The Immunomodulatory Potential Role of Mesenchymal Stem Cells in Diseases of the Central Nervous System.

INTRODUCTION: Several studies indicate the role of mesenchymal stem cells (MSCs) as an important tool in regenerative medicine associated with injuries that affect the central nervous system (CNS). The MSCs have the capacity to differentiate into cells of the embryonic tissue, such as the mesoderm. So, these cells can be found in a variety of tissues. Also, the MSCs can release immunomodulatory and neurotrophic factors performance as inflammation mediators operating in injured tissue regeneration. Furthermore, they can differentiate into neural-like cells in vitro. Thereby, because of the high immunomodulatory role of MSCs, this review sought to describe the main immunomodulatory mechanisms performed by MSCs in CNS recovery after tissue injury or neurodegenerative diseases. METHODS: PubMed and ScienceDirect were searched between January 2011 to March 2021, and 43 articles met the criteria of the review. RESULTS: This systematic review indicates that MSCs were used in vivo experimental multiple sclerosis, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, ischemic stroke, and traumatic brain injury. The treatment MSCs were usually from human origin, derived from bone marrow, and administered intravenously. CONCLUSION: It was shown that MSCs, independent from origin or administration pathway, can reduce inflammation and help in the recovery and preservation of injured neural tissue. Thus, the use of MSCs represents a potential therapeutic option in the treatment of neurological disorders mediated by inflammatory processes.

Rat Facial Nerve Regeneration with Human Immature Dental Pulp Stem Cells.

Facial paralysis can result in severe implications for the patients. However, stem cell biology has become an important field in regenerative medicine since the discovery and characterization of mesenchymal stem cells. Our aim was to evaluate the regeneration after facial nerve crush injury and application of human immature dental pulp stem cells (iDPSC). For this study 70 Wistar rats underwent a unilateral facial nerve crush injury and were divided into two groups: Group I (GI): Crushed; Group II (GII): Crushed and iDPSC, and distributed into study periods of 3, 7, 14, 21, and 42 postoperative days. Facial nerve regeneration was analyzed via functional recovery of whisker movement, histomorphometric analysis, and immunoblotting assay. The results show that GII had complete functional recovery at 14 days, while GI recovered after 42 days. Also, regarding the facial nerve trunk, GII presented histological improvement, evidencing better axonal and structural organization of the myelin sheath, and exhibited statistically higher values for the outer and inner perimeters and g-ratio. Nevertheless, GI exhibited statistically higher values for the thickness of myelin sheath. In the buccal branch, no differences were observed for all parameters between groups. At 42 days, both groups GI and GII were close to the levels observed for the control group. Concerning nerve growth factor expression, GII exhibited statistically greater values (p < 0.05) compared with the control group at 7 days. In summary, a single injection of human iDPSC promoted a positive effect on regeneration of the facial nerve trunk after 14 days and provided an alternative to support regeneration following peripheral nerve injury.

Effect of Laser Photobiomodulation with Gradual or Constant Doses in the Regeneration of Rats' Mental Nerve After Lesion by Compression.

OBJECTIVE: Assess morphologically the efficacy of constant dose (CD) or gradual dose (GD) in photobiomodulation therapy (PBMT) during the regeneration process of rats' mental nerve after compression lesion. MATERIALS AND METHODS: Forty-eight male Wistar rats were used and divided into four groups (n = 12): negative control (NC): lesion by compression; positive control (PC): no lesion; GD: lesion by compression and PBMT with GD; and CD: lesion by compression and PBMT with CD. One day after the surgery, the groups GD and CD underwent PBMT daily in three equidistant points around the incision area. The parameters were wavelength of 808 nm, 100 mW, CD received treatment with 120 J/cm2, while GD underwent the protocol of application: 1st and 4th sessions: 80 J/cm2; 5th to 8th sessions: 90 J/cm2; 9th to 12th sessions: 100 J/cm2; 13th to 16th sessions: 110 J/cm2; and 17th to 20th sessions: 120 J/cm2. Euthanasias were performed at 3, 7, 14, and 21 days. Qualitative and quantitative analysis of the mental nerves were performed with ANOVA (analysis of variance) and Tukey tests (p ≤ 0.05). RESULTS: It was observed that PBMT was able to accelerate the process of nerve regeneration presenting an increase in the number of myelinated fibers starting at 14 days of treatment for groups CD and GD, and at 21 days they were similar to PC. It was observed a better lamellar organization of myelin sheath at 7 days for GD and at 14 days for CD, similar to PC. Both GD and CD presented significant differences compared to NC and PC for thickness of the myelin sheath, outer perimeter, internal area, and number of myelin fibers. CONCLUSIONS: PBMT presented positive effect on the regeneration of nerve starting at 14 days, and after 21 days there was no difference between GD and CD.

