intraperitoneal injection in humans

PubMed seem to have found the key drug of MSCs in the treatment of colitis, TSG-647. Given the range of potential doses, aiming for an injection volume of 5 l g -1 is advisable. Injections Intraperitoneal (IP) "Mouse" Once animal is restrained turn over so abdomen is exposed. We believe with the increasing interests for IP injection in the field of cytotherapy, more innovation and creative ideas for reducing IP complications will come up. 1B). Zhu, H. et al. These time-tested therapies may perform well on some patients, but also exhibit inadequacies in efficacy. Many published studies have showed the benefits of IV delivery in IBD treatment. [10] The results depicted that ketobemidone consumption was significantly lower when patients controlled anesthetic through IP. This inconsistency may attributed to different MSCs types. All reactions were performed in triplicated. This work is licensed under a Creative Commons Attribution 4.0 International License. IHC was performed according to the standard procedures. Google Scholar. Karp, J. M. & Leng Teo, G. S. Mesenchymal stem cell homing: the devil is in the details. Stem cells and development 21, 21892203, doi: 10.1089/scd.2011.0674 (2012). During the observation, the body weight changes and fecal blood and their survival date was faithfully record. Increased initial cell dose ensures an increased number of cells that reach to the injury site. All fluorescent imaging procedures were conducted on small animal imaging system (IVIS Kinetics; Caliper Life Science). You are using a browser version with limited support for CSS. Kalchenko, V. et al. Ankrum, J. This is really an interesting finding, however exact mechanisms are still unknown. However, whether the lymphocytes actually . Kyriakou, C., Rabin, N., Pizzey, A., Nathwani, A. More recently the IP route has been used for chemotherapy in patients with intra-abdominal malignancies, i.e. Comparative analysis of chemokine receptors expression in mesenchymal stem cells derived from human bone marrow and adipose tissue. However, doubts exist over the use of Fe 3 O 4-nanoparticles in human beings. Then, the bone marrow was flushed out with 1mL syringe. The expression level of TNF-, the most important pro-inflammatory cytokine, was markedly decreased in IP group, compared with AI (P=0.0174), IV (P=0.0019) and control group (P<0.001), respectively. MPO activity per gram of wet tissue was calculated as: MPO activity (U/g wet tissue)=(A450) (13.5)/tissue weight (g). GFP+ cells were detected at the inflamed colon. Clinical use of bone marrow, bone marrow concentrate and expanded bone marrow mesenchymal stem cells in cartilage disease. It was determined that IP injections are a good option for Fenestra to quantify liver tumors in mice. Lee et al. 81421003 and No. Novel mechanism for mesenchymal stem cells in attenuating peritoneal adhesion: accumulating in the lung and secreting tumor necrosis factor alpha-stimulating gene-6. Complications associated with intraperitoneal chemotherapy catheters. Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population. Your peritoneal space. In addition, even MSCs could formed aggregates in those harsh conditions, there still be a highly risk of self-removal. 2019 Jun 24;36(9):126. doi: 10.1007/s11095-019-2646-z. ISSN 2045-2322 (online). 2014ZX09508002). Humans Injections, Intraperitoneal Peritoneal Cavity* / blood supply Peritoneal Neoplasms / drug therapy Peritonitis / drug therapy Substances Anti-Bacterial Agents Antineoplastic Agents . 107vs. 109 ; Fig. DSS only served as control. In this study, three different MSCs delivery routes, intraperitoneal injection (IP), intravenous injection (IV) and anal injection (AI) were compared on DSS-induced colitis mouse model. Disclaimer. Therefore, the biological differences of different source MSCs should be considered systematically when interpreting the research results and choosing for specific clinical application. In IP group, cells were found accumulation at the epithelium; In AI group, cells were mainly in the lumen; In IV group, cells were fewer and located in lamina propria. 2014 Apr 26;(4):CD005284. 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. 5B). Journal of biomedical optics 11, 050507, doi: 10.1117/1.2364903 (2006). The Ki-67+ cells were greatly increased after MSCs treatment. Stem cells and development 18, 683692, doi: 10.1089/scd.2008.0253 (2009). Article Liang, J. et al. Epub 2020 Mar 18. