For this reason, more MSCs aggregates would form for IP route and produce higher level of serum TSG-6 under TNF- activation, which help reducing the colon inflammation. Article [4] In 1964, a study delivered chemical agents such as acetic acid, bradykinin, and kaolin to mice intraperitoneally in order to study a "squirming" response. Intraperitoneal Injection. Clipboard, Search History, and several other advanced features are temporarily unavailable. 4D,E). Your peritoneal (payr-ih-toh-NEE-ul) space is the area between the muscles and organs in your abdomen (belly). Further study demonstrated TSG-6 alone was sufficient to reduce intestinal inflammation in mice with colitis. Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Yuanmingyuan West Road No. PubMedGoogle Scholar. Experiments with microspheres has showed that most of particle of this size would be clear out by the lung17. If your cancer spreads to your abdomen or peritoneal space, IP chemotherapy can help target the cancer cells there. Intraperitoneal injection or IP injection is the injection of a substance into the peritoneum (body cavity). At 24h after injection, the intensity of free dye was 100 folds less than the DiR labeled cells (from the bar value. In mouse, the intraperitoneal and subcutaneous LD 50 values are 138 and 650 mg kg 1, respectively. In humans respiratory side-effects were reported in five subjects taking mefloquine, but these cases constituted only 0.1% of studied population (Lobel et al., 2001). During the observation, the body weight changes and fecal blood and their survival date was faithfully record. Acute colitis was induced in C57BL/6 male mice by feeding 5% DSS (molecular weight 40000Da; Sigma) dissolved water for 5 days, followed by five days of regular drinking water according to our previously published study63. Obermeier, F. et al. n=3 per group. The accessibility of the therapeutic cells to their expectable target site is strongly dependent on the route of administration used. Intraperitoneal Drug Administration - ScienceDirect Proper Method for Intraperitoneal Injections Would you like email updates of new search results? It is estimated that as many as 1.4million Americans and 2.4million Europeans are suffering from these diseases1,2. doi: 10.1002/14651858.CD005284.pub3. ADS Samples were prepared and tested as previously reported47. Here, we also compare the expression of FoxP3, which is frequently used to quantitate Treg cells. (D) Semi-quantitative fecal occult blood test on day 3. These findings could be advanced by studying how the route of injection affects the organs in the peritoneal cavity. We also evaluated serum TSG-6 in three MSCs administration route. For intraperitoneal administration, restrain the mouse with one hand and tilt the head backward to expose the abdomen. Department of Digestive Diseases, State Key Laboratory of Cancer Biology, Xijing Hospital, Fourth Military Medical University, Xian, 710032, China, Min Wang,Cong Liang,Hao Hu,Lin Zhou,Bing Xu,Xin Wang,Ying Han,Yongzhan Nie,Jie Liang&Kaichun Wu, Department of Gastroenterology, Xian Childrens Hospital, 710006, China, Department of Respiratory and Gastroenterology, Second Peoples Hospital, Xian, 710005, China, Department of Gastroenterology, PLA No.5 Hospital, Yinchuan, 750004, China, You can also search for this author in 2020 May 9;12(5):439. doi: 10.3390/pharmaceutics12050439. Kurtz, A. Mesenchymal stem cell delivery routes and fate. Gastroenterology 140, 17851794, doi: 10.1053/j.gastro.2011.01.055 (2011). An improved mouse model of sepsis based on intraperitoneal injections of the enriched culture of cecum slurry . Incidence and phenotype of inflammatory bowel disease based on results from the Asia-pacific Crohns and colitis epidemiology study. They found that PCs can directly migrated from peritoneal cavity and some of them were found at intestinal villi. This study was supported by combined grants from the National Natural Science Foundation of China (No. In a previous study, 14 mice were exposed to SWCNTs through intravenous (IV) injection to determine whether there were any adverse effects caused by SWCNTs on the mouse brain and also to find a safe application dosage if possible. Samples were centrifuged at 30,000g for 