The Therapeutic Potential of Extracellular Vesicles Versus Mesenchymal Stem Cells in Liver Damage

BACKGROUND@#The extracellular vesicles (EVs) secreted by bone marrow-derived mesenchymal stem cells (MSCs)hold significant potential as a novel alternative to whole-cell therapy. We herein compare the therapeutic potential of BMMSCsversus their EVs (MSC-EVs) in an experimental Carbon tetrachloride (CCl4)-induced liver damage rat model. @*METHODS@#Rats with liver damage received a single IV injection of MSC-EVs, 1 million MSCs, or 3 million MSCs. Thetherapeutic efficacy of each treatment was assessed using liver histopathology, liver function tests and immunohistochemistryfor liver fibrosis and hepatocellular injury. @*RESULTS@#Animals that received an injection of either MSCs-EVs or 3 million MSCs depicted significant regression ofcollagen deposition in the liver tissue and marked attenuation of hepatocellular damage, both structurally and functionally. @*CONCLUSION@#Similar to high doses of MSC-based therapy (3 million MSCs), MSC-EVs mitigated the fibrogenesis andhepatocellular injury in a rat model of CCl4-induced liver fibrosis. The anti-fibrinogenic effect was induced by attenuatinghepatic stellate cell activation. Therefore, the administration of MSC-EVs could be considered as a candidate cell-freetherapeutic strategy for liver fibrosis and hepatocellular damage.

The Therapeutic Potential of Extracellular Vesicles Versus Mesenchymal Stem Cells in Liver Damage

BACKGROUND@#The extracellular vesicles (EVs) secreted by bone marrow-derived mesenchymal stem cells (MSCs)hold significant potential as a novel alternative to whole-cell therapy. We herein compare the therapeutic potential of BMMSCsversus their EVs (MSC-EVs) in an experimental Carbon tetrachloride (CCl4)-induced liver damage rat model. @*METHODS@#Rats with liver damage received a single IV injection of MSC-EVs, 1 million MSCs, or 3 million MSCs. Thetherapeutic efficacy of each treatment was assessed using liver histopathology, liver function tests and immunohistochemistryfor liver fibrosis and hepatocellular injury. @*RESULTS@#Animals that received an injection of either MSCs-EVs or 3 million MSCs depicted significant regression ofcollagen deposition in the liver tissue and marked attenuation of hepatocellular damage, both structurally and functionally. @*CONCLUSION@#Similar to high doses of MSC-based therapy (3 million MSCs), MSC-EVs mitigated the fibrogenesis andhepatocellular injury in a rat model of CCl4-induced liver fibrosis. The anti-fibrinogenic effect was induced by attenuatinghepatic stellate cell activation. Therefore, the administration of MSC-EVs could be considered as a candidate cell-freetherapeutic strategy for liver fibrosis and hepatocellular damage.

Effect of dietary arginine on the jejunal mucosa in indomethacin-induced intestinal injury: light and scanning electron microscopic study in male mice

