Pentobarbital sodium Injection for Animal Use - Drugs.com . Chemotactic cytokines might be involved and responsible for MSCs attraction. M.W., C.L. Just mentioned above, immune cells and MSCs interaction in aggregates promotes TSG-6 secretion and contributed to the colitis recovery. We selected the day 3 as observation time point. Intraperitoneal injection (IP), Intravenous injection (IV) or anal CAS Stem cell transplantation: the lung barrier. Samples were prepared and tested as previously reported47. MPO activity per gram of wet tissue was calculated as: MPO activity (U/g wet tissue)=(A450) (13.5)/tissue weight (g). The levels of immunomodulatory cytokines were compared by real time-PCR and ELISA. Article (CS), Intraperitoneal, Polymicrobial, and Antibiotics available under aCC-BY 4.0 International license. Methods of euthanasia likely to elicit distress vocalizations or pheromones that other animals could hear or smell should be performed in another location, if transportation distress can be minimized. How to cite this article: Wang, M. et al. The complications associated with IP injection are major concern. Many published studies have showed the benefits of IV delivery in IBD treatment. Google Scholar. For the other inflammatory cytokines, such as IL-6, IL-1 and IFN-, the expression levels varied among the groups and IP delivery did not show evident advantages over others (Supplementary Figure S7). 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. More recently the IP route has been used for chemotherapy in patients with intra-abdominal malignancies, i.e. Mice were sacrificed and colons were collected for histological analysis. Journal of biomedical science 15, 585594, doi: 10.1007/s11373-008-9256-9 (2008). Multiple Intravenous Transplantations of Mesenchymal Stem Cells Intraperitoneal Injection - an overview | ScienceDirect Topics Magnetically assisted intraperitoneal drug delivery for cancer chemotherapy. Peri/postnatal development in rats was impaired with reduced pup weights, increased stillbirths, and increased pup mortality concurrent with maternal toxicity after intraperitoneal administration of tazobactam alone at doses 320 mg/kg/day (2 times the human dose based on body surface area) or of the combination piperacillin and tazobactam at . Mouse insulin gradually decreased and was no more detectable 13 weeks after STZ injection. A . Tyndall, A. 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). Cells, tissues, organs 169, 1220 (2001). Comparison of colonic inflammatory cytokine TNF- and IL-10 at day 3. A., Ong, J. F. & Karp, J. M. Mesenchymal stem cells: immune evasive, not immune privileged. Six leukemia patients with Crohns disease treated with allogeneic marrow transplantation and four of five patients remained CD free 6 to 15 years after transplantation10. 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. Several medications such as antibiotics are given via the intraperitoneal (IP) route in PD patients to treat episodes of peritonitis. Clinical Ovarian and Other Gynecologic Cancer 5, 2426, doi: 10.1016/j.cloc.2011.08.001 (2012). MathSciNet Intraperitoneal - an overview | ScienceDirect Topics 2A), which guarantee the less interference from the background signal that coming from free dye. Lee, R. H. et al. PubMed supply of IGF-I to adolescent and adult animals or humans is not known. Collagen deposition is another indicator for wound healing, however, extensive collagen deposition may hamper the gut reconstitution14. Antunes, M. A. et al. Intraperitoneal chemotherapy for peritoneal metastases: an expert opinion. Google Scholar. Insular cortex is a critical brain region that participates in the interoceptive sensations. MSCs organ distribution and engraftment was analyzed and quantified by GFP+ MSCs as well as Near-infrared fluorescence imaging. Vilquin, J. T. & Rosset, P. Mesenchymal stem cells in bone and cartilage repair: current status. In the meanwhile, the colonic homogenates were collected and colonic IL-10, TNF- were measured by ELISA assays. Complications associated with intraperitoneal chemotherapy catheters. The immunohistochemistry indicated higher repair proliferation (Ki-67) and more FoxP3+ cells accumulation of IP group. Murine Responses to Endotoxin: Another Dirty Little Secret? For example, discharged accompany with stool or cleared out by lung microphage. Br J Rheumatol 36, 390392 (1997). Journal of Crohns & colitis 6 Suppl 2, S224S234, doi: 10.1016/s1873-9946(12)60502-9 (2012). Brown, S. L. et al. Highlighting the importance of choline metabolism . The delivery of OK-432 occurred a total of four times in a span of one week. Drug delivery systems for intraperitoneal therapy. They are one of the few ways drugs can be administered through injection, and have uses in research involving animals, drug administration to treat ovarian cancers, and much more. The fecal occult blood test on the day 3 also showed nearly complete absence of occult blood in IP group (Figure 1D). In patients with peritoneal surface malignancies, perioperative IP chemotherapy has been used with good results. Skin application of non-rodents (miniature pigs) Intraperitoneal administration allows quick reabsorption of large volumes of substances and is the preferred injection route for nonirritant, isotonic solutions [7,11]. 