Dental Pulp Stem Cell Heterogeneity: Finding Superior Quality “Needles” in a Dental Pulpal “Haystack” for Regenerative Medicine-Based Applications

Abstract

Human dental pulp stem/stromal cells (hDPSCs) derived from the permanent secondary dentition are recognised to possess certain advantageous traits, which support their potential use as a viable source of mesenchymal stem/stromal cells (MSCs) for regenerative medicine-based applications. However, the well-established heterogeneous nature of hDPSC subpopulations, coupled with their limited numbers within dental pulp tissues, has impeded our understanding of hDPSC biology and the translation of sufficient quantities of these cells from laboratory research, through successful therapy development and clinical applications. This article reviews our current understanding of hDPSC biology and the evidence underpinning the molecular basis of their heterogeneity, which may be exploited to distinguish individual subpopulations with specific or superior characteristics for regenerative medicine applications. Pertinent unanswered questions which still remain, regarding the developmental origins, hierarchical organisation, and stem cell niche locations of hDPSC subpopulations and their roles in hDPSC heterogeneity and functions, will further be explored. Ultimately, a greater understanding of how key features, such as specific cell surface, senescence and other relevant genes, and protein and metabolic markers, delineate between hDPSC subpopulations with contrasting stemness, proliferative, multipotency, immunomodulatory, anti-inflammatory, and other relevant properties is required. Such knowledge advancements will undoubtedly lead to the development of novel screening, isolation, and purification strategies, permitting the routine and effective identification, enrichment, and expansion of more desirable hDPSC subpopulations for regenerative medicine-based applications. Furthermore, such innovative measures could lead to improved cell expansion, manufacture, and banking procedures, thereby supporting the translational development of hDPSC-based therapies in the future.

An Overview of the Use of Medicinal Plants in Regenerative Dentistry

“…This feature confers them vast differentiation potential, in addition to their ability to secrete trophic factors and their immunoregulatory properties. DPSCs can differentiate into odontoblasts, osteocytes/osteoblasts, adipocytes, chondrocytes, or neural cells [6] [7].…”

“…During tooth development, primitive ectomesenchyme becomes enclosed within the prospective teeth to form the dental pulp, a rich source of stem cells. Odontogenesis (the process of tooth development) involves the cell matrix of types and specific cellular processes which result in the differentiation, growth, maturation and eruption of developing teeth in the mouth [5] [6].…”

Hopes and opportunities of stem cells from human exfoliated deciduous teeth (SHED) in cartilage tissue regeneration

“…Other advantages of SHED include painless cell collection and minimal risk of invasion ( Kawashima, 2012 ; Fernandes et al, 2020 ). More importantly, SHED and DPSC have been shown to differentiate into mesodermal ( Ishkitiev et al, 2010 ; Nourbakhsh et al, 2011 ; Gugliandolo and Mazzon, 2022 ; Kok et al, 2022 ), ectodermal, and endodermal lineage ( Ishkitiev et al, 2010 ; Gugliandolo and Mazzon, 2022 ; Kok et al, 2022 ) ( Figure 1 ). Despite the very high morphological similarity of deciduous cells to DPSCs, studies suggest that SHED has higher rates of differentiation and proliferation than DPSC ( Nakamura et al, 2009 ; Wang et al, 2012 ).…”

Osteogenic differentiation capacity of dental pulp stem cells on 3D printed polyurethane/boric acid scaffold

“…Dental pulp tissue, a unique source of mesenchymal stem cells (MSCs), shows similar characteristics with human bone marrow derived MSCs. Dental pulp stem cells (DPSCs) are derived from migrating neural crest cells and they have differentiation ability into odontoblasts which forms mineralized matrix of dentin as well as multilineage differentiation capacities (e.g., dentinogenic, osteogenic, neurogenic) [11,12]. PUs as segmented block copolymers have a combination of excellent mechanical, physical and chemical properties, and exceptional biocompatibility.…”