Current Stem Cell Research & Therapy - Volume 10, Issue 5, 2015

Stem cell-based therapies are considered as a promising treatment for many clinical usage such as tooth regeneration, bone repairation, spinal cord injury, and so on. However, the ideal stem cell for stem cell-based therapy still remains to be elucidated. In the past decades, several types of stem cells have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs) and stem cells from apical papilla (SCAP), which may be a good source for stem cell-based therapy in certain disease, especially when they origin from neural crest is considered. In this review, the specific characteristics and advantages of the adult dental stem cell population will be summarized and the molecular mechanisms of the differentiation of dental stem cell during tooth development will be also discussed.

Mesenchymal stem cells (MSCs) are ideal candidates for different cellular therapies due to their simple isolation, extensive expansion potential, and low immunogenicity. For various therapeutic approaches, such as bone and cartilage repair, MSCs are expected to replace the damaged tissues by direct differentiation. However, age-related changes in MSCs lead to the loss of differentiation potential, loss of proliferation potential and increase in senescent cell numbers, which involve a steady loss of bone mass and frequently result in osteoporosis. In this review, we will introduce the characteristic and age-related changes of MSCs. In addition, we will also summarize the potential rescue mechanisms of age-related bone loss involved in differentiation regulation and proliferation regulation, including transcription factors, signal pathways, epigenetic regulation, and oxidative stress regulation.

Embryonic stem cells (ES cells) hold great potential for regenerative medicine. Grasp of the underlying elaborate machinery is required for clinical application. MicroRNAs serve as important post-transcriptional regulators of various normal and pathological processes. Substantial headway has been made in deciphering miRNAs’ roles in establishment, maintenance and exit from pluripotency in ES cells. Here, we summarize current and ongoing research on microRNAs’ roles of pluripotency maintenance and germ layer specification and possible mechanism to script the cell fate.

Predictable and complete periodontal regeneration following periodontitis has been the ultimate goal of periodontal treatment. It has been recognized that Hertwig’s epithelial root sheath (HERS) cells play a crucial role in cementogenesis and root formation. As the descendants of HERS and unique odontogenic epithelium in the adult periodontium, epithelial cell rests of Malassez (ERM) have long been considered as quiescent epithelial remnants devoid of structure and function. Here we will present an overview of our present understanding and putative functions of the ERM in the regeneration of periodontal tissues.

Amelogenesis consists of various development phases that are tightly controlled by the exquisitely sequential and reciprocal interactions between tooth epithelium and mesenchyme. Subtle alterations during this complex physiological and biochemical development events could lead to severe enamel defects in shape, color and structure. Modulations in microRNA, DNA methylation and chromatin modifications are emerging as important regulatory mechanisms during tooth development. The growing field of epigenetic regulations in enamel development provides excellent opportunities to identify novel enamel-related disease makers and to explore the potential therapeutic methods. The present review will give an overview in the current research progress in epigenetic regulation events during tooth development with a highlight in the aspects of enamel formation.

Adult dental mesenchymal stem cells (DMSCs) are multi-potent stem cells that are involved in dental tissue repair and regeneration. DMSCs are able to differentiate into multiple lineages, including odontogenic, osteogenic, neurogenic, adipogenic, chondrogenic, hepatogenic lineages and insulinproducing cells. However, the DMSCs from functioning, impacted or exfoliated teeth may not be available when needed. Recently, DMSCs have been found in pulpal, periapical and periodontal tissue with inflammation from deciduous and immature/mature permanent teeth. DMSCs from inflamed tissue (iDMSCs) possess typical stem cell characteristics while they showing varied properties. Whether iDMSCs are comparable to healthy DMSCs and can be used for regeneration are not clear. Studies on the impact of infection/inflammation in the local microenvironment on DMSCs are widely conducted to investigate the specific influences and underlying mechanisms in vitro and in vivo. In this review, we introduced the discovery of iDMSCs from different sources, and also discussed the influence of dental inflammation and associated immune responses, particularly the effect from lipopolysaccharide (LPS) stimulation, on local DMSCs. In addition, the effects of dental procedures and materials on DMSCs are discussed.