2, Haidian District, Beijing 100193, China. It also shows how easily substances are absorbed through the peritoneal cavity after an IP injection. HHS Vulnerability Disclosure, Help The site is secure. By using this techniques, the catheter complications, in particular obstruction, bowel and vaginal cuff perforation were greatly reduced61. Intraperitoneal injection or IP injection is the injection of a substance into the peritoneum (body cavity). (A) Representative IHC images of each treatment group. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/, Wang, M., Liang, C., Hu, H. et al. Shariati M, Zhang H, Van de Sande L, Descamps B, Vanhove C, Willaert W, Ceelen W, De Smedt SC, Remaut K. Pharm Res. Their findings showed that intraperitoneally injected MSCs would form aggregates with macrophages and lymphocytes in peritoneal cavity and remotely secreted TSG-6. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Article Language links are at the top of the page across from the title. Provided by the Springer Nature SharedIt content-sharing initiative. [2] Killing the rodent through an intraperitoneal route was originally recommended over other routes such as inhalants because it was thought to be more efficient and ethical. These findings may benefit clinic practice. Once the animal is properly restrained (as described above for SC injections) the injection site is . study on peritoneal cells (PCs) migration to gut may give us some hints27. However, one recent published paper showed inconsistent results with ours, in which IV injection was identified better in comparison with intraperitoneal injection31. IBD can be painful and persistent for life, which might decrease the quality of life. In addition, MSCs showed inhibitory effects on proliferation of memory T-cells by direct cell contact52. gynecological and gastrointestinal cancers and has shown very promising results. As expected, similar scenario was observed in our study: Compared with IP and AI, IV route indeed caused more cell entrapment in the lung, moreover, mononuclear phagocytic system, the liver and spleen also showed a great amount of MSCs present. CAS Frontiers | Efficacy of intratympanic or postauricular subperiosteal Intraperitoneal foreign bodies such as suture material, clips, and mesh also contribute to adhesion formation. Intraperitoneal (IP) route of drug administration in laboratory animals is a common practice in many in vivo studies of disease models. Scientific Reports (Sci Rep) Maximum 15 10 slow injection 10 2 (divided in 2-3 sites) 0.5 (Max 2 ml limit) Minipig Ideal 10 1-5 bolus 1 1 0.25 Maximum 15 10 slow injection 20 3 (divided in 2-3 sites) 0.5 (Max 5 ml limit per site) * Bolus injections are typically dosed in less than 1 minute. Journal of biomedical optics 11, 050507, doi: 10.1117/1.2364903 (2006). Horwitz, E. M. et al. 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). CAS 1A) showed the time point of DSS given and MSCs therapy. In COX-2 blocking control experiments, mice received FA-NPs (0.5 mg/kg) 1 h after an intraperitoneal injection of celecoxib (10 mg/kg) to block binding of FA to the COX-2 active site. Indeed, Mariana et al. Mice were under intensive observation for 12 days. Cell stem cell 4, 206216, doi: 10.1016/j.stem.2009.02.001 (2009). CAS There was a dose-dependent decrease in AGT activity in liver tissues of CD-1 mice to 24% of basal levels after four hourly intraperitoneal injections of O 6-methylguanine (110 mg/kg). injection, or EBI) remains the most humane method available. Most importantly, IP was found to have highest serum TSG-6 at both 48h and 72h and showed statistical significance when comparing with AI and DSS control at 72h. These findings, to some extent, may help to understand why IP is better than AI and IV. 