Inhibition of lipopolysaccharide-induced NF-κB maintains osteogenesis of dental pulp and periodontal ligament stem cells.

Dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) can differentiate into osteoblasts, indicating that both are potential candidates for bone tissue engineering. Osteogenesis is influenced by many environmental factors, one of which is lipopolysaccharide (LPS). LPS-induced NF-κB activity affects the osteogenic potencies of different types of MSCs differently. This study evaluated the effect of LPS-induced NF-κB activity and its inhibition in DPSCs and PDLSCs. DPSCs and PDLSCs were cultured in an osteogenic medium, pretreated with/without NF-κB inhibitor Bay 11-7082, and treated with/without LPS. Alizarin red staining was performed to assess bone nodule formation, which was observed under an inverted light microscope. NF-κB and alkaline phosphatase (ALP) activities were measured to examine the effect of Bay 11-7082 pretreatment and LPS supplementation on osteogenic differentiation of DPSCs and PDLSCs. LPS significantly induced NF-κB activity (p = 0.000) and reduced ALP activity (p = 0.000), which inhibited bone nodule formation in DPSCs and PDLSCs. Bay 11-7082 inhibited LPS-induced NF-κB activity, and partially maintained ALP activity and osteogenic potency of LPS-supplemented DPSCs and PDLSCs. Thus, inhibition of LPS-induced NF-κB activity can maintain the osteogenic potency of DPSCs and PDLSCs.

Trophoblast stem cells, trophoblast invasion, and organoids - advancements in gynecology.

The human placenta serves as a vital barrier between the mother and the developing fetus during pregnancy. A defect in the early development of the placenta is associated with severe pregnancy disorders. Despite its complex development, various molecular processes control placental development, and the specialization of trophoblast cells is still not fully understood. One primary obstacle is the lack of suitable cell model systems. Traditional two-dimensional (2D) cell cultures fail to mimic in vivo conditions and do not capture the intricate intercellular interactions vital for studying placental development. However, three-dimensional (3D) organoid models derived from stem cells that replicate natural cell organization and architecture have greatly improved our understanding of trophoblast behavior and its medicinal applications. Organoids with relevant phenotypes provide a valuable platform to model both placental physiology and pathology, including the modeling of placental disorders. They hold great promise for personalized medicine, improved diagnostics, and the evaluation of pharmaceutical drug efficacy and safety. This article provides a concise overview of trophoblast stem cells, trophoblast invasion, and the evolving role of organoids in gynecology.

The effects of microgravity on stem cells and the new insights it brings to tissue engineering and regenerative medicine.

Conventional two-dimensional (2D) cell culture techniques may undergo modifications in the future, as life scientists have widely acknowledged the ability of three-dimensional (3D) in vitro culture systems to accurately simulate in vivo biology. In recent years, researchers have discovered that microgravity devices can address many challenges associated with 3D cell culture. Stem cells, being pluripotent cells, are regarded as a promising resource for regenerative medicine. Recent studies have demonstrated that 3D culture in microgravity devices can effectively guide stem cells towards differentiation and facilitate the formation of functional tissue, thereby exhibiting advantages within the field of tissue engineering and regenerative medicine. Furthermore, We delineate the impact of microgravity on the biological behavior of various types of stem cells, while elucidating the underlying mechanisms governing these alterations. These findings offer exciting prospects for diverse applications.

Muscle stem cell niche dynamics during muscle homeostasis and regeneration.

The process of skeletal muscle regeneration involves a coordinated interplay of specific cellular and molecular interactions within the injury site. This review provides an overview of the cellular and molecular components in regenerating skeletal muscle, focusing on how these cells or molecules in the niche regulate muscle stem cell functions. Dysfunctions of muscle stem cell-to-niche cell communications during aging and disease will also be discussed. A better understanding of how niche cells coordinate with muscle stem cells for muscle repair will greatly aid the development of therapeutic strategies for treating muscle-related disorders.

Role of microenvironment on muscle stem cell function in health, adaptation, and disease.

The role of the cellular microenvironment has recently gained attention in the context of muscle health, adaption, and disease. Emerging evidence supports major roles for the extracellular matrix (ECM) in regeneration and the dynamic regulation of the satellite cell niche. Satellite cells normally reside in a quiescent state in healthy muscle, but upon muscle injury, they activate, proliferate, and fuse to the damaged fibers to restore muscle function and architecture. This chapter reviews the composition and mechanical properties of skeletal muscle ECM and the role of these factors in contributing to the satellite cell niche that impact muscle regeneration. In addition, the chapter details the effects of satellite cell-matrix interactions and provides evidence that there is bidirectional regulation affecting both the cellular and extracellular microenvironment within skeletal muscle. Lastly, emerging methods to investigate satellite cell-matrix interactions will be presented.