MicroRNAs (miRNAs) are short (~21nt), noncoding, and single-stranded RNAs that can negatively regulate gene expression by binding to 3’UTRs of target mRNAs sequence-specifically to affect their translation and/or stability. MiRNAs are involved in multiple developmental events in various tissues and organs. Such events include dental enamel development. This review focuses on the expression and functions of miRNAs regulated in enamel development. This study further discusses the possible participation of signaling pathways affected by miRNAs during stem cell proliferation or renewal, cell differentiation, and cusp patterning formation. Research on the enamel developmental process and miRNA regulation mechanisms can facilitate better understanding of clinical enamel malformation and provide potential therapeutic schemes.

Overall enamel is the hard tissue overlying teeth that is vulnerable to caries, congenital defects, and damage due to trauma. Not only is enamel incapable of self-repair in most species, but it is also subject to attrition. Besides the use of artificial materials to restore enamel, enamel regeneration is a promising approach to repair enamel damage. In order to comprehend the progression and challenges in tissue-engineered enamel, this article elaborates alternative stem cells potential for enamel secretion and expounds fined strategies for enamel regeneration in bioengineered teeth. Consequently, more and more cell types have been induced to differentiate into ameloblasts and to secrete enamel, and an increasing number of reports have emerged to provide various potential approaches to induce cells to secrete enamel based on recombination experiments, artificial bioactive nano-materials, or gene manipulation. Accordingly, it is expected to further project more optimal conditions for enamel formation in bioengineering based on a more thorough knowledge of reciprocal epithelial-mesenchymal interactions, by which the procedures of enamel regeneration are able to be practically recapitulated and widely spread for the potential clinical value of enamel repair.

Stem cells are unspecialized cells, which have the capacity to self-renew and generate differentiated cell types. They hold great promises in regenerative medicine, which has the potential to revolutionize our approach to treat diseases and alleviate problems caused by trauma and aging. The dental field has been an active area for researching stem cell based therapies and a great effort has been made to develop strategies for utilizing embryonic stem cells (ESCs), adult dental stem cells and more recently, induced pluripotent stem (iPS) cells in tooth regeneration. In this review, we focus on these three main sources of stem cells, describe findings that have laid the foundation for using these cells in tooth regeneration, and discuss the potential as well as challenges of tooth bioengineering in clinical application.

Postnatal skeletogenesis is a highly regulated process that subpopulations of bone marrow stem cells differentiate into mature skeletal tissues to maintain and repair the postnatal skeletons. Based on their skeletogenic capacity, purified bone marrow stem cells have been used to repair and replace damaged skeletal tissues in recent years. In the meantime, significant effort has been devoted to unveil the nature and function of the “skeletogenic” precursors in vivo. In this review, we summarized our current understanding of the identification and fate-mapping of the stem cells contributing to postnatal skeletogenesis in the mouse bone marrow.

Osteogenic differentiation of skeletal stem cells is an integral part of bone development and homeostasis, and the perturbation of this process is one of the causes to skeletal disease. Understanding of how epigenetic events regulate skeletal stem cell differentiation is therefore of great importance. While the basic epigenetic modifications leading to bone formation are somewhat under explored, a significant amount of research has defined the regulatory roles of histone modifications in osteogenic differentiation. The orchestration of histone modifications is a requirement to establish the epigenetic status which regulates gene transcription during osteogenic differentiation of skeletal stem cells. Here we focus on the roles of histone modification during osteogenic differentiation and review studies that have advanced our knowledge in the field. Before this summary, a brief description is given regarding the up-to-date understanding of the definition of skeletal stem cells and the main mechanisms responsible for histone modifications.