Stem Cells from Human Exfoliated Deciduous Teeth: A Growing Literature.

Adult stem cells research has been considered the most advanced sort of medical-scientific research, particularly stem cells from human exfoliated deciduous teeth (SHED), which represent an immature stem cell population. The purpose of this review is to describe the current knowledge concerning SHED from full-text scientific publications from 2003 to 2015, available in English language and based on the keyword and/or abbreviations 'stem cells from human exfoliated deciduous teeth (SHED)', and individually presented as to the properties of SHED, immunomodulatory properties of SHED and stem cell banking. In summary, these cell populations are easily accessible by noninvasive procedures and can be isolated, cultured and expanded in vitro, successfully differentiated in vitro and in vivo into odontoblasts, osteoblasts, chondrocytes, adipocytes and neural cells, and present low immune reactions or rejection following SHED transplantation. Furthermore, SHED are able to remain undifferentiated and stable after long-term cryopreservation. In conclusion, the high proliferative capacity, easy access, multilineage differentiation capacity, noninvasiveness and few ethical concerns make stem cells from human exfoliated deciduous teeth the most valuable source of stem cells for tissue engineering and cell-based regenerative medicine therapies.

Pluripotent stem cell transcription factors during human odontogenesis.

Stem cells are capable of generating various cell lines and can be obtained from adult or embryonic tissues for clinical therapies. Stem cells from deciduous dental pulp are among those that are easily obtainable from adult tissues and have been widely studied because of their ability to differentiate into a variety of cell lines in the presence of various chemical mediators. We have analyze the expression of several proteins related to the differentiation and proliferative potential of cell populations that compose the tooth germ of human fetuses. We evaluate 20 human fetuses of both genders. After being paraffin-embedded, cap and bell stages of tooth germ development were subjected to immunohistochemistry for the following markers: Oct-4, Nanog, Stat-3 and Sox-2. The studied antibodies showed nuclear or cytoplasmic immunnostaining within various anatomical structures and with various degrees of expression, indicating the action of these proteins during tooth development. We conclude that the interrelationship between these transcription factors is complex and associated with self-renewal and cell differentiation. Our results suggest that the expression of Oct-4, Nanog, Sox-2 and Stat-3 are related to differentiation in ameloblasts and odontoblasts.

Structural and ultrastructural features of the agouti tongue (Dasyprocta aguti Linnaeus, 1766).

The agouti (Dasyprocta aguti Linnaeus, 1766) is a wild rodent belonging to the family Dasyproctidae that is found throughout Brazil and feeds on fruits and seeds. The aim of the present study was to describe the following features of the tongue of agouti: its morphological structures, the three-dimensional characteristics of the lingual papillae surface, the connective tissue cores (CTCs) and the epithelial cell ultrastructure. Four types of papillae were observed on the dorsal surface of the tongue with a triangular shape: filiform, fungiform, foliate and vallate. Filiform papillae were distributed throughout the tongue surface, and removal of the epithelial surface revealed conical CTCs and multifilaments. Fungiform papillae were observed in the rostral and middle regions, whereas foliate papillae developed in pairs on the lateral margin of the caudal region. Removal of the epithelium in these regions revealed CTCs with parallel laminar conformation. Vallate papillae were arranged in a V-shape in the caudal region, and their CTCs ranged in shape from elongate to ovoid. The ultrastructural components of the dorsal epithelium were the basal, spinous, granular and keratinised layers. A broad area with cytoplasmic projections was identified in the interface region between the lamina propria and the basal layer. Flattened cells with intermediate filaments were observed in the transitional region between spinous and granular layers. The keratinised layer was composed of superimposed epithelial cells where desmosomes and cell-surface microridges were observed. These structural features, including the three-dimensional aspects of the lingual papillae, the CTCs and the epithelial ultrastructure, indicate that when compared with other animals, particularly other rodent species, the morphological features of the tongue of agouti are relatively well developed, especially regarding foliate and vallate papillae.