Repair and regeneration of the alveolar epithelium in lung injury.

Considerable progress has been made in understanding the function of alveolar epithelial cells in a quiescent state and regeneration mechanism after lung injury. Lung injury occurs commonly from severe viral and bacterial infections, inhalation lung injury, and indirect injury sepsis. A series of pathological mechanisms caused by excessive injury, such as apoptosis, autophagy, senescence, and ferroptosis, have been studied. Recovery from lung injury requires the integrity of the alveolar epithelial cell barrier and the realization of gas exchange function. Regeneration mechanisms include the participation of epithelial progenitor cells and various niche cells involving several signaling pathways and proteins. While alveoli are damaged, alveolar type II (AT2) cells proliferate and differentiate into alveolar type I (AT1) cells to repair the damaged alveolar epithelial layer. Alveolar epithelial cells are surrounded by various cells, such as fibroblasts, endothelial cells, and various immune cells, which affect the proliferation and differentiation of AT2 cells through paracrine during alveolar regeneration. Besides, airway epithelial cells also contribute to the repair and regeneration process of alveolar epithelium. In this review, we mainly discuss the participation of epithelial progenitor cells and various niche cells involving several signaling pathways and transcription factors.

Decoding the forces that shape muscle stem cell function.

Skeletal muscle is a force-producing organ composed of muscle tissues, connective tissues, blood vessels, and nerves, all working in synergy to enable movement and provide support to the body. While robust biomechanical descriptions of skeletal muscle force production at the body or tissue level exist, little is known about force application on microstructures within the muscles, such as cells. Among various cell types, skeletal muscle stem cells reside in the muscle tissue environment and play a crucial role in driving the self-repair process when muscle damage occurs. Early evidence indicates that the fate and function of skeletal muscle stem cells are controlled by both biophysical and biochemical factors in their microenvironments, but much remains to accomplish in quantitatively describing the biophysical muscle stem cell microenvironment. This book chapter aims to review current knowledge on the influence of biophysical stresses and landscape properties on muscle stem cells in heath, aging, and diseases.

ID factors regulate the ability of Müller glia to become proliferating neurogenic progenitor-like cells.

The purpose of this study was to investigate how ID factors regulate the ability of Müller glia (MG) to reprogram into proliferating MG-derived progenitor cells (MGPCs) in the chick retina. We found that ID1 is transiently expressed by maturing MG (mMG), whereas ID4 is maintained in mMG in embryonic retinas. In mature retinas, ID4 was prominently expressed by resting MG, but following retinal damage ID4 was rapidly upregulated and then downregulated in MGPCs. By contrast, ID1, ID2, and ID3 were low in resting MG and then upregulated in MGPCs. Inhibition of ID factors following retinal damage decreased numbers of proliferating MGPCs. Inhibition of IDs, after MGPC proliferation, significantly increased numbers of progeny that differentiated as neurons. In damaged or undamaged retinas inhibition of IDs increased levels of p21Cip1 in MG. In response to damage or insulin+FGF2 levels of CDKN1A message and p21Cip1 protein were decreased, absent in proliferating MGPCs, and elevated in MG returning to a resting phenotype. Inhibition of notch- or gp130/Jak/Stat-signaling in damaged retinas increased levels of ID4 but not p21Cip1 in MG. Although ID4 is the predominant isoform expressed by MG in the chick retina, id1 and id2a are predominantly expressed by resting MG and downregulated in activated MG and MGPCs in zebrafish retinas. We conclude that ID factors have a significant impact on regulating the responses of MG to retinal damage, controlling the ability of MG to proliferate by regulating levels of p21Cip1, and suppressing the neurogenic potential of MGPCs.

Homeostatic regulation of renewing tissue cell populations via crowding control: stability, robustness and quasi-dedifferentiation.

