Dental pulp stem cells: Potential significance in regenerative medicine

Abstract

To date, three types of dental stem cells have been isolated: Dental Pulp Stem Cells (DPSC), Stem Cells From Human Exfoliated Deciduous Teeth (SHED) and Immature Dental Pulp Stem Cells (IDPC). These dental stem cells are considered as mesenchymal stem cells. They reside within the perivascular niche of dental pulp. They are highly proliferative, clonogenic, multipotent and are similar to mesenchymal Bone Marrow Stem Cells (BMSC). Also, they have high plasticity and can be easy isolated. The expressions of the alkaline phosphatase gene, dentin matrix protein 1 and dentinsialophosphoprotein are verified in these cells. Analyses of gene expression patterns indicated several genes which encode extracellular matrix components, cell adhesion molecules, growth factors and transcription regulators, cell signaling, cell communication or cell metabolism. In both conditions, in vivo and in vitro, these cells have the ability to differentiate into odontoblasts, chondrocytes, osteoblasts, adipocytes, neurons, melanocytes, smooth and skeletal muscles and endothelial cells. In vivo, after implantation, they have shown potential to differentiate into dentin but also into tissues like bone, adipose or neural tissue. In general, DPSCs are considered to have antiinflammatory and immunomodulatory abilities. After being grafted into allogenic tissues these cells are ableto induce immunological tolerance. Immunosuppressive effect is shown through the ability to inhibit proliferation of T lymphocytes. Dental pulp stem cells open new perspectives in therapeutic use not only in dentin regeneration, periodontal tissues and skeletoarticular, tissues of craniofacial region but also in treatment of neurotrauma, autoimmune diseases, myocardial infarction, muscular dystrophy and connective tissue damages.Iz zubne pulpe su do danas izolovane tri populacije maticnih celija koje su oznacene kao maticne celije zubne pulpe (engl. Dental Pulp Stem Cells, DPSC), maticne celije iz eksfoliranih mlecnih zuba (engl. Stem Cells From Human Exfoliated Decidual Teeth, SHED) i nezrele maticne celije zubne pulpe (engl. Immature Dental Pulp Stem Cells, IDPC). Sve maticne celije zubne pulpe su ektomezenhimalnog porekla i lokalizovane su u perivaskularnoj nisi. One se lako i efikasno izoluju, visoko su proliferativne, klonogene, multipotentne, ispoljavaju visok stepen plasticiteta i i slicne su mezenhimalnim maticnim celijama kostane srzi (BMSC). U njima je pokazana visoka ekspresija gena alkalne fosfataze, proteina 1 matriksa dentina i dentin-sijalofosfoproteina. Takodje, istaknuta je vaznost u ovim celijama ekspresije vise gena koji kodiraju sintezu komponenti ekstracelularnog matriksa, molekula celijske adhezije, faktora rasta, transkripcionih faktora, gena prenosa celijskih signala, celijske komunikacije i metabolizma. U uslovima in vitro ili in vivo ove celije mogu da se diferenciraju, s odredjenim medjusobnim razlikama, u pravcu odontoblasta, hondrocita, osteoblasta, adipocita, neurona/glije, glatkih i skeletnih misicnih celija, endotelnih celija i melanocita. U uslovima in vivo, nakon implantacije, pokazuju razlicit potencijal za formiranje dentina, ali i kostanog, masnog i nervnog tkiva. Generalno se smatra da DPSC imaju anti-inflamatorno dejstvo i ispoljavaju imunom-odulatorni efekat. Takodje, dovode do imunoloske tolerancije ukoliko se implantiraju u alogena tkiva. Sposobnost inhibicije proliferacije T limfocita ukazuje na njihovo imunosupresivno dejstvo. Maticne celije zubne pulpe otvorile su nove perspektive u terapijskoj primeni ovih celija ne samo u regeneraciji dentina, tkiva periodoncijuma i kostano-zglobnog tkiva kraniofacijalne regije, vec i u lecenju neurotraume, autoimunskih oboljenja, infarkta miokarda, misicne distrofije i ostecenja vezivnog tkiva.