Structural characterization of the capybara (Hydrochaeris hydrochaeris) tongue by light, scanning, and transmission electron microscopy.

Capybara is the largest rodent in the world and displays a seasonally dependent herbivore feeding behavior. Here, we present an anatomical contribution for understand this fact, by light, scanning, and transmission electron microscopy methodologies for tongue tissue analysis. The histological preparations revealed filiform, fungiform, vallate, and foliate papillae on the dorsal mucosa of the capybara tongue. The epithelial layer exhibited a lining of keratinized stratified squamous epithelial cells. The lamina propria was characterized by a dense connective tissue composed of the primary and secondary papillar projections. We also revealed the original aspects of the connective papillae. The shapes of the papillae varied by region of the tongue, and filiform, fungiform, vallate, and foliate papillae and subjacent layers of muscular fibers were observed. Pyriform taste buds occupying the epithelial layer of fungiform, vallate and foliate papillae were identified and the intracellular components of the taste buds and the intracorpuscular amyelinated nerve fibers were observed. The taste buds were characterized by the distribution of granular endoplasmic reticulum throughout the perinuclear area, the Golgi apparatus, and mitochondrial assemblies of various distinct diameters. Mitochondrial accumulation was also observed in the collagen bundle-surrounded amyelinated nerve fibers beside the basal cells. Therefore, these peculiar anatomical descriptions may contribute to understanding the adaptation of the feeding behavior of capybaras in a seasonally changing environment.

Morphometric, quantitative, and three-dimensional analysis of the heart muscle fibers of old rats: transmission electron microscopy and high-resolution scanning electron microscopy methods.

This research investigated the morphological, morphometric, and ultrastructural cardiomyocyte characteristics of male Wistar rats at 18 months of age. The animals were euthanized using an overdose of anesthesia (ketamine and xylazine, 150/10 mg/kg) and perfused transcardially, after which samples were collected for light microscopy, transmission electron microscopy, and high-resolution scanning electron microscopy. The results showed that cardiomyocyte arrangement was disposed parallel between the mitochondria and the A-, I-, and H-bands and their M- and Z-lines from the sarcomere. The sarcomere junction areas had intercalated disks, a specific structure of heart muscle. The ultrastructural analysis revealed several mitochondria of various sizes and shapes intermingled between the blood capillaries and their endothelial cells; some red cells inside vessels are noted. The muscle cell sarcolemma could be observed associated with the described structures. The cardiomyocytes of old rats presented an average sarcomere length of 2.071 ± 0.09 µm, a mitochondrial volume density (Vv) of 0.3383, a mitochondrial average area of 0.537 ± 0.278 µm(2), a mitochondrial average length of 1.024 ± 0.352 µm, an average mitochondrial cristae thickness of 0.038 ± 0.09 µm and a ratio of mitochondrial greater length/lesser length of 1.929 ± 0.965. Of the observed mitochondrial shapes, 23.4% were rounded, 45.3% were elongated, and 31.1% had irregular profiles. In this study, we analyzed the morphology and morphometry of cardiomyocytes in old rats, focusing on mitochondria. These data are important for researchers who focus the changes in cardiac tissue, especially changes owing to pathologies and drug administration that may or may not be correlated with aging.

Qualitative study of young, adult, and aged Wistar rats temporomandibular synovial membrane employing light, scanning, and transmission electron microscopy.