To maintain renewing epithelial tissues in a healthy, homeostatic state, cell divisions and differentiation need to be tightly regulated. Mechanisms of homeostatic regulation often rely on crowding feedback control: cells are able to sense the cell density in their environment, via various molecular and mechanosensing pathways, and respond by adjusting division, differentiation, and cell state transitions appropriately. Here, we determine, via a mathematically rigorous framework, which general conditions for the crowding feedback regulation (i) must be minimally met, and (ii) are sufficient, to allow the maintenance of homeostasis in renewing tissues. We show that those conditions naturally allow for a degree of robustness toward disruption of regulation. Furthermore, intrinsic to this feedback regulation is that stem cell identity is established collectively by the cell population, not by individual cells, which implies the possibility of 'quasi-dedifferentiation', in which cells committed to differentiation may reacquire stem cell properties upon depletion of the stem cell pool. These findings can guide future experimental campaigns to identify specific crowding feedback mechanisms.

Adipose stem cell-derived exosomes promote wound healing by regulating the let-7i-5p/GAS7 axis.

BACKGROUND: Injury to skin tissue is devastating for human health, making it imperative to devise strategies for hastening wound healing. Normal wound healing is a complex process comprising overlapping steps, including hemostasis, inflammatory response, proliferation, and matrix remodeling. This study investigated the effects of adipose stem cell-derived exosomes (ADSC-exos) on wound healing and the underlying mechanisms. METHODS: In vitro hydrogen peroxide (H2O2)-treated human keratinocyte (HaCaT) cell lines and in vivo animal wound models were established for this purpose. The cell migration was assessed using transwell and wound healing assays, while exosome biomarker expressions were studied using western blot. Moreover, adipose stem cells were identified using flow cytometry, alizarin red S and oil red O staining, and transmission electron microscopy. RESULTS: Results indicated that H2O2 treatment inhibited the cell viability and migration of HaCaT cells while being promoted by ADSC-exos. Mechanistic investigations revealed that microRNA-let-7i-5p (let-7i-5p) in ADSC-exos was carried into the HaCaT cells, inhibiting the expression of growth arrest-specific-7 (GAS7). Rescue experiments further verified these results, which indicated that GAS7 overexpression reversed the effect of let-7i-5p on the viability and migration of HaCaT cells, suggesting ADSC-exos promoted wound healing via the let-7i-5p/GAS7 axis. CONCLUSION: Adipose stem cell-derived-exos enhanced the viability and migration of HaCaT via carrying let-7i-5p and targeting GAS7, ultimately promoting wound healing in rats.

The Transplantation of 3-Dimensional Spheroids of Adipose-Derived Stem Cells Promotes Achilles Tendon Healing in Rabbits by Enhancing the Proliferation of Tenocytes and Suppressing M1 Macrophages.

BACKGROUND: Tendons have limited regenerative potential, so healing of ruptured tendon tissue requires a prolonged period, and the prognosis is suboptimal. Although stem cell transplantation-based approaches show promise for accelerating tendon repair, the resultant therapeutic efficacy remains unsatisfactory. HYPOTHESIS: The transplantation of stem cells preassembled as 3-dimensional spheroids achieves a superior therapeutic outcome compared with the transplantation of single-cell suspensions. STUDY DESIGN: Controlled laboratory study. METHODS: Adipose-derived stem cells (ADSCs) were assembled as spheroids using a methylcellulose hydrogel system. The secretome of ADSC suspensions or spheroids was collected and utilized to treat tenocytes and macrophages to evaluate their therapeutic potential and investigate the mechanisms underlying their effects. RNA sequencing was performed to investigate the global difference in gene expression between ADSC suspensions and spheroids in an in vitro inflammatory microenvironment. For the in vivo experiment, rabbits that underwent Achilles tendon transection, followed by stump suturing, were randomly assigned to 1 of 3 groups: intratendinous injection of saline, rabbit ADSCs as conventional single-cell suspensions, or preassembled ADSC spheroids. The tendons were harvested for biomechanical testing and histological analysis at 4 weeks postoperatively. RESULTS: Our in vitro results demonstrated that the secretome of ADSCs assembled as spheroids exhibited enhanced modulatory activity in (1) tenocyte proliferation (P = .015) and migration (P = .001) by activating extracellular signal-regulated kinase (ERK) signaling and (2) the suppression of the secretion of interleukin-6 (P = .005) and interleukin-1α (P = .042) by M1 macrophages via the COX-2/PGE2/EP4 signaling axis. Gene expression profiling of cells exposed to an inflammatory milieu revealed significantly enriched terms that were associated with the immune response, cytokines, and tissue remodeling in preassembled ADSC spheroids. Ex vivo fluorescence imaging revealed that the engraftment efficiency of ADSCs in the form of spheroids was higher than that of ADSCs in single-cell suspensions (P = .003). Furthermore, the transplantation of ADSC spheroids showed superior therapeutic effects in promoting the healing of sutured stumps, as evidenced by improvements in the tensile strength (P = .019) and fiber alignment (P < .001) of the repaired tendons. CONCLUSION: The assembly of ADSCs as spheroids significantly advanced their potential to harness tenocytes and macrophages. As a proof of concept, this study clearly demonstrates the effectiveness of using ADSC spheroids to promote tendon regeneration. CLINICAL RELEVANCE: The present study lays a foundation for future clinical applications of stem cell spheroid-based therapy for the management of tendon injuries.

