Epithelial Cell Rests Research Articles

The characteristics of epithelial cell rests of Malassez during tooth eruption of development mice

It has been demonstrated that Hertwig's epithelial root sheath (HERS) has an important role in root development, closely related to development of cementum epithelial rests of Malassez (ERM) as the residuum after HERS fragment, and is the exclusive epithelial structure in the mature periodontal ligament. Some studies reported that ERM may play a role in maintaining a stable environment of periodontal, and likely to be involved in regeneration of periodontal tissue, especially of cementum. However, the function of the ERM is not well understood. In this study, we observed the morphology and biological characteristics of ERM of the maxillary 1st molar with surrounding periodontal tissues of BALB/c mice during the period of tooth cusp erupted out of the gingiva to occlusion stability. Immunohistochemistry revealed ERM predominately located at the cervical and root furcation regions of the periodontal ligament. The number of ERM cells at the cervical and root furcation regions of the post-built occlusion stage decreased compared to pre-built occlusion stage and occlusion building stage. Transmission electron microscopy analysis showed that epithelial cell nuclei with typical features of apoptosis were observed at the post-built occlusion stage, and consistent with positive bodies labeled by TUNEL(terminal deoxy-transferase (TdT)-mediated dUTP-biotin nick end labeling), while proliferating cell nuclear antigen positive bodies mainly located at occlusion built stage. It suggests that ERM may regulate in alveolar bone remodeling in association with the periodontal ligament during tooth erupting to occlusion stability and may play important roles potentially in regeneration and homeostasis of the periodontal tissues.

Epithelial Cell Rests of Malassez Contain Unique Stem Cell Populations Capable of Undergoing Epithelial–Mesenchymal Transition

The epithelial cell rests of Malassez (ERM) are odontogenic epithelial cells located within the periodontal ligament matrix. While their function is unknown, they may support tissue homeostasis and maintain periodontal ligament space or even contribute to periodontal regeneration. We investigated the notion that ERM contain a subpopulation of stem cells that could undergo epithelial-mesenchymal transition and differentiate into mesenchymal stem-like cells with multilineage potential. For this purpose, ERM collected from ovine incisors were subjected to different inductive conditions in vitro, previously developed for the characterization of bone marrow mesenchymal stromal/stem cells (BMSC). We found that ex vivo-expanded ERM expressed both epithelial (cytokeratin-8, E-cadherin, and epithelial membrane protein-1) and BMSC markers (CD44, CD29, and heat shock protein-90β). Integrin α6/CD49f could be used for the enrichment of clonogenic cell clusters [colony-forming units-epithelial cells (CFU-Epi)]. Integrin α6/CD49f-positive-selected epithelial cells demonstrated over 50- and 7-fold greater CFU-Epi than integrin α(6)/CD49f-negative cells and unfractionated cells, respectively. Importantly, ERM demonstrated stem cell-like properties in their differentiation capacity to form bone, fat, cartilage, and neural cells in vitro. When transplanted into immunocompromised mice, ERM generated bone, cementum-like and Sharpey's fiber-like structures. Additionally, gene expression studies showed that osteogenic induction of ERM triggered an epithelial-mesenchymal transition. In conclusion, ERM are unusual cells that display the morphological and phenotypic characteristics of ectoderm-derived epithelial cells; however, they also have the capacity to differentiate into a mesenchymal phenotype and thus represent a unique stem cell population within the periodontal ligament.