The non-steroidal anti-inflammatory drug [NSAID] indomethacin causes, via its adverse effects, damage to the gastrointestinal mucosa of humans and experimental animals. The indomethacin-induced intestinal injury in mice jejunum is considered an experimental model of Crohn's disease, as one of the inflammatory bowel diseases [IBD's]. The semi-essential amino acid arginine, which is a precursor of nitric oxide, is proposed to promote gastrointestinal mucosal integrity. The present work aimed to study the possible protective role of dietary supplementation with arginine in ameliorating indomethacin-induced mucosal injury of mice jejunum. The present study was carried out on forty adult male mice which were divided into 4 equal groups; group I [negative control group] which received no treatment, group II [positive control]; mice received dietary L-arginine alone in a daily dose of 300 mg/Kg, group III [indomethacin group]; mice of this group received 2 consecutive subcutaneous injections of indomethacin in a dose of 7.5 mg/kg, 24 hours apart and group IV [arginine group]; in which arginine supplementation was provided 2 days before the administration of indomethacin, maintained during the administration and continued 3 days later till the end of the experiment. Mice of all groups were sacrificed by the end of the 7[th] day and specimens from the jejunum were dissected and processed for light and scanning electron microscopic examinations. Indomethacin-treated group exhibited jejunal mucosal injury. Light microscopic examination of this group, using H and E and toluidine blue- stained semithin sections showed distorted villi and sloughing of some of their apical parts with extrusion of many degenerated cells, intermingled with excess mucous. Some enterocytes appeared degenerated with loss of their regular arrangement, while the goblet cells appeared distended with excess mucous secretion. Increased cellular infiltration and edema of the villous core and in the lamina propria between the glands were noticed. Increased mucous secretion was also demonstrated by combined alcian blue-periodic acid Schiff reaction. Scanning electron microscope revealed alteration in the architecture of many villi which appeared short, blunt or with denuded surface and occasionally covered with membrane-like structure. The group of mice received arginine [group IV] revealed restoration of mucosal integrity in the form of regular villi with intact epithelial coverings including enterocytes and goblet cells. Some villi appeared shorter, while others showed partially denuded apical surface. Arginine evoked a remarkable cellular infiltration. Lymphocytes and macrophages were among the infiltrating cells and their roles were suggested to be vital in the healing process. Dietary L-arginine provided satisfactory protection against indomethacin-induced mucosal injury in mice, most probably via its role as a nitric oxide donor. So supplementation with dietary arginine is recommended

new anti-rheumatic drug leflunomide [Avara] and the associated risk of pulmonary toxicity: a histological study on the alveoli of albino rats

Leflunomide [Avara] is a novel drug for the treatment of active rheumatoid arthritis. The controversy about the associated risk of respiratory infection in patients treated with leflunomide was the main drive for the present study. The present study aimed to demonstrate the histological changes that might occur in the alveolar structure of the lung in rats treated with leflunomide for 4 weeks and to investigate the effect of stoppage of drug administration for another 2 weeks. The present work was conducted on 30 adult male albino rats which were divided into 3 equal groups; group I [control group], group II [leflunomide treated group] which received leflunomide in an oral dose of 10mg/kg for 4 weeks. Group III [withdrawal group] the rats received the leflunomide treatment in a similar way to group II, then they were kept without treatment for another 2 weeks to test for possible spontaneous recovery. By the end of the experimental period, the animals were sacrificed and specimens from the lungs were taken, processed and examined by light and transmission electron microscopes. Examination of leflunomide treated group revealed marked alteration in the histological structure, as many alveoli appeared collapsed with evident thickening of the inter-alveolar septa which showed cellular infiltration and congested blood capillaries. Some red blood cells were seen extravasated in the alveolar spaces. Hyperplasia ofpneumocyte type II which appeared with empty lamellar bodies and pyknotic nuclei were depicted. Stoppage of drug administration for 2 weeks after treatment, did not succeed in restoration of the normal histological structure of the alveoli. On the contrary, severe cellular infiltration of the inter-alveolar septa were observed in the withdrawal group. The alveolar air spaces were seen obliterated surrounded with many pneumocytes type II which showed morphological changes including enlarged cells with swollen mitochondria. Plasma cells, lymphocytes, eosinophils, many degenerated ill-defined cells, multiple fibroblasts and excess collagen were seen. Trichrome stain also revealed excess collagen deposition in both leflunomide treated group and in the withdrawal group. The present results revealed that leflunomide induced lung toxicity with evident histological changes in the alveoli which mimicked that of interstitial pneumonitis. On the other hand, discontinuation of the drug for another 2 weeks did not succeed in spontaneous recovery or amelioration of these changes, most probably through its pharmacokinetics as regards the long half life of elimination of the drug and the increased risk of opportunistic infection

Histological changes in the filiform and fungiform lingual papillae of streptozotocin-induced diabetic albino rats and the possible protective role of curcumin

