Possible Therapeutic Effect of Ghrelin and exosomes derived from Mesenchymal stem cells on induced chronic pancreatitis of adult albino rats (Histological and Immunohistochemical Study) (original) (raw)
Related papers
Exosomes in the pathogenesis, diagnosis and treatment of pancreatic diseases
Exosomes (EXOs) are small vesicles (30-200 nm) of endocytic origin which are released by many different cell types into the extracellular space. They may play a key role in facilitating cell-cell communication, under both physiological and pathological conditions. EXOs contain a wide range of RNA molecules and proteins. Their specific molecular signatures make them promising candidates in early diagnosis and prognosis of pancreatic diseases. EXOs could also provide a new method to monitor treatment response in patients suffering from pancreatic cancer and other diseases of the pancreas. Additionally they may help to improve current treatments via personalized medicine approaches using them as therapeutic vehicles themselves.
Egyptian Journal of Histology
Background: Acute pancreatitis (AP) is a common inflammatory disorder of digestive system. Mesenchymal stem cells (MSCs) and Wheat germ oil (WGO) could improve AP through their anti-inflammatory and antioxidant effects. Objective: Evaluate and compare the possible therapeutic effects of Bone marrow derived Mesenchymal Stem Cells (BMSCs) versus WGO on AP. Materials and Methods: 47 adult male albino rats were divided into 4 groups. Control group I (no.=12). AP was induced in the remaining 35 rats by a single intra peritoneal (I.P) injection of L-arginine (250 mg/100g). 5 rats died within the 1st hour after AP induction, the rest were divided randomly into group II (AP group; no.=10) that received no treatment, group III (BMSCs group; no.=10) and group IV (WGO group; no.=10). One hour after AP induction, group III was injected I.P. by 1ml of PKH26 labeled BMSCs (1x106 cells/ml) and group IV received WGO in a dose of 3 ml/kg body weight by oral gavage every 24 h for 3 successive days. Blood samples were collected 24 hours and on the 4 th day after AP induction for biochemical assessment of serum amylase, lipase, interleukin-1β and interleukin-10. Then, animals were sacrificed and specimens from the pancreas were prepared for Hematoxylin and eosin (HandE) stain and immune-histochemical staining using inducible Nitric Oxide Synthase (iNOS) and insulin antibodies. Morphometric measurements using image analyzer were done. Results: Group II showed extensive pancreatic damage associated with increase in serum amylase, lipase and interleukin-1B levels and reduction in interleukin-10 level. A significant increase in the area % of iNOS immunostaining and non-significant change in insulin immunostaining were detected. On the other hand, BMSCs group and WGO group showed improvement in the biochemical, histological and immunohistochemical results with better results in BMSCs group. Conclusion: BMSCs possess better therapeutic efficacy in treating AP compared with WGO.
Exogenous Ghrelin Enhances Endocrine and Exocrine Regeneration in Pancreatectomized Rats
Journal of Gastrointestinal Surgery, 2009
Aim Ghrelin, the most important modulator of endocrine and exocrine pancreatic functions, has a role in the development of islets of Langerhans during embryogenesis. The aim of this study was to evaluate the effects of ghrelin on pancreatic regeneration in rats with 90% pancreatectomy. Materials and Methods Two- to 3-week-old Wistar rats were used in the study. After anesthesia, 90% pancreatectomy was performed. In the ghrelin group, 90% pancreatectomy was performed. Ten nanomoles per kilogram per day of ghrelin was administered intraperitoneally from the first postoperative day. In the antagonist group, 90% pancreatectomy was performed. From the first postoperative day, rats received the ghrelin receptor antagonists and substance P intraperitoneally at 1 μmol/kg. In the control group, 90% pancreatectomy was performed, and intraperitoneal saline was administered. The sham group did not receive pancreatectomy. Eight rats from each group were randomly selected and sacrificed on the second, third, and 30th days. Results Blood glucose levels in pacreatectomized rats were significantly higher than in rats in the sham group. The number of beta islet cells, serum insulin levels, and PDX-1 and cytokeratin staining scores decreased in rats with pancreatectomy when compared to the sham-group rats. In the ghrelin-receiving rats, blood glucose levels tended to decrease from the 15th postoperative day. Ghrelin treatment increased insulin levels, insulin-positive islet cell number, and 5-bromo-2-deoxyuridine and PDX-1 staining, whereas ghrelin antagonist administration resulted in significant decreases in these parameters. Ghrelin treatment significantly improved glucose tolerance test results. Conclusion Exogenous ghrelin administration decreased blood glucose levels after 90% pancreatectomy by increasing islet cell numbers and enhancing endocrine and exocrine regeneration.
