Dental tissues as adult stem cell source

Abstract

Multipotent stem cells are the most crucial factor in tissue engineered regeneration procedures. Although bone marrow has been most widely studied and used as mesenchymal stem cell (MSC) source, several attempts have recently been made to obtain multipotential stem cells from more easily accessible sources, including skin, fat, periosteum and dental tissues1-5. In previous studies, skin has been shown as an excellent adult stem cell source, which differentiated into osteogenic and neural cells in vitro and enhanced bone formation in the maxillary sinus floor and nerve regeneration in vivo5,6. Further, stem cells derived from fetus differentiated into primordial germ cell and oocyte, and exhibited similar characteristics compared to embryonic stem cells7,8. However, harvesting skin tissue also involves an invasive procedure, and stem cells from the skin of older donors possess less stemness and regenerative potential than that of younger donors4,5. Dental tissues from extracted teeth could be used as alternative sources of adult stem cells. Dental stem cells were firstly isolated from the pulp tissues of removed third molars (dental pulp stem cell, DPSC), and showed similar characteristics with bone marrow derived MSC1,2. After then, some researchers have succeeded in the isolation of stem cells from the pulp tissues of human exfoliated deciduous teeth (SHED)9 or mesiodens10. Subsequently, other dental tissues, such as periodontal ligament11, root apical papilla12, and tooth follicle13, have been explored as adult stem cell sources. MSC-like characteristics of dental stem cells with plastic adherent growth and colony formation, expression of MSC-specific cell surface markers, and multilineage in vitro differentiation ability were similar to those of MSCs from skin or bone marrow14. However, interestingly, different dental tissues from same donor showed varying stem cell characteristics, including transcription factor expression levels and in vitro differentiation potential15. Stem cells from root papilla showed the highest expression level of transcription factors and cell surface markers15. However, dental follicle derived cells showed enhanced osteoblast-specific genes and ectopic bone formation after in vivo transplantation14, indicating dental follicle is the powerful stem cell source in bone tissue regeneration. Dental pulp is expected to harbor the pools of undifferentiated precursor cells for nerve or vascular tissue regeneration. The most powerful advantage of dental tissues as stem cells source is that primitive and multipotent tissues could be obtained around age 20, a later age compared to that of other stem cell sources, such as umbilical cord blood or matrix. If these dental tissues are preserved for long time without losing their stemness, they could be used as autologous stem cell source for demanding applications in regenerative medicine. A recent study reported the successful isolation of stem cells from long-term cryopreserved dental pulp tissues of deciduous teeth using a cryoprotectant, 90% fetal bovine serum (FBS) and 10% dimethyl sulfoxide16. However, FBS is xenogenic material for human tissue and cells and may alter tissue's properties, and not suitable for long-term preservation of human tissues. Interestingly, an efficient and safe dental tissue cryopreservation method using sucrose and ethylene glycol has been developed, and further analyses are being proceeded for its clinical application (data not published). In near future, the dental tissues, follicle, pulp and root papilla, of extracted wisdom teeth could be cryopreserved for later use as autologous stem cells sources.