Responses of BrdU label-retaining dental pulp cells to allogenic tooth transplantation into mouse maxilla

Recently, we demonstrated that a pulse of BrdU given to prenatal animals reveals the existence of slow-cycling long-term label-retaining cells (LRCs), putative adult stem or progenitor cells, which reside in the dental pulp. This study aims to clarify responses of LRCs to allogenic tooth transplantation into mouse maxilla using prenatal BrdU-labeling, in situ hybridization for osteopontin and periostin, and immunohistochemistry for BrdU, nestin, and osteopontin. The upper-right first molars were allografted in the original socket between BrdU-labeled and non-labeled mice or between GFP transgenic and wild-type mice. Tooth transplantation caused degeneration of the odontoblast layer, resulting in the disappearance of nestin-positive reactions in the dental pulp. On postoperative days 5-7, tertiary dentin formation commenced next to the preexisting dentin where nestin-positive odontoblast-like cells were arranged in the successful cases. In BrdU-labeled transplanted teeth, dense LRCs were maintained in the center of the dental pulp beneath the odontoblast-like cells including LRCs, whereas LRCs disappeared in the area surrounding the bone-like tissue. In contrast, LRCs were not recognized in the pulp chamber of non-labeled transplants through the experimental period. Tooth transplantation using GFP mice demonstrated that the donor cells constituted the dental pulp of the transplant except for endothelial cells and some migrated cells, and the periodontal tissue was replaced by host-derived cells except for epithelial cell rests of Malassez. These results suggest that the maintenance of BrdU label-retaining dental pulp cells play a role in the regeneration of odontoblast-like cells in the process of pulpal healing following tooth transplantation.

The effect of aging on the functions of epithelial rest cells of Malassez in vitro: immunofluorescence, DNA microarray and RT-PCR analyses

Background: The major function of Malassez's epithelial rest (ERM) cells is thought to be maintenance of the homeostasis of the periodontal ligament. The purpose of this study was to investigate the effect of aging on the functions of ERM cells in vitro. Methods: ERM cells cultured from porcine teeth were used in this study, and cells at passages 3, 11 and 17 were analyzed by DNA microarray to evaluate gene expression profiles. Furthermore, quantitative real-time RT-PCR was performed to confirm the microarray data for selected genes. Results: The microarray data revealed that approximately 4,300 of the 21,123 genes on the array were expressed at significantly different levels. Among them, 230 genes, including BMP2, were significantly decreased between the 3rd to the 11th passage. Moreover, 23 genes, including beta-defensin1, MMP13 and CD61, were significantly down-regulated from the 3rd to the 11th and from the 11th to the 17th passages(P<0.05). Conclusion: These results suggest that cementogenesis, antibacterial effects, collagenase activity and cell adhesive functions of the ERM are affected by aging.

Epithelial Cell Rests of Malassez Modulate Cell Proliferation, Differentiation and Apoptosis via Gap Junctional Communication under Mechanical Stretching in vitro

Epithelial cell rests of Malassez (ERM) are involved in the maintenance and homeostasis of the periodontal ligament. The objective of this study was to investigate the effect of mechanical stretching on cell growth, cell death and differentiation in the ERM. Cultured porcine ERM were stretched for 24 hr in cycles of 18% elongation for 1 sec followed by 1 sec relaxation. The numbers of cells and TUNEL-positive cells were then counted. The expression of mRNAs encoding gap junction protein α1 (Gja1), ameloblastin, bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 4 (BMP4) and noggin were evaluated using quantitative real-time PCR. The number of cells in the stretching group was approximately 1.3-fold higher than that in the non-stretching controls at 24 hr (p<0.01). Apoptotic cells ranged from 1.9-2.5% in the stretching group at 24 hr, but were only 0.6% in the control group (p<0.01). The expression of Gja1, ameloblastin and noggin mRNAs in the stretching group was decreased at 24 hr compared with in the non-stretching group (p<0.01), whereas the expression of BMP2 and BMP4 mRNAs in the stretching group was significantly higher than that in the control group (p<0.01). Incorporation of 18 α-glycyrrhetinic acid (18GA, a gap junction inhibitor) promoted proliferation and apoptosis and confirmed both the increase of BMP2 and BMP4 and the decline of Gja1, ameloblastin and noggin in ERM. Thus, the ERM modulate cell proliferation and apoptosis, and inhibit differentiation by reducing expression of Gja1 under mechanical stretching.