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. (A,B) Representative colon images and quantification of colon length; (C) myeloperoxidase (MPO) activity in colonic protein extracts; (D,E) Representative H&E staining and corresponding severity score; (F,G) Representative sirius red staining and quantification of collagen deposition. If there is negative pressure, proceed with the injection depress the plunger until the solution has been fully administered. This study compared intraperitoneal injections, intravenous injections, and anal injections. The formation of the aggregates probably limits access of the cells to the systemic circulation. Targeting improves MSC treatment of inflammatory bowel disease. [6] In 1968, melatonin was delivered to rats intraperitoneally in order to study how brain serotonin would be affected in the midbrain. Secondly, as mentioned above, there are plenty of immune cells in peritoneal cavity28, which are indispensable component of MSCs aggregates. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Intraperitoneal (IP) Injection (Injection of Sodium Pentobarbital . Intraperitoneal injection of lithium chloride induces lateralized This site needs JavaScript to work properly. In addition, IP showed more intense Ki-67 stain in bottom of the crypt, which suggested more active mucosa repair proliferation (Fig. Another study by coating MSCs with VCAM-1 also exhibited an increased MSCs migration to the inflamed colon and promoted tissue repair capacity25. Injections, also known as shots, deliver liquid medications, fluids, or nutrients directly into a person's body. But this study at least pointed out the possible migration route for cells by intraperitoneal injection. Slider with three articles shown per slide. Hommes, D., Colombel, J. F., Emery, P., Greco, M. & Sandborn, W. J. Arthritis and rheumatism 56, 11751186, doi: 10.1002/art.22511 (2007). Haematologica 93, 14571465, doi: 10.3324/haematol.12553 (2008). Stem cells (Dayton, Ohio) 30, 15751578, doi: 10.1002/stem.1118 (2012). Review article: stem cell therapies for inflammatory bowel disease - efficacy and safety. Injected dissociative agent combinations. In IV group, most of MSCs were trapped in the lung, liver and spleen, while the cell that immigrated to the colon was not too much. Cell stem cell 9, 1115, doi: 10.1016/j.stem.2011.06.008 (2011). This study was designed (1) to examine a novel route of opioid administration, the intraperitoneal injection; (2) to compare this to interpleural application, and (3) to compare opioid with local anesthetic effects under both conditions.Methods. 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. Fluorescent intensity was quantified and processed using the Living Image Software (Version 4.2; Caliper Life Science). Thus, the aim of the current study was to find out the potential safety range of medical use. 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. Female nude mice (Envigo) were anesthetized by intraperitoneal (IP) injection of ketamine/xylazine and immobilized in a stereotactic frame (Stoelting). Article In this study, intraperitoneal (IP) injection was used to mimic the human administration route. Comparison of colonic proliferation 7 days after MSCs injection. They are mitomycin C, cisplatin, carboplatin, oxaliplatin, irinotecan, 5-fluorouracil, gemcitabine, paclitaxel, docetaxel, doxorubicin, premetrexed, and melphalan. Although widely used as a means of administering substances, particularly injectable anaesthetics, this is an inherently unreliable technique, since inadvertent injection of some material into the gut, abdominal fat and subcutaneous tissues is a relatively frequent . Every 1107 cells were incubated with 10mL DiR solution (PBS based containing 3.5g/mL dye and 0.5% ethanol) for 30min at 37C. Here, we also compare the expression of FoxP3, which is frequently used to quantitate Treg cells. Like pharmacological treatment, the cell dosing might also be an important issue for MSCs therapeutic success21. Epub 2020 Mar 18. 3) and the IV group preserved fewer cell number. Internet Explorer). 81421003 and No. of the needle exposed to assure 4-5mm injection depth. However, whether the lymphocytes actually . ADS Macrophage Reverse Cholesterol Transport | Circulation Human mesenchymal stem cells license adult CD34+ hemopoietic progenitor cells to differentiate into regulatory dendritic cells through activation of the Notch pathway. Figure 1. Google Scholar. At day 5, mice were randomized and injected with MSCs (1106, 200L in volume) by three delivery routes (IP, AI and IV). Intramuscular. Gastroenterology 140, 17851794, doi: 10.1053/j.gastro.2011.01.055 (2011). Background Saroglitazar is a novel PPAR-/ agonist with predominant PPAR- activity. One article reviews the injection of sodium pentobarbital to euthanize rodents intraperitoneally. In various preclinical models, saroglitazar has been shown to prevent & reverse symptoms of NASH. Stem cell reviews 10, 127144, doi: 10.1007/s12015-013-9468-x (2014). Stem Cell Res Ther 3, 51, doi: 10.1186/scrt142 (2012). Stem cells (Dayton, Ohio) 24, 386398, doi: 10.1634/stemcells.2005-0008 (2006). In this study, we compared therapeutic efficacy of three MSCs administration routes in DSS-induced colitis. Overall, this section provides a few examples of the effects and uses of intraperitoneal injections in human patients. Google Scholar. Ko, I. K. et al. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in It was concluded that there is evidence that IP may not be the best method of euthenasia due to possibilities of missinjection. Stem cell research & therapy 6, 55, doi: 10.1186/s13287-015-0066-5 (2015). & Ramesh, T. Comparative investigation of the differentiation capability of bone-marrow- and adipose-derived mesenchymal stem cells by qualitative and quantitative analysis. Quantitative data are presented as the meanSD. All reactions were performed in triplicated. PubMedGoogle Scholar. some potent chemo and radio-labeled drugs)59. Survival curve plots and Kaplan-Meier analyses were performed using Prism 5.0 software. 7 . PDF An improved mouse model of sepsis based on intraperitoneal injections Article Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Experiments with microspheres has showed that most of particle of this size would be clear out by the lung17. Schrepfer, S. et al. Further study demonstrated TSG-6 alone was sufficient to reduce intestinal inflammation in mice with colitis. Insert the needle at a shallow angle through the . Intraperitoneal injections are a way to administer therapeutics and drugs through a peritoneal route (body cavity). 2014 Apr 26;(4):CD005284. Condition. When searching "intraperitoneal injections" a majority of the results relate to the use of IP injections in murine or rat models in order to study the effect of some drug or chemical. Gonzalez, M. A., Gonzalez-Rey, E., Rico, L., Buscher, D. & Delgado, M. Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. The primer sequences used were listed in Supplementary Table S1. Gastroenterology 145, 158165 e152, doi: 10.1053/j.gastro.2013.04.007 (2013). Federal law restricts this drug to use by or on the order of a licensed veterinarian. Intraperitoneal injections are the preferred method of administration in many experimental studies due to the quick onset of effects post injection. 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. 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. Our findings showed that the GFP+ MSCs were migrated to the inflamed colon, even passed through the whole intestinal wall and reached the luminal side. (D) Semi-quantitative fecal occult blood test on day 3. Your peritoneal space. official website and that any information you provide is encrypted (A) Scheme of the treatment, the day of MSCs injection was defined as day 0. PubMed Gastroenterology 132, 944954, doi: 10.1053/j.gastro.2006.12.029 (2007). Blood 118, 330338, doi: 10.1182/blood-2010-12-327353 (2011). It is more often applied to animals than to humans. With the computer-assisted software, we calculated the density of collagen fibers (%) of all groups. The holder retains the arms of the animal and tilts the head lower than the abdomen to create optimal space in the peritoneal cavity. Here, three different MSCs delivery routes: intraperitoneal (IP), intravenous (IV) and anal injection (AI) were compared on DSS-induced colitic mice model. Cells (human GBM-derived stem cells, GBM-8) 46 were cultured in Neurobasal medium supplemented with heparin, B27, . Blonski, W., Buchner, A. M. & Lichtenstein, G. R. Treatment of ulcerative colitis. An example of when intraperitoneal injections are not ideal is given in a study where the best route of administration was determined for cancer biotherapy. Sminia, T., Soesatyo, M., Ghufron, M. & Thepen, T. The migration of peritoneal cells towards the gut. Samples were frozen and thawed 3 times, centrifuged at 30,000g for 20minutes. We next compared serum TSG-6 level in three administration routes at 48h and 72h respectively after MSCs transplantation using ELISA (Fig. A consensus report written on behalf of the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT). eCollection 2021. PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment. Comparison of colonic FoxP3 expression 7 days after MSCs 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. A study was conducted to determine the best route of administration to transplant mesenchymal stem cells for colitis. While the DiR labeled cells showed very different cell distribution. & Correa, D. The MSC: an injury drugstore. 