Ang1/Tie2/VE-Cadherin Signaling Regulates DPSCs in Vascular Maturation.

Adding dental pulp stem cells (DPSCs) to vascular endothelial cell-formed vessel-like structures can increase the longevity of these vessel networks. DPSCs display pericyte-like cell functions and closely assemble endothelial cells (ECs). However, the mechanisms of DPSC-derived pericyte-like cells in stabilizing the vessel networks are not fully understood. In this study, we investigated the functions of E-DPSCs, which were DPSCs isolated from the direct coculture of human umbilical vein endothelial cells (HUVECs) and DPSCs, and T-DPSCs, which were DPSCs treated by transforming growth factor beta 1 (TGF-ß1), in stabilizing blood vessels in vitro and in vivo. A 3-dimensional coculture spheroid sprouting assay was conducted to compare the functions of E-DPSCs and T-DPSCs in vitro. Dental pulp angiogenesis in the severe combined immunodeficiency (SCID) mouse model was used to explore the roles of E-DPSCs and T-DPSCs in vascularization in vivo. The results demonstrated that both E-DPSCs and T-DPSCs possess smooth muscle cell-like cell properties, exhibiting higher expression of the mural cell-specific markers and the suppression of HUVEC sprouting. E-DPSCs and T-DPSCs inhibited HUVEC sprouting by activating TEK tyrosine kinase (Tie2) signaling, upregulating vascular endothelial (VE)-cadherin, and downregulating vascular endothelial growth factor receptor 2 (VEGFR2). In vivo study revealed more perfused and total blood vessels in the HUVEC + E-DPSC group, HUVEC + T-DPSC group, angiopoietin 1 (Ang1) pretreated group, and vascular endothelial protein tyrosine phosphatase (VE-PTP) inhibitor pretreated group, compared to HUVEC + DPSC group. In conclusion, these data indicated that E-DPSCs and T-DPSCs could stabilize the newly formed blood vessels and accelerate their perfusion. The critical regulating pathways are Ang1/Tie2/VE-cadherin and VEGF/VEGFR2 signaling.

Cell replacement therapy with stem cells in multiple sclerosis, a systematic review.

Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system (CNS), characterized by demyelination and axonal loss. It is induced by attack of autoreactive lymphocytes on the myelin sheath and endogenous remyelination failure, eventually leading to accumulation of neurological disability. Disease-modifying agents can successfully address inflammatory relapses, but have low efficacy in progressive forms of MS, and cannot stop the progressive neurodegenerative process. Thus, the stem cell replacement therapy approach, which aims to overcome CNS cell loss and remyelination failure, is considered a promising alternative treatment. Although the mechanisms behind the beneficial effects of stem cell transplantation are not yet fully understood, neurotrophic support, immunomodulation, and cell replacement appear to play an important role, leading to a multifaceted fight against the pathology of the disease. The present systematic review is focusing on the efficacy of stem cells to migrate at the lesion sites of the CNS and develop functional oligodendrocytes remyelinating axons. While most studies confirm the improvement of neurological deficits after the administration of different stem cell types, many critical issues need to be clarified before they can be efficiently introduced into clinical practice.

Citric Acid Conditioning as an Alternative to EDTA for Growth Factors Release and Stem Cell Response in Regenerative Endodontics: A Systematic Review of In Vitro Studies.