The American Journal of Pathology, 2015
In this study, we aimed to evaluate the effects of exenatide (EXE) treatment on exocrine pancreas of nonhuman primates. To this end, 52 baboons (Papio hamadryas) underwent partial pancreatectomy, followed by continuous infusion of EXE or saline (SAL) for 14 weeks. Histological analysis, immunohistochemistry, Computer Assisted Stereology Toolbox morphometry, and immunofluorescence staining were performed at baseline and after treatment. The EXE treatment did not induce pancreatitis, parenchymal or periductal inflammatory cell accumulation, ductal hyperplasia, or dysplastic lesions/pancreatic intraepithelial neoplasia. At study end, Ki-67epositive (proliferating) acinar cell number did not change, compared with baseline, in either group. Ki-67epositive ductal cells increased after EXE treatment (P Z 0.04). However, the change in Ki-67epositive ductal cell number did not differ significantly between the EXE and SAL groups (P Z 0.13). M-30e positive (apoptotic) acinar and ductal cell number did not change after SAL or EXE treatment. No changes in ductal density and volume were observed after EXE or SAL. Interestingly, by triple-immunofluorescence staining, we detected c-kit (a marker of cell transdifferentiation) positive ductal cells co-expressing insulin in ducts only in the EXE group at study end, suggesting that EXE may promote the differentiation of ductal cells toward a b-cell phenotype. In conclusion, 14 weeks of EXE treatment did not exert any negative effect on exocrine pancreas, by inducing either pancreatic inflammation or hyperplasia/dysplasia in nonhuman primates.
The ghrelin pentapeptide inhibits the secretion of pancreatic juice in rats
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2006
Ghrelin, a 28 amino acids polypeptide was recognized as an endogenous ligand for the growth hormone secretagogue receptor. It turned out that the entire sequence of ghrelin is not necessary for performing the above-mentioned functions. It was suggested that 5 residues (Gly-Ser-Ser(n-octanoyl)-Phe, pentaghrelin) constituted functionally active part of the full-length polypeptide. Ghrelin-28 was found to inhibit pancreatic enzyme output in rats, though the effect of pentaghrelin was not studied so far. The study aimed to determine the involvement of pentaghrelin in pancreatic juice secretion in anaesthetized rats. Male Wistar rats (220 +/- 20 g body weight, b. wt.) were anesthetized, the external jugular vein and common biliary-pancreatic duct were cannulated. Pentaghrelin boluses (i.v., 1.2, 12, and 50 nmol kg(-1) b. wt.) were injected every 30 min with or without CCK-8 infusion, duodenal mucosal CCK(1) receptor blockade with tarazepide, vagotomy and capsaicin pretreatment. Pentaghre...
Role of mesenchymal stem cells and taurine in chronic pancreatitis in adult albino rats
European Journal of Anatomy
Chronic pancreatitis (CP) is an inflammatory disease of the pancreas that leads to pancreatic fibrosis. The current treatment of the disease is not efficient or adequate. Therefore, more efficient interventions are required to diminish the substantial burden of the disease. The present study aimed to assess the potential therapeutic value of bone marrow-derived mesenchymal stem cells (BMSCs) and/or taurine supplementation in CP-induced, using intraperitoneal injection of L-arginine. Forty-five rats were randomly divided into five groups (9 rats each): 1) control group, 2) CP group, 3) CP+BMSCs, 4) CP+Taurine, and 5) CP+BMSCs+Taurine. At the end of the experimental period, the pancreatic tissues were collected, weighed, and prepared for light, electron, and immunohistochemical (α-SMA) microscopic examination. The CP group showed destruction of the pancreatic tissues including fatty degeneration, minimal zymogen granules, and focal degranulation of the rER. Some of the islets degenera...
2020
Islet cell death and loss of function after isolation and before transplantation is considered a key barrier to successful islet transplantation outcomes. Mesenchymal stem cells (MSCs) have been used to protect isolated islets owing to their paracrine potential partially through the secretion of vascular endothelial growth factor (VEGF). The paracrine functions of MSCs are also mediated, at least in part, by the release of extracellular vesicles including exosomes. In the present study, we examined (i) the effect of exosomes from human MSCs on the survival and function of isolated mouse islets and (ii) whether exosomes contain VEGF and the potential impact of exosomal VEGF on the survival of mouse islets. Isolated mouse islets were cultured for three days with MSC-derived exosomes (MSC-Exo), MSCs, or MSC-conditioned media without exosomes (MSC-CM-without-Exo). We investigated the effects of the exosomes, MSCs, and conditioned media on islet viability, apoptosis and function. Besides...
Livestock Science, 2007
Ghrelin-28 was found to inhibit the pancreatic enzyme output in rats, although the effect of pentaghrelin has not been studied. The effect of ghrelin on pig exocrine pancreas remains largely unknown. The aim of the present study was: (1) to establish a model of porcine dispersed pancreatic acinar cells in vitro and compare it with an existing rat model, and (2) to investigate the effect of pentaghrelin on amylase release from the rat and pig pancreatic acini. The rat and porcine acinar cell preparations released amylase in response to cholecystokinin octapeptide (CCK-8) stimulation in a dose-related manner. Pentaghrelin hardly inhibited the amylase release in rat preparations (maximum inhibition with 10 − 9 M pentaghrelin). It stimulated amylase release in porcine preparations, however, no dose response was found in a range of doses between 10 − 10 and 10 − 7 M. Concluding, pentaghrelin may stimulate amylase release from porcine acinar cells through as yet unknown mechanisms.