20minutes and stored at 80C until cytokine determination. Other than preformed at the site of injury, MSCs has showed ability to exert their therapeutic effects distally. Liotta, F. et al. Furthermore, the corresponding mesentery lymph nodes (MLNs) also showed relatively high MSCs existence (Fig. Certainly, cells are not microsphere which is structural rigid, they are well acknowledged about their deformation, however, a plenty of experimental data support that a substantial amount of MSCs are entrapped in the lung when following IV route16. Vilquin, J. T. & Rosset, P. Mesenchymal stem cells in bone and cartilage repair: current status. [11] The effects of this study were the onset of flu-like symptoms, emesis, and abdominal pain. Stem cells international 2013, 732742, doi: 10.1155/2013/732742 (2013). Intraperitoneal injections are the preferred method of administration in many experimental studies due to the quick onset of effects post injection. Admittedly, there may be an overlook of MSCs existence due to the tissue selection of frozen section and sensitivity of fluorescence imaging, the therapeutic differentiation of MSCs in our study were not clearly observed. 2014ZX09508002). This concern arises because MSCs has an estimated diameter of 2030m15,16. Gut 63, 588597, doi: 10.1136/gutjnl-2013-304636 (2014). 81421003 and No. Comparison of colonic proliferation 7 days after MSCs injection. [citation needed]. [20] There needs to be more research done to determine appropriate dosing and combinations of these drugs to advance intraperitoneal drug delivery. [12] This study demonstrates how intraperitoneal injections can be used to help diagnose diseases by providing direct access to the peritoneal cavity and affecting the organs in the cavity. Zhang, B. et al. (B) Quantification of % Ki-67+ cells/crypt, the IP and IA>IV>DSS control, n=6 mice/group; n=3 for the control group. PubMed Central The immunohistochemistry indicated higher repair proliferation (Ki-67) and more FoxP3+ cells accumulation of IP group. But this study at least pointed out the possible migration route for cells by intraperitoneal injection. The transplanted lymphocytes can produce immunoglobulin (Ig), respond to antigens, and survive for months in this chimeric model (hu-PBL SCID). Article A simple dengue vaccine evaluation system was established using a model of dengue type 2 virus (DENV2) infection in immunocompetent mice. PDF Intraperitoneal (IP) Injection in Rats and Mice SOP The IP 'option' was not adopted, however, because the standard treatment had shifted to IV cisplatin plus . Stem Cells 29, 15721579, doi: 10.1002/stem.708 (2011). After intraperitoneal injections, 30% of the female mice died, compared with 3% of the male. Though genetic and environmental factors are believed to be involved in the disease, not much progress has been made on therapy. Gynecol Oncol 81, 7781, doi: 10.1006/gyno.2000.6108 (2001). Blood 109, 46274634, doi: 10.1182/blood-2006-12-064345 (2007). Some of the examples depict situations where IP injections are not ideal, while others prove the advantageous uses if this delivery method. In our study, we tracked the GFP+ MSCs colon colonization, but our results also showed the short stay of MSCs after injection. These non-target entrapments made IV route less cells immigration and colonization and may be a hindrance for MSCs to fully display its therapeutic effects. Provided by the Springer Nature SharedIt content-sharing initiative. MeSH A consensus report written on behalf of the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT). & Yong, K. Factors that influence short-term homing of human bone marrow-derived mesenchymal stem cells in a xenogeneic animal model. DiR labeling showed no harm to the MSCs viability13 (Supplementary Figure S3). The IP technique is an easy technique to master. Vishnubalaji, R., Al-Nbaheen, M., Kadalmani, B., Aldahmash, A. Inflammatory bowel disease (IBD). In addition, the effects of different dosing modalities (e.g., oral administration and intraperitoneal injection) on the . (CS), Intraperitoneal, Polymicrobial, and Antibiotics available under aCC-BY 4.0 International license. Colitis showed varying degrees of alleviation after three ways of MSCs transplantation and the IP