INTRODUCTION: Citric acid (CA) conditioning may be a promising alternative to ethylenediaminetetraacetic acid (EDTA) in regenerative endodontic procedures, as reported to improve growth factors' release from dentin. This review systematically investigated the effect of CA conditioning on the growth factors release from dentin and cell behavior compared to EDTA conditioning. METHODS: Searches were conducted (PubMed/MEDLINE, Scopus, Web of Science, Embase, SciELO, Cochrane Library, and grey literature) until May-2023. Only in vitro studies that evaluated the effects of CA on growth factors' release from dentin and cell behavior outcomes compared to EDTA were included. The studies were critically appraised using a modified Joanna Briggs Institute's checklist. Meta-analysis was unfeasible. RESULTS: Out of the 335 articles screened, nine were included. Among these, three studies used dentin discs/roots from permanent human teeth; the rest combined them with stem cells. 10% CA for 5 or 10 minute was the most used protocol. Meanwhile, EDTA concentrations ranged from 10% to 17%. In eight studies examining the release of growth factors, five reported a significant release of transforming growth factor-ß after dentin conditioning with 10% CA compared to 17% EDTA. Regarding cell behavior (6 studies), three studies assessed cell viability. The findings revealed that 10% CA conditioning showed cell viability similar to those of 17% EDTA. Additionally, in two out of three studies, it was observed that 10% CA conditioning did not affect cell morphology. The studies had a low risk of bias. CONCLUSIONS: The use of 10% CA to condition dentin for 5-10 minutes resulted in a notable transforming growth factor -ß1 release, but its cell responses were similar to those of EDTA.

Interactions of Neuronally Induced Stem Cells from Apical Papilla Spheres, Stems Cells from Apical Papilla, and Human Umbilical Vascular Endothelial Cells on Vasculogenesis and Neurogenesis.

INTRODUCTION: Stem cell-based dental pulp regeneration has been extensively studied, mainly focusing on exploiting dental stem cells' osteogenic and angiogenic potentials. Dental stem cells' neurogenic role is often overlooked. Stem cells from apical papilla (SCAPs), originating from the neural crest and capable of sphere formation, display potent neurogenic capacity. This study aimed to investigate the interactions of neuronally induced stem cells from apical papilla (iSCAP) spheres, SCAPs, and human umbilical vascular endothelial cells (HUVECs) on vasculogenesis and neurogenesis. METHODS: SCAPs were isolated and characterized using flow cytometry and multilineage differentiation assays. SCAP monolayer culture and spheres were neuronally induced by a small molecule neural induction medium, and the neural gene expression and neurite formation at days 0, 3, and 7 were evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and using phase-contrast light and fluorescence microscopy. Direct coculture or pulp-on-chip was used to investigate iSCAP sphere interaction with SCAPs and HUVECs. RT-qPCR, fluorescence microscopy, and immunostaining with ß-tubulin III, alpha-smooth muscle actin, and CD31 were used to study neural gene expression, neurite formation, and neurovascular cell interactions. RESULTS: Neural induction medium with small molecules rapidly induced SCAP differentiation toward neural-like cells. Gene expression of Nestin, ß-tubulin III, microtubule-associated protein 2, neuron-specific enolase, and NeuN was higher in iSCAP spheres than in iSCAPs. iSCAP spheres formed more and longer neurites compared with iSCAPs. iSCAP sphere, HUVEC, and SCAP direct coculture significantly enhanced vessel formation along with up-regulated VEGF (P < .001) and multiple neural markers, such as Nestin (P < .01), microtubule-associated protein 2 (P < .001), S100 (P < .001), and NG2 (P < .001). iSCAP spheres, SCAPs, and HUVECs cultured in a pulp-on-chip system promoted endothelial and neural cell migration toward each other and alpha-smooth muscle actin-positive and CD31-positive cells assembling for the vascular constitution. CONCLUSIONS: iSCAP-formed spheres interact with SCAPs and HUVECs, promoting vasculogenesis and neurogenesis.

Exploring the impact of oral bacteria remnants on stem cells from the Apical papilla: mineralization potential and inflammatory response.

Introduction: Bacterial persistence is considered one of the main causal factors for regenerative endodontic treatment (RET) failure in immature permanent teeth. This interference is claimed to be caused by the interaction of bacteria that reside in the root canal with the stem cells that are one of the essentials for RET. The aim of the study was to investigate whether prolonged exposure of stem cells from the apical papilla (SCAP) to bacterial remnants of Fusobacterium nucleatum, Actinomyces gerensceriae, Slackia exigua, Enterococcus faecalis, Peptostreptococcaceae yurii, commonly found in infected traumatized root canals, and the probiotic bacteria Lactobacillus gasseri and Limosilactobacillus reuteri, can alter SCAP's inflammatory response and mineralization potential. Methods: To assess the effect of bacterial remnants on SCAP, we used UV-C-inactivated bacteria (as cell wall-associated virulence factors) and bacterial DNA. Histochemical staining using Osteoimage Mineralization Assay and Alizarin Red analysis was performed to study SCAP mineralization, while inflammatory and osteo/odontogenic-related responses of SCAPs were assessed with Multiplex ELISA. Results: We showed that mineralization promotion was greater with UV C-inactivated bacteria compared to bacterial DNA. Immunofluorescence analysis detected that the early mineralization marker alkaline phosphatase (ALP) was increased by the level of E. coli lipopolysaccharide (LPS) positive control in the case of UV-C-inactivated bacteria; meanwhile, DNA treatment decreased the level of ALP compared to the positive control. SCAP's secretome assessed with Multiplex ELISA showed the upregulation of pro-inflammatory factors IL-6, IL-8, GM-CSF, IL-1b, neurotrophic factor BDNF, and angiogenic factor VEGF, induced by UV-C-killed bacteria. Discussion: The results suggest that long term stimulation (for 21 days) of SCAP with UV-C-inactivated bacteria stimulate their mineralization and inflammatory response, while DNA influence has no such effect, which opens up new ideas about the nature of RET failure.