It has been a growing interest recently in dietary intervention, particularly the use of traditional food derived from natural sources in management of diabetic complications as oral lesions. The aim of the present study was to elucidate the histological changes in the lingual papillae in an experimental model of induced diabetes in rats by streptozotocin and evaluate the possible protective effect of curcumin using light and scanning electron microscopes. Thirty adult male albino rats were divided into 3 equal groups: group 1; [control group], group II;[diabetic group]: diabetes was induced by a single intraperitoneal injection of streptozotocin in a dose of 65 mg/kg and group [Unprotected group] rats were treated as in diabetic group with simultaneous administration of' curcumin in a daily dietary dose of 15 mg/kg for 4 weeks. By the end of the 4 weeks all animals were sacrificed and the tongues of all rats were dissected and processed for light and scanning electron microscopic examination. Examination of dorsal surface of tongues of diabetic rats revealed numerous filiform papillae with evidently disturbed shape and orientation. Some of them depicted notched or bifurcated ends; others were severely destroyed with desquamation of their epithelial covering. There were hyperkeratosis and markedly reduced connective tissue papillae. Disfigured fungiform papillae with vacuolated taste buds depicting peripheral arrangement of the cells and empty center were also seen. Dorsal surface rats' tongues of the protected group with curcumin revealed almost normal direction, distribution and structure of the papillae except for few filiform papillae with serrated tips. The present study illustrated that diabetes has a deleterious effect on tongue papillae and taste buds. On the other hand, curcumin provided considerable protection against these effects most probably via its antioxidant, anti-inflammatory and neuroprotective effects

Histological study of the possible toxic effect of selenium on the thyroid follicular cells of albino rats

Selenium is a trace element, essential in small amounts, but it can be toxic in larger amounts. Selenium compounds are widely used as a dietary supplement and as a prophylaxis for the prevention of cancer, cardiovascular diseases and viral mutations. However, there is a narrow margin between safe therapeutic and toxic doses of selenium. The goal of the present study was to study the histological effect of the adequate and toxic doses of selenium on the follicular cells of thyroid gland of albino rats. The study was carried out on 30 adult male albino rats weighing 120-150 gm. Animals were divided into 3 equal groups: Control group; which received adequate diet but without the addition of selenium. Group I [supplemented group]: received sodium selenite in a dose of 75 microgram / kg b.w., and group II [Intoxicated group]: received sodium selenite in a dose of 300 microgram /kg bw. Histological examination of the semithin and ultrathin sections of the supplemented group [group I] revealed nearly normal control image in most of the examined thyroid follicles. Few follicles showed some follicular cells with vacuolated cytoplasm and many dense bodies and others showed irregular nuclei. Ultrastructural examination revealed some cells with dilated cisternae of rough endoplasmic reticulum, widened intercellular spaces and the infiltration of the interstitial spaces with some inflammatory cells and excessive collagen deposition. Histological examination of the intoxicated group [group II] revealed hypertrophy and hyperplasia of the thyroid follicles which appeared crowded with minimal interfollicular spaces. Some follicles showed stratification of their lining cells while others showed dome shaped cells with vacuolated cytoplasm and many dense bodies. Numerous basal and lateral cytoplasmic processes, interrupted epithelial lining and exfoliated cells in the lumina were frequently encountered. The present work recommend the intake of natural diet enriched with high content of selenium and warn about daily intake of exceeding doses of selenium supplementations

Study of efficacy of intravitreal injection of ciprofloxacin versus vancomycin and ceftazidime in treating experimental endophthalmitis