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Comparison of molecular profiles of human mesenchymal stem cells derived from bone marrow, umbilical cord blood, placenta and adipose tissue. PubMedGoogle Scholar. Horizontal bars represent medians, boxes represent the 25th and 75th percentiles. ADS Accessibility Language links are at the top of the page across from the title. Article CAS 2010 May;27(5):735-8. doi: 10.1007/s11095-009-0031-z. CAS Choi, H., Lee, R. H., Bazhanov, N., Oh, J. Y. J Vis Exp, doi: 10.3791/1488 (2010). Intraperitoneal administration allows quick reabsorption of large volumes of substances and is the preferred injection route for nonirritant, isotonic solutions [7,11]. Three days after MSCs transplatation, the mice were sacrificed for histological evaluation (H&E and phosphomolibidic acid-picrosirius red staining). ADS [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. IP injections were suitable for serial imaging as well as imaging mice at multiple time points, which would be ideal for longitudinal drug treatment experiments. We also evaluated serum TSG-6 in three MSCs administration route. Google Scholar. Intraperitoneal injections are a way to administer therapeutics and drugs through a peritoneal route (body cavity). 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. PubMed 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. Intravenous vs intraperitoneal mesenchymal stem cells administration: what is the best route for treating experimental colitis? Mouse insulin gradually decreased and was no more detectable 13 weeks after STZ injection. Here, three different MSCs delivery routes: intraperitoneal (IP), intravenous (IV) and anal injection (AI) were compared on DSS-induced colitic mice model. After 5 days of DSS contained water, all the subject mice showed strong positive test of fecal occult blood. FOIA Estes, J. et al. Evid Based Complement Alternat Med. Figure 1. Dosage: For intravenous (preferred), intracardial, intrapleural, or intraperitoneal injection. Yui, S. et al. Caplan, A. I. official website and that any information you provide is encrypted Interestingly, in some IP injection mice, GFP+ cells were observed in the epithelium of the inflamed colon. CAS Firstly, peritoneal cavity provides an isolated, hemodynamically stable, sterile and nutritious environment with enough growth spaces, which are very critical factors for aggregates forming. Please enable it to take advantage of the complete set of features! Intraperitoneal injection carries the risk of causing internal injury or of misplaced injection into a blood vessel or an organ, particularly the large thin-walled cecum or urinary bladder. MSCs has been well characterized of producing a range of modulatory cytokine, which inspires the designation of these cells as injury drugstore44. adult mice at 8-10 weeks of age were first anaesthetized by intraperitoneal injection of 20 mg/ml Avertin (Sigma-Aldrich) (15 l/g . -Lactalbumin is an example of a "retired" self-protein because its expression in normal . Bull Emerg Trauma. [7] In 1969, errors depending on a variety of techniques of administering IP injections were analyzed, and a 12% error in placement was found when using a one-man procedure versus a 1.2% error when using a two-man procedure. 4D,E). HHS Vulnerability Disclosure, Help IP, intraperitoneal injection; IV, intravenous injection; AI anal injection; n=68 for treatment group, n=3 for DSS control. Every 1107 cells were incubated with 10mL DiR solution (PBS based containing 3.5g/mL dye and 0.5% ethanol) for 30min at 37C. (B) Quantification of % Ki-67+ cells/crypt, the IP and IA>IV>DSS control, n=6 mice/group; n=3 for the control group. The study showed that the number of small droplets decreased after administration of the egg whites, indicating that they have been changed to large droplets. Cancer cell 23, 107120, doi: 10.1016/j.ccr.2012.11.013 (2013). MeSH Additionally, the clinical translation is another concern. PubMed Colonic mRNA expression of inflammatory mediators such as TNF-, IL-6, IL-1, IL-10 and IFN- were analyzed by real time-PCR in order to evaluate the local inflammatory environment (Fig). Normal mouse IgG was used as a substitute for the primary antibody as negative control. Haematologica 93, 14571465, doi: 10.3324/haematol.12553 (2008). A human study showed that after injection of HDL labeled with a CE tracer, most of the tracer that was ultimately found in the bile arrived there after transfer to apoB-containing lipoproteins, . All the tissue sections in this study were scan and analyzed with Virtual slide scanning system (VS120-S, Olympus). MSCs also showed ability to promote epithelial repair54 and regulate dendritic cells by cell-cell contact mechanism55,56. gynecological and gastrointestinal cancers and has shown very promising results. 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 . Sirius red staining showed disorganized collagen fibers in DSS control colon, which were diffusely distributed in the injured colon wall. 