injection showed the highest survival rate of 87.5% and displayed the less weight loss and quick weight gain. We selected the day 3 as observation time point. Journal of biomedical science 15, 585594, doi: 10.1007/s11373-008-9256-9 (2008). For some chemotherapy, such as ovarian cancer, IP injection is used to attempt to localize the drug . & Ramesh, T. Comparative investigation of the differentiation capability of bone-marrow- and adipose-derived mesenchymal stem cells by qualitative and quantitative analysis. Thus there is a strong impetus to seek more effective approaches for disease management. Fluorescent intensity was quantified and processed using the Living Image Software (Version 4.2; Caliper Life Science). Mice were maintained in a light/temperature-controlled room and allowed to freely access to chow diet and water. Lateralized activation of the insular cortex is also observed in adult . Google Scholar. 81370585, No. In addition, from the point of cell morphological appearance, most of MSCs kept intact in IP group, while in AI route, other than active MSCs, cell fragments and debris were also identified in the lumen (Fig. Internet Explorer). In addition, IP showed more intense Ki-67 stain in bottom of the crypt, which suggested more active mucosa repair proliferation (Fig. injections. The physiologic characteristic of the peritoneal cavity not only helps remove toxic metabolites from the body, but also provides a useful portal of entry in the body for several pharmacological agents. Although the decline in AGT activity in the liver was reversible, the activity remained at 75% of basal levels for up to 25 h after the final injection. & Gratwohl, A. They are mitomycin C, cisplatin, carboplatin, oxaliplatin, irinotecan, 5-fluorouracil, gemcitabine, paclitaxel, docetaxel, doxorubicin, premetrexed, and melphalan. Intraperitoneal (IP) Injection (Injection of Sodium Pentobarbital . Models should begin with local tissue infection, so that bacterial . Intra-abdominal adhesions can be a considerable source of morbidity and mortality. GAPDH mRNA was used as an internal control to normalize mRNA expression. Targeting improves MSC treatment of inflammatory bowel disease. All experimental procedures performed were approved by Animal Welfare and Ethics Committee of the Fourth Military Medical University (FMMU), which are in accordance with the NIH guidelines. NIR fluorescent dye, 1, 1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR; DiIC18(7), Molecular Probes, Invitrogen, Carlsbad, CA) was used for labeling the cells as previously reported65. ObjectivesThis study aimed to investigate the efficacy and safety of intratympanic or postauricular subperiosteal glucocorticoid injection combined with systemic glucocorticoid in the treatment of sudden sensorineural hearing loss (SSNHL).MethodsThis study is a prospective randomized controlled study. There are few examples of the use of intraperitoneal injections in humans cited in literature because it is mainly used to study the effects of drugs in mice. After wishing with PBS, the sections were incubated 1h at room temperature with secondary antibody, then visualized by diaminobenzidine (DAB). Stem cells and development 21, 21892203, doi: 10.1089/scd.2011.0674 (2012). Kushnir, C. L., Fleury, A. C., Silver, D. F. & Spirtos, N. M. Intraperitoneal Catheter Placement: The Hammock Technique. The number of therapeutic cells that can migrate and colonize at the injury site is a decisive prerequisite for the success of cytotherapy. DSS only served as control. & Prockop, D. J. Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF-kappaB signaling in resident macrophages. 