Disruption of periodontal integrity induces expression of apin by epithelial cell rests of Malassez

It has been suggested that epithelial cell rests of Malassez (ERM) may express enamel matrix proteins and play an important role in periodontal regeneration. Two novel proteins, apin (APIN) and amelotin (AMTN), produced by maturation-stage ameloblasts and junctional epithelium, have recently been identified. The objective of this study was to evaluate whether the ERM express APIN and AMTN under normal conditions and after periodontal challenge. Gingivectomy and orthodontic tooth movement were carried out on the left side of the maxillae of rats. The control group included the untreated contralateral side of these animals and the maxillae of normal, untreated rats. Animals were sacrificed by intracardiac perfusion on days 3 and 5 after the experimental procedures and maxillary molars were decalcified and processed for paraffin embedding. Immunohistochemistry was used to evaluate the expression of various ameloblast products, including APIN, AMTN, ameloblastin (AMBN) and amelogenin (AMEL). At 3 and 5 days after periodontal challenge, ERM were more evident in the periodontal ligament along the root surface and in the root furcations. Immunodetection of APIN, but not of the other three proteins, was observed in the ERM following the disruption of periodontal integrity. No immunolabeling for APIN, AMTN, AMBN and AMEL was detected in the ERM under normal conditions. The expression of APIN at an early time-point following disruption of periodontal integrity suggests that this protein may be part of the cascade of events leading to the activation of ERM during periodontal healing and regeneration.

Effects of epidermal growth factor and/or nerve growth factor on Malassez’s epithelial rest cellsin vitro: expression of mRNA for osteopontin, bone morphogenetic protein 2 and vascular endothelial growth factor

Malassez's epithelial rest (MER) cells are involved in the maintenance and homeostasis of the periodontal ligament (PDL). The purpose of this study was to determine the effects of epidermal growth factor (EGF) and/or nerve growth factor (NGF) in vitro on these functions of MER cells. MER cells from porcine PDL were incubated for 3 or 9 h after the addition of EGF and/or NGF to final concentrations of 10 ng/mL. Cells cultured without those growth factors were used as controls. The expression of mRNA for osteopontin, bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) was analyzed using quantitative RT-PCR. There was a decrease in the expression of osteopontin mRNA by MER cells treated for 9 h with NGF and the level of mRNA expressed was lower than that of the control and EGF-treated groups. The expression of BMP-2 mRNA by MER cells treated with NGF for 9 h also decreased, and was lower than that of the control and EGF-treated groups. The expression of VEGF mRNA by MER cells treated with EGF for 3 or 9 h was higher than in the control and NGF-treated groups. The expression of VEGF mRNA was lower in MER cells treated with NGF for 3 and 9 h than in the control and EGF-treated groups, and decreased from 3 to 9 h of treatment. EGF stimulated MER cells to secrete VEGF, which suggests that EGF plays an important role in maintaining the homeostasis of the PDL. NGF acts on MER cells to inhibit calcification in the PDL. Furthermore, in the EGF+NGF-treated MER cells, expression of mRNA for BMP-2 and VEGF was similar to that of the NGF-treated group, but cell proliferation and expression of osteopontin mRNA were similar to that of the EGF-treated group. EGF and NGF play important roles in maintaining the PDL.

Disease-Associated Prion Protein in the Dental Tissue of Mice Infected with Scrapie

Transmissible spongiform encephalopathies (TSEs) induce fatal neurodegenerative diseases in man and animals. The present study demonstrates immunohistochemically the presence of disease-associated prion protein (PrP(Sc)) in the epithelial cell rests of Malassez (ERM) of mice experimentally infected with ME7 scrapie by the intracerebral route. Mouse bioassay of scrapie-infected dental tissue revealed prolonged incubation periods, suggesting that there are relatively low amounts of infectious agent in dental tissue compared with the brain. These findings indicate that PrP(Sc) may spread from the brain to the ERM along the cranial nerves via the trigeminal ganglion that innervates the dental tissues. Dental tissue might therefore be a potential source of PrP(Sc) for horizontal transmission of TSEs.