Paracrine Responses of Cardiosphere-Derived Cells to Cytokines and TLR Ligands: A Comparative Analysis.

Cardiosphere-derived cells (CDCs) are currently being evaluated in clinical trials as a potential therapeutic tool for regenerative medicine. The effectiveness of transplanted CDCs is largely attributed to their ability to release beneficial soluble factors to enhance therapeutic effects. An emerging area of research is the pretreatment of stem cells, including CDCs, with various cytokines to improve their therapeutic properties. This strategy aims to enhance their survival, proliferation, differentiation, and paracrine activities after transplantation. In our study, we investigated the differential effects of various cytokines and TLR ligands on the secretory phenotype of human CDCs. Using a magnetic bead-based immunoassay, we analyzed the CDCs-conditioned media for 41 cytokines and growth factors and detected the presence of 21 cytokines. We found that CDC incubation with lipopolysaccharide, a TLR4 ligand, and the cytokine combination of TNF/IFN significantly increased the secretion of most of the cytokines detected. Specifically, we observed an increased secretion and gene expression of IP10, MCP3, IL8, and VEGFA. In contrast, the TLR3 ligand polyinosinic-polycytidylic acid and TGF-beta had minimal effects on CDC cytokine secretion. Additionally, TNF/IFN, but not LPS, enhanced ICAM1 expression. Our findings offer new insights into the role of cytokines in potentially modulating the biology and regenerative potential of CDCs.

Folate-depletion alters mouse trophoblast stem cell regulation in vitro.

Maternal folate deficiency increases risk of congenital malformations, yet its effect on placenta development is unclear. Here, we investigated how folate-depleted culture medium affects the developmental potential of mouse trophoblast stem cells (TSCs). When cultured in stem cell conditions, TSC viability was unaffected by folate depletion, but ectopic differentiation of trophoblast cell subtypes occurred. When cultured in conditions that promote differentiation, folate-depleted TSCs were driven towards a syncytiotrophoblast cell fate potentially at the expense of other lineages. Additionally, trophoblast giant cell nuclei were small implicating folate in the regulation of endoreduplication. Therefore, dietary folate intake likely promotes trophoblast development.

Stem cells in clinical dentistry.

BACKGROUND: Stem cells are present in most of the tissues in the craniofacial complex and play a major role in tissue homeostasis and repair. These cells are characterized by their capacity to differentiate into multiple cell types and to self-renew to maintain a stem cell pool throughout the life of the tissue. TYPES OF STUDIES REVIEWED: The authors discuss original data from experiments and comparative analyses and review articles describing the identification and characterization of stem cells of the oral cavity. RESULTS: Every oral tissue except enamel, dentin, and cementum contains stem cells for the entire life span. These stem cells self-renew to maintain a pool of cells that can be activated to replace terminally differentiated cells (for example, odontoblasts) or to enable wound healing (for example, dentin bridge in pulp exposures and healing of periodontal tissues after surgery). In addition, dental stem cells can differentiate into functional blood vessels and nerves. Initial clinical trials have shown that transplanting dental pulp stem cells into disinfected necrotic teeth has allowed for the recovery of tooth vitality and vertical and horizontal root growth in immature teeth with incomplete root formation. PRACTICAL IMPLICATIONS: As a consequence of these groundbreaking discoveries, stem cell banks are now offering services for the cryopreservation of dental stem cells. The future use of stem cell-based therapies in the clinic will depend on the collaboration of clinicians and researchers in projects designed to understand whether these treatments are safe, efficacious, and clinically feasible.