Endophthalmitis is a severe inflammation of the interior of the eye caused by the introduction of contaminating microorganisms. The aim of this study was to compare the efficacy of intravitreal injection of vancomycin and ceftazidime versus ciprofloxacin in an experimental model of Staph. Epidermidis induced endophthalmitis in rabbits. The study was conducted on the right eyes of 35 pigmented rabbits, 5 of which were used as control group. All remaining 30 eyes were inoculated with 3 x 10[6] CFU / 0.1 ml of Staph. epidermidis then, they were divided into 3 equal groups. 24 hours postinoculation, group I: was given no treatment, group II received a combined intravitreal injection of vancomycin [1 mg /0.1 ml] and ceftazidime [2.25 mg / 0.1 ml], and group III received an intravitreal injection of ciprofloxacin [100 micro g/ 0.1 ml]. From each group, 72 hours postinoculation, 5 rabbits were used for clinical examination and then they were sacrificed, their right eyes were enucleated, and vitreous colony count was done. The other 5 rabbits were also sacrificed, their right eyes were enucleated, and histologlcal examination by LM and TEM was performed. The clinical examination revealed that the conjunctival injection and the corneal oedema were significantly less in group II in comparison to group I and III. The bacterial colony count was markedly decreased in group II in comparison to group I and III with a significant difference. Histological examination by LM and TEM revealed that the endophthalmitis group [group I] showed complete loss of architecture of the retina and choroid with disruption of the Bruch's membrane. Multiple degenerated cells and red blood cells were seen infiltrating the degenerated retina. On the contrary, the retinal structure was preserved to a great extent in group II, [vancomycin and ceftazidime group] except for focal areas of disorganization in the photoreceptor layer and mild invasion by inflammatory cells. Eyes treated with ciprofloxacin showed degeneration of the pigmented epithelial cells and the photoreceptor cell layers, pyknosis and karyolysis of the outer nuclear layer and infiltration of the all retinal layers with mononuclear cellular infiltration. Intravitreal injection of vancomycin [1 mg / 0.1 ml] and ceftazidime [2.25 mg / 0.1 ml] was more effective than ciprofloxacin [100 micro g / 0.1 ml] in improving the clinical signs, decreasing the bacterial colony count, and preserving the retinal structure in Staph. epidermidis endophthalmitis

Histological changes in the alveolar structure of the rat lung after exposure to hyperoxia

The study evaluated the effect of acute and subchronic exposure to normobaric hyperphysiologic concentrations of oxygen [O2] on the alveolar structure of rat lung. This study was carried out on thirty adult male albino rats divided equally into 5 groups. Group I: included unexposed rats, to be considered as control group, group II; included rats exposed to 95% O2 for 24 hours, group III rats were exposed as in group II and were left for recovery in room air for 2 weeks. Group IV: included rats exposed to 60% 02 for two weeks, group rats were exposed as in group IV, then left in room air for another two weeks. The alveolar structure of the rat lung for all groups was examined by light and transmission electron microscopy. The present work demonstrated that exposure to 95% 02 for 24 hours resulted in severe pulmonary congestion with extravasation of red blood cells, edema and alteration in alveolar structure, while recovery in room air for another 2 weeks did not result in repair of the alveolar structure. On the other hand, exposure to 60% O2 for 2 weeks resulted in focal affection of the alveoli with thickened inter-alveolar septum, intense cellular infiltration together with proliferation of type II pneumocyte and deposition of interstitial collagen fibers, while recovery in room air for another 2 weeks was associated with partial improvement in alveolar structure

role of streptokinase in induction of posterior vitreous detachment: a scanning and transmission electron microscopic study of the retina in rabbits

The study was conducted to evaluate the possibility of inducing posterior vitreous detachment [PVD] by intravitreal injection of Streptokinase using scanning and transmission electron microscopic, and electrophysiological study. The present study was performed on thirty eyes of fifteen male white rabbits. The rabbits were divided into three equal groups. The right eye of the 3 groups received intravitreal injection of Streptokinase at three different concentrations [150,1500 and 15000 IV in 0.1 mL balanced salt solution [BSS]] in the- midvitreous cavity. The left eye in all animals received intravitreal injection of BSS and were considered as control group. Electroretinograph [ERG] was performed one hour, one day and one week following injection. The rabbits were killed after ten days and the enucleated eyes were processed for transmission and scanning electron microscopic examination. In group I, scanning electron microscopy showed the retinal surface covered with thin collagen fibers, while in group II, complete PVD with bare retinal surface was seen. Group III showed a bare retinal surface with hemorrhagic reaction and toxic effects on the retina by transmission electron microscopy. ERG findings are discussed. Intravitreal injection of 1500 IU of Streptokinase can lead to PVD without major toxic effects on the retina