Effect of Stretching Force on the Cells of Epithelial Rests of Malassez In Vitro

Background and Objective. The aim of this study was to investigate the behavior of cells from epithelial rest of Malassez (ERM) against stretching force. Material and Methods. ERM-cultured cells were stretched for 1 hour, at the cycle of 18% elongation for 1 second followed by 1-second relaxation. The cells without addition of stretching force were used as controls. The cells were observed by immunohistochmical staining using actin 0, 12, 24, 36, 48, and 72 hours. Furthermore, expressions of HSP70-, VEGF-, and OPN-mRNAs of cells were also evaluated using quantitative RT-PCR. Results. Actin filaments were randomly orientated in the cytoplasm in the control group, whereas in the stretching group, actin filaments were orientated comparatively parallel to the stretching direction. Expression of HSP70-mRNA in the stretching group was significantly higher than that of control group at 12, 24, 36 hours (P < .05). Expression of VEGF-mRNA in the stretching group was significantly higher than that of control group at 24, 36, 48, and 72 hours (P < .05). Expression of OPN-mRNA in the stretching group was significantly higher than that of control group at 12 and 24 hours (P < .05). Conclusion. ERM cells response against the stretching force by expressing HSP70, VEGF, and OPN.

Uncommon synchronous histopathological features of a radicular cyst: a case report.

Radicular cysts are the most common inflammatory odontogenic cystic lesions. It originates from epithelial residues in periodontal ligaments secondary to inflammation. The pathogenesis involves the activation of epithelial cell rests of Malaseez after physical, chemical or bacterial injury. Microscopically, the cyst is thin with smooth or corrugated inner surface. The most common epithelial lining is stratified squamous; with Rushton's hyaline bodies in 10% of the reported cases. Slow accumulation and deposition of cholesterol during the inflammatory process leads to the formation of "clefts" with acute and chronic inflammatory cells in the proliferating epithelium and connective tissue, respectively. The presence of hemosiderin usually indicates a previous micro-hemorrhage event. While the presence of lipid-laden macrophages or foam cells indicate the presence of cholesterol-removing mechanism from the lesion. We report a rare case of 38-year-old Mediterranean female presented with throbbing right maxillary pain. The diagnosis of radicular cyst was confirmed by the presence of atrophic non-keratinized stratified squamous epithelium. The radicular cyst was associated with hemosiderin, foam cells, subepithelial fibrosis and root canal dystrophic calcification. They represent uncommon synchronous histopathological features.

Effects of nicotine on Malassez' epithelial rest cells in early primary culture: cell proliferation and mRNA expression of heat shock protein 70 and vascular endothelial growth factor

The purpose of this study was to evaluate the effects of nicotine on Malassez' epithelial rest (MER) cells which are thought to maintain the homeostasis of the periodontal ligament. MER cells obtained from porcine periodontal ligament were cultured for 7 days, after which nicotine was added to the culture medium at concentrations of 0.03 μM, 0.15 μM or 0.2 μM. Cells cultured without nicotine were used as controls. Cell proliferation and expression of mRNAs encoding heat shock protein 70 (HSP70) and vascular endothelial growth factor (VEGF) were analyzed to evaluate the effects of nicotine. The cell proliferation ratios of all nicotine-treated groups were significantly lower than the control group on day 7. The expression of HSP70 mRNA in all nicotine-treated groups was higher than in the control group. The expression of VEGF mRNA in all nicotine-treated groups at all times examined tended to be lower than in the control groups. In conclusion, nicotine affects MER cells by increasing mRNA expression of HSP70, but decreasing that of VEGF.