The aim of this study was to analyze the rat temporomandibular joint (TMJ) synovial membrane at different ages using light, scanning, and transmission electron microscopy. Under light microscopic analysis, the TMJ structures were observed such as condyle, capsule, disk, the synovial membrane collagen type, and cells distribution. In the scanning electron microscopy, the synovial membrane surface exhibited a smooth aspect in young animals and there was an increase with ageing in the number of folds. The transmission electron microscopic analysis showed more synoviocytes in the synovial layer in the young group and still a great number of vesicles and cisterns dilation of rough endoplasmic reticulum in the aged group. In the three groups, a dense layer of collagen fibers in the synovial layer and cytoplasmic extensions were clearly seen. It was possible to conclude that synovial membrane structures in aged group showed alterations contributing to the decrease in joint lubrication and in the sliding between disk and joint surfaces. These characteristic will reflect in biomechanics of chewing, and may cause the TMJ disorders, currently observed in clinical processes.

Ultrastructural aspects of female aging Wistar rat epithelium tongue: a HRSEM and TEM study.

BACKGROUND: There is general consensus that the effects of intrinsic aging on the oral mucosa are relatively small, though potentially important to understanding the pathologies present in the aged animals. OBJECTIVE: In this paper, the development of dorsal surface of rat tongue was examined using transmission electron microscopy (TEM) and high-resolution scanning electron microscopy (HRSEM) in order to understand the age-related structural and ultrastructural changes experimentally. METHODS: In this study, we used female rats 75 and 720 days old (adult and aging). Tissues of rat tongue were prepared and the specimens submitted to HRSEM and TEM techniques. RESULTS: The analysis of HRSEM and TEM demonstrated that the same characteristic keratinous epithelium was found in aging animals, however with some modifications. CONCLUSION: We agree that there are obvious changes in the oral mucosa with aging and these modifications can be observed starting from the ultrastructural aspects.

Allogenous bone grafts improved by bone marrow stem cells and platelet growth factors: clinical case reports.

In order to increase the amount of available bone where dental implants must be placed, the present study has associated platelet-rich plasma (PRP) and mononuclear cells (MNCs) from bone marrow aspirate and bone scaffold (BS) in 32 patients aged between 45 and 75 years old. The MNC attainment and the adherence to the BS were confirmed through histology, cell culture, and scanning electron microscopy. The clinical results, analyzed by computed tomography, have showed that the scaffolds were well integrated and adapted to the cortical bone. We can conclude that the process of healing observed in the patients was due to the presence of mesenchymal stem cell in MNC fraction in the bone grafts.

Ultrastructure of the adhesion of bacteria to the epithelial cell membrane of three-day postnatal rat tongue mucosa: a transmission and high-resolution scanning electron microscopic study.

Togue mucosa surface of 3-day postnatal rats was examined under transmission electron microscopy (TEM) and high-resolution scanning electron microscopy (HRSEM). For HRSEM analysis, the specimens were fixed in the same solution for 24 h, postfixed in 2% osmiun tetroxide, critical-point dried and coated with platinum-palladium. For TEM analysis, the specimens were fixed using modified Karnovsky solution and embedded in Spurr resin. The results revealed the presence of numerous microplicae in the membrane surface of keratinized epithelial cells to which groups of bacteria were attached. These bacteria were staphylococcus and coccus organized either in rows or at random, which were visualized in three-dimensional HRSEM images. At high magnification, the TEM images revealed the adhesion of bacteria to the cell membrane through numerous filamentous structures comprising the glycocalyx. The fine fibrillar structures rising from each bacterium and from cell membrane were clearly seen. These characteristics on bacteria structure may be used for future control or prevention of bacterial diseases and for installation of the oral native flora.

Angioarchitecture of the anterior and medium parts of the palatine mucosa of the gerbil, Meriones unguiculatus.

The aim of this study was to examine the microvasculature of the anterior and medium portions of the hard palatine mucosa in the adult gerbil (Meriones unguiculatus) using scanning electron microscopy. The vascular corrosion casts were obtained by injection of Mercox CL-2B synthetic resin and tissue corrosion was performed using sodium hydroxide solution. These casts revealed the presence of capillary loops in the palatine plicae and a smoother/flatter vascular network in the interplicae areas. The capillary loops consisted mainly of anteriorly oriented hair-pins and we also verified a differentiation in the shape of endothelial cell nuclei, which were elongated in arterial and circular in venous vessels.