4A,B). Importantly, we identified different migration fates of MSCs and traced their ultimate location of three administration ways for the first time. Currently, two types of stem are used for the treatment of IBD, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). [13] The patient was a 51-year-old male who was hospitalized. Streptozotocin-induced Diabetic Models In Mice And Rats & Dittel, B. N. Isolation of mouse peritoneal cavity cells. Since the IP injection induced more cells migration to the inflamed colon, we further compared the difference in mucosa healing of different delivery routes. The GFP+ MSCs were found at inflamed colon in both IP and AI groups 24h after MSCs injection. Adv Exp Med Biol 371A, 6165 (1995). injections. Evid Based Complement Alternat Med. [17] Contrast agents were administered intraperitoneally instead of intravenously to avoid errors and challenges. [citation needed], In humans, the method is widely used to administer chemotherapy drugs to treat some cancers, particularly ovarian cancer. From two streams of research, experimental and clinical, stem cell therapy showed promising results. These early uses of Intraperitoneal injections provide good examples of how the delivery method can be used, and provides a base for future studies on how to properly inject mice for research. Listing a study does not mean it has been evaluated by the U.S. Federal Government. PubMed Rodent (large / mouse) oral (intragastric), intravascular administration (tail vein injection, intraperitoneal injection, intramuscular injection and subcutaneous injection) Intragastric administration and oral taking of non-rodent (dog / monkey) solution and intravenous injection of extremities. PubMed Blood 109, 46274634, doi: 10.1182/blood-2006-12-064345 (2007). RNA was reverse transcribed using the iScript cDNA Synthesis Kit (Bio Rad, Hercules, CA). 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. Intraperitoneal injections may also allow too-rapid entry of bacteria or LPS into the blood. These time-tested therapies may perform well on some patients, but also exhibit inadequacies in efficacy. In vivo clearance of free DiR in healthy mice was showed in Supplemental Figure S4. Gao, J., Dennis, J. E., Muzic, R. F., Lundberg, M. & Caplan, A. I. Blood and marrow stem cell transplants in autoimmune disease. Shamsi M, Sedaghatkish A, Dejam M, Saghafian M, Mohammadi M, Sanati-Nezhad A. Levy, O. et al. Injection Techniques, Restraint, & Handling for Mice and Rats Bull Emerg Trauma. Given the range of potential doses, aiming for an injection volume of 5 l g -1 is advisable. In our study, we found inflamed colon could induce more MSCs engraftment than heathy colon, which partly supported this hypothesis, since inflamed colon has been reported of releasing variety of chemotactic cytokines26. These cells were confirmed as bone marrow MSCs using flow-cytometric analysis and differential identification (Supplementary Figures S1 and S2). was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity . Google Scholar. (A) MSCs were labeled with DiR dye and given by three different ways. The Scheme (Fig. Intraperitoneal Chemotherapy - Memorial Sloan Kettering Cancer Center Gastroenterology 149, 163176 e120, doi: 10.1053/j.gastro.2015.03.013 (2015). Generally, MSCs treatments tend to decrease the pro-inflammatory cytokine (TNF-, IL-6, IL-1b and IFN-) and increase the anti-inflammatory cytokine (IL-10). After intraperitoneal injections, 30% of the female mice died, compared with 3% of the male. Ulcerative colitis (UC) and Crohns disease (CD) are most common conditions in IBD. The peritoneum is a cavity which has been successfully utilized by nephrologists to perform peritoneal dialysis (PD) in patients with renal failure. 2019 Jun 24;36(9):126. doi: 10.1007/s11095-019-2646-z. IP showed better colitis recovery and might be the optimum MSCs delivery route for the treatment of DSS-induced colitis. Afterwards, the samples were incubated with Ki-67 (1:200; Santa Cruz) or FOXP3 (1:100; Antibodies-Online, Aachen, Germany) overnight at 4C. To compare the Ki-67 expression (one of the markers of cell proliferation) among the groups, the colon tissues were collected on day 7 (Fig. An example of how intraperitoneal injections can be optimized is depicted in a study where IP injections are used to deliver anesthesia to mice. Ahmadian Kia, N. et al. A novel intraperitoneal metastatic xenograft mouse model for - PLOS Cochrane Database Syst Rev. and JavaScript. prepared Figure 4. 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. The .gov means its official. PDF EUTHANASIA REFERENCE MANUAL - HumanePro L.Z. Nature biotechnology, doi: 10.1038/nbt.2816 (2014). Unable to load your collection due to an error, Unable to load your delegates due to an error. PDF Recommended Dose Volumes for Common Laboratory Animals - IQ Consortium And the loss of MSCs in the colon may attribute to many reasons, such as, wash out, cell death, or even rejection via the innate immune system. 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. In this study, the intraperitoneal injection was demonstrated as the superior way for MSCs administration in the setting of colitis amelioration. Other gap junction blockers were also occasionally reported to .