Uncommon synchronous histopathological features of a radicular cyst: a case report

Radicular cysts are the most common inflammatory odontogenic cystic lesions. It originates from epithelial residues in periodontal ligaments secondary to inflammation. The pathogenesis involves the activation of epithelial cell rests of Malaseez after physical, chemical or bacterial injury. Microscopically, the cyst is thin with smooth or corrugated inner surface. The most common epithelial lining is stratified squamous; with Rushton's hyaline bodies in 10% of the reported cases. Slow accumulation and deposition of cholesterol during the inflammatory process leads to the formation of "clefts" with acute and chronic inflammatory cells in the proliferating epithelium and connective tissue, respectively. The presence of hemosiderin usually indicates a previous micro-hemorrhage event. While the presence of lipid-laden macrophages or foam cells indicate the presence of cholesterol-removing mechanism from the lesion. We report a rare case of 38-year-old Mediterranean female presented with throbbing right maxillary pain. The diagnosis of radicular cyst was confirmed by the presence of atrophic non-keratinized stratified squamous epithelium. The radicular cyst was associated with hemosiderin, foam cells, subepithelial fibrosis and root canal dystrophic calcification. They represent uncommon synchronous histopathological features.

Quiescent epithelial cell rests of Malassez can differentiate into ameloblast‐like cells

Epithelial cell rests of Malassez (ERM) are quiescent epithelial remnants of Hertwig's epithelial root sheath (HERS) that are involved in the formation of tooth roots. After completion of crown formation, HERS are converted from cervical loop cells, which have the potential to generate enamel for tooth crown formation. Cervical loop cells have the potential to differentiate into ameloblasts. Generally, no new ameloblasts can be generated from HERS, however this study demonstrated that subcultured ERM can differentiate into ameloblast-like cells and generate enamel-like tissues in combination with dental pulp cells at the crown formation stage. Porcine ERM were obtained from periodontal ligament tissue by explant culture and were subcultured with non-serum medium. Thereafter, subcultured ERM were expanded on 3T3-J2 feeder cell layers until the tenth passage. The in vitro mRNA expression pattern of the subcultured ERM after four passages was found to be different from that of enamel organ epithelial cells and oral gingival epithelial cells after the fourth passage using the same expansion technique. When subcultured ERM were combined with subcultured dental pulp cells, ERM expressed cytokeratin14 and amelogenin proteins in vitro. In addition, subcultured ERM combined with primary dental pulp cells seeded onto scaffolds showed enamel-like tissues at 8 weeks post-transplantation. Moreover, positive staining for amelogenin was observed in the enamel-like tissues, indicating the presence of well-developed ameloblasts in the implants. These results suggest that ERM can differentiate into ameloblast-like cells.

In Vitro Characterization of the Cytokine Profile of the Epithelial Cell Rests of Malassez

The epithelial cell rests of Malassez (ERM) are an integral part of the periodontal ligament and are considered to play an important role in dental pathology. Surprisingly, this cell type is poorly described and is often disregarded in the context of periodontal research. The aim of this study was to establish primary cell cultures of human ERM, characterize the cytokine profile, and compare it to other periodontal cell entities. ERM-derived epithelial cells were isolated from the periodontal ligament of three subjects. A cytokine antibody array, including 120 cytokines in two membranes, was used to determine the cytokine profile of conditioned medium from the ERM-derived epithelial cells. The results were compared to those of gingival epithelial cells and periodontal ligament fibroblasts. ERM-derived epithelial cells expressed 29 of 120 cytokines in significant amounts, including cytokines, chemokines, growth factors, and related proteins, such as interleukin (IL)-1, -6, -8, and -10; granulocyte macrophage-colony stimulating factor; monocyte chemoattractant protein (MCP)-1, -2, and -3; amphiregulin; glial-derived neurotrophic factor; vascular endothelial growth factor; and insulin-like growth factor binding protein-2. The cytokine profile of ERM cells was similar to that of gingival epithelial cells but strikingly different from the profile of periodontal ligament fibroblasts. The results indicated that, via paracrine secretion of a variety of soluble factors, the ERM cells actively take part in the homeostasis of the periodontium. Therefore, future research on the pathophysiology of periodontal tissue should include this often overlooked cell type.

