4, Stan Gronthos 5*
1 The Australian Research Council, Centre for the Molecular Genetics
of Development, University of Adelaide, Adelaide, 5005, SA,
Australia.; School of Molecular and Biomedical Science (Genetics),
University of Adelaide, Adelaide, 5005, SA, Australia.; Mesenchymal
Stem Cell Group, Division of Haematology, Institute of Medical and
Veterinary Science, Hanson Institute/Adelaide University, Adelaide,
5000, SA, Australia.
2 School of Molecular and Biomedical Science (Physiology)
of Adelaide, Adelaide, 5005, SA, Australia.
3 School of Dentistry, University of Southern California, Los
Angeles, 90089-0641, CA, USA.
4 The Australian Research Council, Centre for the Molecular Genetics
of Development, University of Adelaide, Adelaide, 5005, SA,
Australia.; School of Molecular and Biomedical Science (Genetics),
University of Adelaide, Adelaide, 5005, SA, Australia.
5 Mesenchymal Stem Cell Group, Division of Haematology, Institute of
Medical and Veterinary Science, Hanson Institute/Adelaide University,
Adelaide, 5000, SA, Australia.
* To whom correspondence should be addressed. E-mail:
stan.gronthos@
________
Author Contributions: A.A.: Conception and design, collection and/or
assembly of data, data analysis and interpretation, manuscript
writing.; G.R.: Collection and/or assembly of data, data analysis and
interpretation, manuscript writing.; S.S.: Conception and design,
provision of study material or patients.; S.K.: Conception and
design, data analysis and interpretation, manuscript writing,
financial support, final approval of manuscript.; S.G.: Conception
and design, data analysis and interpretation, manuscript writing,
financial support, final approval of manuscript.
S.A. Koblar and S. Gronthos contributed equally to this work.
Key Words. Dental Pup Stem Cells (DPSC), neuronal differentiation
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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