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). Mice were under intensive observation for 12 days. A consensus report written on behalf of the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT). Generally, the mice were killed by cervical dislocation. . After centrifuge, the cells were certificated and transferred to MSC expansion culture medium consisting of a-minimum essential medium (a-MEM; Gibco, USA) supplemented with 10% fetal bovine serum (FBS; Gibco, USA) and 100g/mL penicillin/streptomycin. Article [3] The study however did not find an increase in conception rate when compared to mating. We next compared serum TSG-6 level in three administration routes at 48h and 72h respectively after MSCs transplantation using ELISA (Fig. Stem cells (Dayton, Ohio) 30, 15751578, doi: 10.1002/stem.1118 (2012). analyzed the data, J.L. Intraperitoneal foreign bodies such as suture material, clips, and mesh also contribute to adhesion formation. However, they found the migrated PCs was very few and these may attribute to: 1) the recipient are heathy rat. Intraperitoneal injection of 0.5-14.6 mg/kg 17- or 37-nm gold to mice produced an increase of brain dopamine, . Blood 109, 46274634, doi: 10.1182/blood-2006-12-064345 (2007). From the overall appearance, the hyperemia and edema of the colon in all MSCs treatment groups became milder than the DSS control. This led to the patients being able to be discharged earlier than when anesthesia was administered continuously. Kenny et al. By systemic evaluation of epithelium and lymphocyte infiltration, the IP injection group showed the relatively lower severity score compared with AI group (P=0.034) and IV (P=0.002), respectively. Article Cell stem cell 5, 5463, doi: 10.1016/j.stem.2009.05.003 (2009). By using this techniques, the catheter complications, in particular obstruction, bowel and vaginal cuff perforation were greatly reduced61. Furthermore, the body weight changes displayed the less weight loss and quick weight gain of IP injection group and the maximum group difference among was reached on day 3 (Fig. Afterwards, the samples were incubated with Ki-67 (1:200; Santa Cruz) or FOXP3 (1:100; Antibodies-Online, Aachen, Germany) overnight at 4C. These two kinds of MSCs differ in proliferation rates and differentiation capacities as well as show significant difference in cytokine secretome and chemokine receptor expression which may affect migration, engraft and even local function32,33,34,35,36. [citation needed], In humans, the method is widely used to administer chemotherapy drugs to treat some cancers, particularly ovarian cancer. 5C). Stem Cells 29, 15721579, doi: 10.1002/stem.708 (2011). Growth hormone After 3 passages, spindle-shaped cell colonies gradually predominate in the cultures. For example, discharged accompany with stool or cleared out by lung microphage. 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. DiR-labeled cells were injected into DSS mice by three different ways. In this study, intraperitoneal (IP) injection was used to mimic the human administration route. One example is using ultrasound-navigation for puncture. Ng, S. C. et al. Another study by coating MSCs with VCAM-1 also exhibited an increased MSCs migration to the inflamed colon and promoted tissue repair capacity25. M.W., C.L. These immune cells may interact with MSCs and exert regulatory functions to MSCs. . 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. Thus, the aim of the current study was to find out the potential safety range of medical use. Human. Female nude mice (Envigo) were anesthetized by intraperitoneal (IP) injection of ketamine/xylazine and immobilized in a stereotactic frame (Stoelting). Google Scholar. Intraperitoneal injection or IP injection is the injection of a substance into the peritoneum (body cavity). In vivo clearance of free DiR in healthy mice was showed in Supplemental Figure S4. Google Scholar. It means IP injection is more feasible and reasonable for clinical settings. 4 The scalp was disinfected and a midline incision was made in the skin. [16] This study shows how intraperitoneal injections can be more effective and beneficial than other traditional routes of administration. PloS one 7, e33360, doi: 10.1371/journal.pone.0033360 (2012). Exposure to BHT through inhalation, dermal, and oral routes is harmful. The optimum route of administration is an importance clinical issue not only for chemical drug, but also for stem cytotherapy. In contrast, MSCs were either infused with the bowel waste (for AI route) or trapped in lung/liver vessels (for IV route)51, where aggregates forming would be affected by unfavorable conditions, such as contaminated microenviroment, limited growth space and hemodynamically unstable in lung/liver vessels. The problem is obvious, the solution is not: numbers do matter in cardiac cell therapy! n=3. PubMed Central Ceelen W, Braet H, van Ramshorst G, Willaert W, Remaut K. Expert Opin Drug Deliv. Pull back on the plunger to ensure negative pressure prior to injecting. Available at: http://www.cdc.gov/ibd/ (Accessed: 7th April 2016) (2014). Article Rep. 6, 30696; doi: 10.1038/srep30696 (2016). An official website of the United States government. Collagen deposition limits immune reconstitution in the gut. (A) Representative IHC images of each