Morphometric and High Resolution Scanning Electron Microscopy Study of Calomys callosus Major Palatine Nerve / Estudio Morfométrico y Electrónico de Barrido de Alta Resolución del Nervio Palatino Mayor del Calomys callosus

The characteristics of Calomys callosus major palatine nerve were studied employing light, transmission and high resolution scanning electron microscopy methods. For light microscopy, the specimens were fixed in Bouin's fixative solution, processed routinely and the sections were stained with hematoxylin­eosin and Azo-Carmin to identify nerve fibers. For high resolution scanning electron microscopy the O-D-O method reported by Tanaka (1989) was used to examine nerve fiber components and to measure the myelin sheath. Thin sections were examined by transmission electron microscopy to show axoplasmic elements and adjacent structures. The results revealed nerve fiber bundles in the lamina propria of Calomys callosus palatine mucosa. Nerve fibers were enveloped by cytoplasmic lamellae of perineural cells and adjacent collagen bundles, their diameter ranged from 1 to 6 µm, and the myelin sheath ranged from 0.2 to 0.9 µm. In the nerve fibers axoplasm were seen neurofilaments, mitochondria, neurotubules and few unmyelinated fibers.

Se estudiaron las características del nervio palatino mayor del Calomys callosus, utilizando métodos de microscopía luz y electrónica de transmisión y de barrido de alta resolución. En el caso de microscopía de luz las muestras se fijaron con solución fijadora de Bouin, se trabajaron de la forma habitual y las secciones se tiñeron con hematoxilina-eosina y con azo-carmín para identificar las fibras nerviosas. En el caso de microscopía electrónica de alta resolución se utilizó el método O-D-O indicado por Tanaka (1989) para examinar los componentes de la fibra nerviosa y medir la vaina de mielina. Se examinaron secciones finas usando microscopio electrónico de transmisión para poner en evidencia los elementos axoplásmicos y las estructuras adyacentes. Los resultados demuestran la presencia de uniones de la fibra nerviosa en la lámina palatina de la mucosa de Calomys callosus. Las fibras nerviosas están envueltas en lamelas citoplasmáticas de células perineurales y uniones de colágeno adyacente y su diámetro varía de 1 a 6µm; la vaina de mielina varía de 0.2 a 0.9 µm. En el axoplasma de las fibras nerviosas se observaron neurofilamentos, mitocondrias y neurotúbulos y se encontraron unas pocas fibras sin mielina.

Fine structure of the 7 postnatal days Calomys callosus palatine salivary glands.

The aim of this study has been to determine the ultrastructural characteristics of the minor palatine salivary glands on the seventh day of development and to demonstrate wether their secretion is mucous, serous or seromucous by light, transmission and scanning electron microscopy. This study has shown that the palatine gland acinar cells are predominantly mucous with some serous units. These cells contain electron dense (serous) and low electron dense (mucous) granules in the apical portions. The cytoplasmatic organelles like mitochondria, Golgi apparatus and rough endoplasmic reticulum are localized in a supranuclear portion. We could also observe the flattened myoepithelial cells surrounding the basal part of the acini with myofilaments, Golgi apparatus and mitochondria. Desmosomal junctions and membrane interdigitations are present between the acinar and the myoepithelial cells. A basal lamina, divided in two layers, an electron dense and an electron lucent is present between the glandular stroma which is composed of dense connective tissue and the endpieces.

Palatine mucosa angioarchitecture study of young rabbits using scanning electron microscopy

Pocos trabajos han relatado la angioarquitectura de animales jóvenes. Este estudio contribuye con las investigaciones acerca de la distribución tridimensional de la mucosa palatina en conejos jóvenes usando MEB. La corrosión vascular del molde fue obtenida usando resina de baja densidad-Mercox© CL-2B. No pudimos observar redes específicas en la cúpula de los pliegues palatinos, en los interpliegues y mucosa labial. Fueron observados solamente loops capilares y pliegues transversos palatinos