6B). In most experimental studies, the MSCs treatment usually require at least 1106 cells/mouse, more frequently, a dose as high as 5106 cells/mouse to observe any effect12. Comparison of molecular profiles of human mesenchymal stem cells derived from bone marrow, umbilical cord blood, placenta and adipose tissue. PubMed Central Treatment of dextran sodium sulfate-induced experimental colitis by adoptive transfer of peritoneal cells. This finding was consistent with previous published paper23, in which the intraperitoneal MSCs migrating and engraft at inflamed colon were identified by Tc-99m SPECT imaging in TNBS induced colitis. Clinical and experimental immunology 116, 238245 (1999). MSCs induced more Ki-67 positive cells in the lower part of the crypt than the DSS control. The serum concentration of TNFinduced protein 6 (TSG-6) was measured in DSS colitic mice at 48 and 72hours after different routes of MSCs administrations. Google Scholar. Stem cells (Dayton, Ohio) 24, 386398, doi: 10.1634/stemcells.2005-0008 (2006). Sci Rep 6, 30696 (2016). Adhesions are a leading cause of secondary infertility in women, accounting for 15% to 20% of cases. Fresh feces from animals were collected for occult blood test, using fecal occult blood kit (Baso Diagnostics Inc., Zhuhai, China) according to the manufactures recommendations. Then sections were washed and blocked with normal nonimmunone goat serum for 30min. Ex-vivo study was carried out at 1 day post-injection. The fluorescence imaging disclosed higher intensity of engrafted cells in inflamed colon and the corresponding mesentery lymph nodes (MLNs) in IP and AI groups than the IV group. The formation of the aggregates probably limits access of the cells to the systemic circulation. Histopathological alterations in the mouse brain were detected after SWCNTs exposure. 8600 Rockville Pike Pentobarbital sodium Injection Caution. Bioengineered. Stem cell reviews 10, 127144, doi: 10.1007/s12015-013-9468-x (2014). Collagen Deposition was assessed with phosphomolibidic acid-picrosirius red staining. Before Their findings showed that intraperitoneally injected MSCs would form aggregates with macrophages and lymphocytes in peritoneal cavity and remotely secreted TSG-6. PDF EUTHANASIA REFERENCE MANUAL - HumanePro CAS Infiltration (I): 0, no infiltrate; 1, infiltrate around crypt basis; 2, infiltrate reaching to lamina muscularis mucosa layer; 3, extensive infiltration reaching the muscularis mucosa with abundant edema; 4, infiltration of the submucosa layer. However, if proper placement of the needle occurs, this is not necessary. Side effects. Mol Ther 18, 13651372, doi: 10.1038/mt.2010.54 (2010). Pharm Res. Currently, there are a handful of drugs that are delivered through intraperitoneal injection for chemotherapy. Upon intravenous and intraperitoneal injection of stressed MSA, fluorescent "hotspots" were observed in the spleens, livers and lungs. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Mice were under intensive observation for 12 days. The following approaches are novel, and require further testing in humans before being accepted as potential treatment options: Federal law restricts this drug to use by or on the order of a licensed veterinarian. Buy cheap Viagra Plus online no RX - Effective online Viagra Plus However, whether the lymphocytes actually . Intraperitoneally applied drug forms are supposed to be located in the peritoneal cavity. Sonazoid was utilized to aid with contrast-enhanced ultrasonography by enhancing the peritoneal and pleural cavities. The IP and AI groups showed mean 50.4% and 46.7% Ki-67+ cells/crypt respectively. Mice were made diabetic by intraperitoneal injection of streptozotocin, which led to a 2- to 2.5-fold increase in plasma glucose. Cardiovascular research 96, 208209; discussion 210203, doi: 10.1093/cvr/cvs202 (2012). The most efficient method to inject small animals is a two-person method where one holds the rodent and the other person injects the rodent at about 10 to 20 degrees in mice and 20 to 45 degrees in rats. Lee, R. H. et al. The coefficient 13.5 was empirically determined such that 1U MPO activity represents the amount of enzyme that will reduce 1 mol peroxide/min. Intraperitoneal injection of magnetic Fe3O4-nanoparticle induces On the contrary, the most significant advantage of IP and AI routes is that cells do not immediately enter to the blood flow, allowing sufficient blood dilution. & Dittel, B. N. Isolation of mouse peritoneal cavity cells. Intraperitoneal injections are a way to administer therapeutics and drugs through a peritoneal route (body cavity). 4 The scalp was disinfected and a midline incision was made in the skin. Nature medicine 5, 309313, doi: 10.1038/6529 (1999). 