Observations on continuously growing roots of the sloth and the K14‐Eda transgenic mice indicate that epithelial stem cells can give rise to both the ameloblast and root epithelium cell lineage creating distinct tooth patterns

Root development is traditionally associated with the formation of Hertwig's epithelial root sheath (HERS), whose fragments give rise to the epithelial cell rests of Malassez (ERM). The HERS is formed by depletion of the core of stellate reticulum cells, the putative stem cells, in the cervical loop, leaving only a double layer of the basal epithelium with limited growth capacity. The continuously growing incisor of the rodent is subdivided into a crown analog half on the labial side, with a cervical loop containing a large core of stellate reticulum, and its progeny gives rise to enamel producing. The lingual side is known as the root analog and gives rise to ERM. We show that the lingual cervical loop contains a small core of stellate reticulum cells and suggest that it acts as a functional stem cell niche. Similarly we show that continuously growing roots represented by the sloth molar and K14-Eda transgenic incisor maintain a cervical loop with a small core of stellate reticulum cells around the entire circumference of the tooth and do not form a HERS, and still give rise to ERM. We propose that HERS is not a necessary structure to initiate root formation. Moreover, we conclude that crown vs. root formation, i.e. the production of enamel vs. cementum, and the differentiation of the epithelial cells into ameloblasts vs. ERM, can be regulated independently from the regulation of stem cell maintenance. This developmental flexibility may underlie the developmental and evolutionary diversity in tooth patterning.

Epithelial Cell Rests of Malassez and OX6‐Immunopositive Cells in the Periodontal Ligament of Rat Molars: A Light and Transmission Electron Microscope Study

It has been shown that human and cat epithelial cell rests of Malassez (ERM) consist of heterogeneous cell populations. Immunohistochemical and immunoelectron microscopic analyses have verified the presence of neuroendocrine and Merkel-like cells in both of these epithelia. During experimental orthodontic tooth movement, immunocompetent cells have also been found in the vicinity of ERM in rat periodontal ligament (PDL), but have not been characterized in normal rat PDL. The aim of this study was to investigate the presence and distribution of MHC class II antigen presenting cells by using OX6 antibody in ERM of rat molars by light and transmission electron microscopy. Immunohistochemical and immunoelectron microscopic observations of rat maxillary molars confirmed the presence of OX6-positive cells in contact with ERM. Some immunopositive cytoplasmic processes containing vesicles interdigitated with cells of the Malassez epithelial clusters. Based on these findings it can be concluded that immunocompetent cells are localized close to Malassez epithelial clusters in normal rat PDL. Furthermore, the ultrastructural evidences indicate a possible interaction between the epithelial and immunocompent cells and suggest morphological and functional properties for ERM.

Craniopharyngioma

Craniopharyngiomas are benign slow growing tumours that are located within the sellar and para sellar region of the central nervous system. The point prevalence of this tumour is approximately 2/100,000. The onset of symptoms is normally insidious with most patients at diagnosis having neurological (headaches, visual disturbances) and endocrine (growth retardation, delayed puberty) dysfunctions. Craniopharyngiomas are thought to arise from epithelial remnants of the craniopharyngeal duct or Rathke's pouch (adamantinomatous type) or from metaplasia of squamous epithelial cell rests that are remnants of the part of the stomadeum that contributed to the buccal mucosa (squamous papillary type). The neuroradiological diagnosis is mainly based on the three components of the tumour (cystic, solid and calcified) in the characteristic sellar/para sellar location. Definitive diagnosis is made following histological examination of a surgical specimen. The differential diagnosis includes other tumours in this region (pituitary adenoma), infectious or inflammatory processes (eosinophilic granuloma), vascular malformations (aneurysm) and congenital anomalies (Rathke's cleft cyst). The current treatment is gross total excision of the tumour, if there is no hypothalamic invasion or, in the presence of hypothalamic invasion, a sub-total resection with post-operative radiotherapy. Endocrine disturbances are normally permanent and need careful replacement. Overall, there is an 80% 5 year survival, though this can be associated with marked morbidity (hypothalamic dysfunction, altered neuropsychological profile).

