Dental Pulp-Derived Mesenchymal Stem Cells for Modeling Genetic Disorders

Abstract

A subpopulation of mesenchymal stem cells, developmentally derived from multipotent neural crest cells that form multiple facial tissues, resides within the dental pulp of human teeth. These stem cells show high proliferative capacity in vitro and are multipotent, including adipogenic, myogenic, osteogenic, chondrogenic, and neurogenic potential. Teeth containing viable cells are harvested via minimally invasive procedures, based on various clinical diagnoses, but then usually discarded as medical waste, indicating the relatively low ethical considerations to reuse these cells for medical applications. Previous studies have demonstrated that stem cells derived from healthy subjects are an excellent source for cell-based medicine, tissue regeneration, and bioengineering. Furthermore, stem cells donated by patients affected by genetic disorders can serve as in vitro models of disease-specific genetic variants, indicating additional applications of these stem cells with high plasticity. This review discusses the benefits, limitations, and perspectives of patient-derived dental pulp stem cells as alternatives that may complement other excellent, yet incomplete stem cell models, such as induced pluripotent stem cells, together with our recent data.

The chromatin accessibility landscape in the dental pulp of mouse molars and incisors

“…Specifically, bivalent chromatin domains are formed at developmental genes that are poised for rapid activation. MSCs of dental pulp originate from the neural crest cells, a transient multipotent cell population derived from the dorsal neural tube (Masuda et al, 2021). Distinct TFs control neural crest differentiation during craniofacial and dental development (Prasad et al, 2019;Balic & Thesleff, 2015).…”

“…Over the past few years, dental pulp-derived mesenchymal stem cells (MSCs) have emerged as strong candidates for tissue engineering and regenerative medicine (Masuda et al, 2021;Augustine et al, 2021;Gan et al, 2020;Bonaventura et al, 2020). MSCs are capable of differentiating into multiple lineages such as osteogenic, angiogenic, myogenic, and chondrogenic cells (Nagata et al, 2021;Luo et al, 2018;Potdar et al, 2015).…”

The Role of Epigenetic in Dental and Oral Regenerative Medicine by Different Types of Dental Stem Cells: A Comprehensive Overview

“…Some stem cells share similar characteristics among tissues (adipose tissue, liver, and existing blood in the cord). In addition, they have been discovered in the follicle of the newly formed dental embryo and the root apex of growing permanent teeth, in addition to the periodontal ligament and the pulp of permanent and mature deciduous teeth [ 16 ]. DSCs have been isolated from various alternative sources of human dental tissues, such as stem cells from apical papilla (SCAPs), human exfoliated deciduous teeth (SHEDs), periodontal ligament stem cells (PDLSCs), and dental follicle precursor cells (DFPCs).…”

“…Stem cells originate from the dental pulp of permanent teeth, which contains wisdom teeth surgically removed that do not contribute to the occlusion of permanent teeth. Genetic and congenital disorders are often characterized by defects in the fetal or postnatal stages [ 16 ].…”

“…However, several differences were observed at the molecular and cellular levels. Rodent nerve injury models showed that these transplanted cells inhibited apoptosis and inflammation that interfered with repairment while differentiated into oligodendrocytes, which are mature, to stimulate neuroregeneration [ 16 ]. Reduction expression of STRO-1 and regulation of transcription factors, NANOG, OCT4, and nestin, was observed with an upregulation in gingival-derived mesenchymal stem cell (GMSC) passage by Ranga Rao and Subbarayan [ 36 ].…”