2, Haidian District, Beijing 100193, China. In order to compare the difference of MSCs colonization among the three delivery routes, a nontoxic NIR tracer DiR was introduced to label MSCs. Inflammatory Scores were calculated using a score system66: Epithelium (E): 0, normal morphology; 1, loss of goblet cells; 2, loss of goblet cells in large areas; 3, loss of crypts; 4, loss of crypts in large areas. Hommes, D., Colombel, J. F., Emery, P., Greco, M. & Sandborn, W. J. Opioids can produce peripheral analgesic effects by activation of opioid receptors on sensory nerves. Federal government websites often end in .gov or .mil. This study goes over the dosages, adverse effects, and more of using intraperitoneal injections of anesthesia.[18]. Just mentioned above, immune cells and MSCs interaction in aggregates promotes TSG-6 secretion and contributed to the colitis recovery. Histopathological comparison of colitis after 3 days MSCs delivery. 2018 Jul;6(3):207-216. doi: 10.29252/beat-060304. [13] The patient was a 51-year-old male who was hospitalized. Therapeutic effects of a single injection of human umbilical mesenchymal stem cells on acute and chronic colitis in mice, Mechanism and therapeutic effect of umbilical cord mesenchymal stem cells in inflammatory bowel disease, Human induced pluripotent stem cell-derived mesenchymal stem cells promote healing via TNF--stimulated gene-6 in inflammatory bowel disease models, Conditioned medium of mesenchymal stem cells pretreated with H2O2 promotes intestinal mucosal repair in acute experimental colitis, Mesenchymal stromal cells-derived matrix Gla protein contribute to the alleviation of experimental colitis, Supporting the gastrointestinal microenvironment during high-dose chemotherapy and stem cell transplantation by inhibiting IL-1 signaling with anakinra, The recruitment of extra-intestinal cells to the injured mucosa promotes healing in radiation enteritis and chemical colitis in a mouse parabiosis model, Prolyl hydroxylase 2 silencing enhances the paracrine effects of mesenchymal stem cells on necrotizing enterocolitis in an NF-B-dependent mechanism, Challenges and opportunities targeting mechanisms of epithelial injury and recovery in acute intestinal graft-versus-host disease, http://ctep.cancer.gov/highlights/20060105_ovarian.htm, http://creativecommons.org/licenses/by/4.0/, CCR2-overexpressing mesenchymal stem cells targeting damaged liver enhance recovery of acute liver failure, Assessment of endothelial colony forming cells delivery routes in a murine model of critical limb threatening ischemia using an optimized cell tracking approach, Mesenchymal Stem Cells Promote Intestinal Mucosal Repair by Positively Regulating the Nrf2/Keap1/ARE Signaling Pathway in Acute Experimental Colitis, Cross Talk between Mesenchymal Stem/Stromal Cells and Innate Immunocytes Concerning Lupus Disease. Google Scholar. ADS Very few reports pay attention to factors applied in the clinic, such as injection or exposure routes, which has highly impact on stem cell therapeutic efficiency for IBD12. Clinical use of bone marrow, bone marrow concentrate and expanded bone marrow mesenchymal stem cells in cartilage disease. Every 1107 cells were incubated with 10mL DiR solution (PBS based containing 3.5g/mL dye and 0.5% ethanol) for 30min at 37C. Am J Gastroenterol 105, 289297, doi: 10.1038/ajg.2009.579 (2010). drug availability and human abuse potential; 10. compatibility with species, age, and health status; 11. Nature biotechnology, doi: 10.1038/nbt.2816 (2014). MSCs organ distribution and engraftment was analyzed and quantified by GFP+ MSCs as well as Near-infrared fluorescence imaging. IP, intraperitoneal injection; IV, intravenous injection; AI anal injection; n=68 for treatment group, n=3 for DSS control. How to cite this article: Wang, M. et al. In their study, PKH26 (a yellow-orange fluorescent dye) labeled PCs were injected intraperitoneally into healthy rat. To determined cytokine in colon mucosa, protein extracts were isolated by homogenization of colonic segments (50mg tissue/mL) in 50mmol/L Tris-HCl, pH 7.4, with 0.5mmol/L dithiothreitol and 10 g/mL of a cocktail of proteinase inhibitors (Sigma). Intraperitoneal but not intravenous cryopreserved mesenchymal stromal cells home to the inflamed colon and ameliorate experimental colitis. . MSCs has been well characterized of producing a