Proliferation of Epithelial Cell Rests, Formation of Apical Cysts, and Regression of Apical Cysts after Periapical Wound Healing

There is continuing controversy regarding the potential for inflammatory apical cysts to heal after nonsurgical endodontic therapy. Molecular cell biology may provide answers to a series of related questions. How are the epithelial cell rests of Malassez stimulated to proliferate? How are the apical cysts formed? How does the lining epithelium of apical cysts regress after endodontic therapy? Epithelial cell rests are induced to divide and proliferate by inflammatory mediators, proinflammatory cytokines, and growth factors released from host cells during periradicular inflammation. Quiescent epithelial cell rests can behave like restricted-potential stem cells if stimulated to proliferate. Formation of apical cysts is most likely caused by the merging of proliferating epithelial strands from all directions to form a three-dimensional ball mass. After endodontic therapy, epithelial cells in epithelial strands of periapical granulomas and the lining epithelium of apical cysts may stop proliferating because of a reduction in inflammatory mediators, proinflammatory cytokines, and growth factors. Epithelial cells will also regress because of activation of apoptosis or programmed cell death through deprivation of survival factors or by receiving death signals during periapical wound healing.

Morphology of Malassez's epithelial rest‐like cells in the cementum: transmission electron microscopy, immunohistochemical, and TdT‐mediated dUTP‐biotin nick end labeling studies

It is known that epithelial islands are embedded in the cementum during tooth root formation, but details of this process remain unknown. The purpose of this study was to investigate the dynamic characteristics of Malassez's epithelial rest cells in the cementum during tooth root formation in pigs in vivo. The first molars of 6-mo-old pigs were used in this study. Specimens were decalcified before being embedded in paraffin. Paraffin sections were investigated using TdT-mediated dUTP-biotin nick end labeling (TUNEL), immunohistochemical, and ultrastructural techniques. Malassez's epithelial rest cells were located close to the root surface at the apical one-third of the periodontal ligament, and epithelial clusters surrounded by distinct lamina cementia were sometimes observed in the cementum. TUNEL-positive cells were detected only in the cementum. Malassez's epithelial rest cells in the periodontal ligament were completely surrounded by basement membranes, but epithelial clusters in the cementum were only intermittently surrounded by such membranes. Cytokeratin-positive cells in the superstratum of the cementum were directly connected by cementocytes and by desmosome-like structures. However, organelles were scarce in the cytokeratin-positive cells in the substratum of the cementum, and the matrix of the cementum was deposited in the cells. These results suggest that the majority of the fragmented Hertwig's root sheath remains in the periodontal ligament and that some cells, which are connected to cementoblasts, are embedded in the cementum and progress to apoptosis.

The epithelial cell rests of Malassez – a role in periodontal regeneration?

This article reviews general aspects about the epithelial cell rests of Malassez (ERM). The historical and general morphological features of the ERM are briefly described. The embryological derivation of the ERM is presented as an important consideration in understanding the events associated with their origin and possible functional roles within the periodontal ligament. The ultrastructural description of the ERM is also included to complement the morphological characteristics which distinguish these cells as the unique epithelial element of the periodontal ligament. The unique ability of these cells to synthesize and secrete a number of proteins usually associated with cells of mesenchymal origin, rather than ectodermal origin, is discussed in light of their role in cementum repair and regeneration. Such considerations lead to our hypothesis that one of the functional roles of the ERM may lie not only their role in maintaining and contributing to the normal periodontal cellular elements and function but also contributing, in a significant manner, to periodontal regeneration.