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TRANSLATIONAL AND CLINICAL RESEARCH

Putative Dental Pulp-Derived Stem/Stromal Cells Promote Proliferation and Differentiation of Endogenous Neural Cells in the Hippocampus of Mice

^aGrace Dental Clinic, Kaohsiung City, Taiwan;
^bDepartment of Oral Pathology, School of Dentistry, Kaohsiung Medical University, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;
^cYerkes National Primate Research Center,
^dDepartment of Human Genetics,
^eGenetics and Molecular Biology Program, and
^fNeuroscience Program, Emory University School of Medicine, Atlanta, Georgia, USA;
^gCenter for Gene Therapy, Tulane University, New Orleans, Louisiana, USA

Key Words. Rhesus monkey • Higher primates • Dental pulp stem/stromal cells • Bone marrow/mesenchymal stem/stromal cells • Cell therapy

Correspondence: Correspondence: Anthony W.S. Chan, D.V.M., Ph.D., Yerkes National Primate Research Center, Rm. 2212 Neuroscience Bldg., 954 Gatewood Rd., N.E., Atlanta, Georgia 30329, USA. Telephone: 404-712-8347; Fax: 404-727-5289; e-mail: achan{at}genetics.emory.edu

Received on April 1, 2008; accepted for publication on July 31, 2008.

First published online in STEM CELLS EXPRESS  August 7, 2008.

Until now, interest in dental pulp stem/stromal cell (DPSC) research has centered on mineralization and tooth repair. Beginning a new paradigm in DPSC research, we grafted undifferentiated, untreated DPSCs into the hippocampus of immune-suppressed mice. The rhesus DPSC (rDPSC) line used was established from the dental pulp of rhesus macaques and found to be similar to human bone marrow/mesenchymal stem cells, which express Nanog, Rex-1, Oct-4, and various cell surface antigens, and have multipotent differentiation capability. Implantation of rDPSCs into the hippocampus of mice stimulated proliferation of endogenous neural cells and resulted in the recruitment of pre-existing Nestin⁺ neural progenitor cells (NPCs) and β-tubulin-III⁺ mature neurons to the site of the graft. Additionally, many cells born during the first 7 days after implantation proliferated, forming NPCs and neurons, and, to a lesser extent, underwent astrogliosis, forming astrocytes and microglia, by 30 days after implantation. Although the DPSC graft itself was short term, it had long-term effects by promoting growth factor signaling. Implantation of DPSCs enhanced the expression of ciliary neurotrophic factor, vascular endothelial growth factor, and fibroblast growth factor for up to 30 days after implantation. In conclusion, grafting rDPSCs promotes proliferation, cell recruitment, and maturation of endogenous stem/progenitor cells by modulating the local microenvironment. Our results suggest that DPSCs have a valuable, unique therapeutic potential, specifically as a stimulator and modulator of the local repair response in the central nervous system. DPSCs would be a preferable cell source for therapy due to the possibility of a "personalized" stem cell, avoiding the problems associated with host immune rejection.

Disclosure of potential conflicts of interest is found at the end of this article.