range of modulatory cytokine, which inspires the designation of these cells as injury drugstore44. Additionally, the clinical translation is another concern. The Journal of infectious diseases 198, 456464, doi: 10.1086/590112 (2008). PubMed The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. PDF Proper Method for Intraperitoneal Injections - PerkinElmer Yui, S. et al. (A) Representative IHC images of each MSCs treatment group. But for the IP injection, because of more cell accumulation in the inflamed colon, less initial cells might reach minimum effective cell dose. Gastroenterology 145, 158165 e152, doi: 10.1053/j.gastro.2013.04.007 (2013). Khalil, P. N. et al. Please enable it to take advantage of the complete set of features! Arthritis and rheumatism 56, 11751186, doi: 10.1002/art.22511 (2007). In various preclinical models, saroglitazar has been shown to prevent & reverse symptoms of NASH. Berberich, S., Forster, R. & Pabst, O. Regenerative medicine 1, 589604, doi: 10.2217/17460751.1.4.589 (2006). At 72h, the IP groups showed significant higher level of TSG-6 than AI groups and DSS control (P=0.023 and P=0.005, respectively). In addition, fewer female mice achieved surgical anesthesia, suggesting a narrow therapeutic window for intraperitoneal KX in female mice. . Gut epithelium is intact and lacks cytokines or chemokines attraction; 2) most of PCs are immune cells, such as B cells (5060%), macrophages and mast cells (30%) and T cells (510%)28. Estes, J. et al. Sci Rep 5, 16760, doi: 10.1038/srep16760 (2015). 2B). The results of this IP injection were the disappearance of the ascites associated with the rupture. Intraperitoneal injections may also allow too-rapid entry of bacteria or LPS into the blood. In general, it is preferred when large amounts of blood replacement fluids are needed or when low blood pressure or other problems prevent the use of a suitable blood vessel for intravenous injection. IP showed better colitis recovery and might be the optimum MSCs delivery route for the treatment of DSS-induced colitis. Horwitz, E. M. et al. Intraperitoneal injection or IP injection is the injection of a substance into the peritoneum (body cavity). Statistical significance was determined using one-way ANOVAs or Students t tests. You are using a browser version with limited support for CSS. Because of the injection of cannabis, the patient was predicted to have some level of THC in the blood from absorption. was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity . Available at: http://ctep.cancer.gov/highlights/20060105_ovarian.htm (Accessed: 7th April 2016) (2006). Intraperitoneal Chemotherapy - Memorial Sloan Kettering Cancer Center Further control study comparing bowel signals on healthy mice and DSS mice after MSCs injection showed weaker NIR signal on healthy bowel in all three routes, which indicated fewer MSCs migration to the colon without colitis (Supplementary Figure S5). (B) Quantification of FoxP3+ cells, the IP>IA and IV>DSS control, n=6 mice/group; n=3 for the control group. Metabolite tracing, radioactive uptake experiments, and CRISPR screens demonstrate that FLVCR1 is the major plasma-membrane choline transporter. [19] It was concluded that IP administration should not be used over intravenous therapy due to high radiation absorption in the intestines. We have proposed that safe and effective protection against the development of adult onset cancers may be achieved by vaccination against tissue-specific self-proteins that are "retired" from expression at immunogenic levels in normal tissues as we age, but are overexpressed in emerging tumors. Cell stem cell 5, 5463, doi: 10.1016/j.stem.2009.05.003 (2009). Abstract Intraperitoneal (IP) injection is frequently reported to be as effective as intravenous (IV) injection. Injected dissociative agent combinations. An official website of the United States government. Study on pharmacokinetics-Study on pharmacokinetics-Innostar Nonmyeloablative stem cell therapy enhances microcirculation and tissue regeneration in murine inflammatory bowel disease. Garcia-Bosch, O., Ricart, E. & Panes, J. [1] Fluids are injected intraperitoneally in infants, also used for peritoneal dialysis.
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