treatment group. In our study, we tracked the GFP+ MSCs colon colonization, but our results also showed the short stay of MSCs after injection. The MSCs may exert their therapeutic effects on mainly three following aspects: firstly, to differentiate and replace the damage tissue; secondly, to secrete soluble immunomodulatory bioactive molecules and establish a regenerative milieu; thirdly, cell-to-cell contact and interaction with immune cells. Filipe et al. Stem cell transplantation showed promising results in IBD management. The ELISA kit for TNFinduced protein 6 was used (CUSABIO Life science, China). In 1996, intraperitoneal (IP) administration of cisplatin plus intravenous (IV) cyclophosphamide proved superior to both drugs given intravenously at the same doses-which, at the time, was the standard treatment in the United States. 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. The accessibility of the therapeutic cells to their expectable target site is strongly dependent on the route of administration used. Taede et al. 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. n=68 mice/group; n=3 for the control and naive (health mice) group. 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). iQ SYBR Green Supermix and CFX96 (Bio-Rad) were used for template amplification with a primer for each of the transcripts examined. Injection of substances into peritoneum (body cavity), Current Drugs Delivered Intraperitoneally, "Why i.p. Best way for mesenchymal stem cells transplantation for colitis. Truncal blocks and neuraxial . Wang Min, Liang Cong and Hu Hao contributed equally to this work. Surg Clin North Am 87, 727741, doi: 10.1016/j.suc.2007.03.004 (2007). They found that PCs can directly migrated from peritoneal cavity and some of them were found at intestinal villi. Shamsi M, Sedaghatkish A, Dejam M, Saghafian M, Mohammadi M, Sanati-Nezhad A. The complications associated with IP injection are major concern. Reduced MPO activities were identified in all MSCs groups, of which IP injection showed lower MPO activity (P=0.001vs. IV and P=0.0158vs. AI; Fig. Future Oncol 6, 16251641, doi: 10.2217/fon.10.100 (2010). FoxP3+ cells were greatly increased in MSCs therapy. Intraperitoneal chemotherapy for peritoneal metastases: an expert opinion. Mice were maintained in a light/temperature-controlled room and allowed to freely access to chow diet and water. Highlighting the importance of choline metabolism . Comparison of colonic inflammatory cytokine TNF- and IL-10 at day 3. Mice are usu Lopez-Cubero, S. O., Sullivan, K. M. & McDonald, G. B. National Library of Medicine The three groups can decrease the mortality rate compared with PBS control, however, the IP injection showed the highest survival rate of 87.5% (P=0.0021vs. Control, Fig. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Further study demonstrated TSG-6 alone was sufficient to reduce intestinal inflammation in mice with colitis. The IP injection showed longer colon, with mean length of 8.24cm compared with 6.90cm in AI group (P=0.0057) and 6.14cm in IV group (P<0.001; Fig. humans have been associated with clinical pain, inflammatory lesions, and abscess formation in . Since the IP injection induced more cells migration to the inflamed colon, we further compared the difference in mucosa healing of different delivery routes. Alavi S, Haeri A, Mahlooji I, Dadashzadeh S. Pharm Res. Mice were sacrificed and colons were collected for histological analysis. In addition, fewer female mice achieved surgical anesthesia, suggesting a narrow therapeutic window for intraperitoneal KX in female mice. It is estimated that as many as 1.4million Americans and 2.4million Europeans are suffering from these diseases1,2. A., Ong, J. F. & Karp, J. M. Mesenchymal stem cells: immune evasive, not immune privileged. MathSciNet Distribution of GFP+ MSCs in colon 1 day after injection. The Journal of clinical investigation 117, 258269, doi: 10.1172/jci29159 (2007). However, is IV injection the best way for MSCs delivery in IBD? Intraperitoneal injections are the preferred method of administration in many experimental studies due to the quick onset of effects post injection. Heo, J. S., Choi, Y., Kim, H. S. & Kim, H. O. It was concluded in a review article that utilizing IP injections to administer drugs to laboratory rodents in experimental studies is acceptable when being applied to proof-of-concept studies.[15]. Gut 63, 588597, doi: 10.1136/gutjnl-2013-304636 (2014). Wang, N. et al. [19] It was concluded that IP administration should not be used over intravenous therapy due to high radiation absorption in the intestines. With the computer-assisted software, we calculated the density of collagen fibers (%) of all groups. Cells, tissues, organs 169, 1220 (2001). Intraperitoneal (IP) Injection (Injection of Sodium Pentobarbital . Internet Explorer). Federal government websites often end in .gov or .mil. ***P<0.001; **P<0.01. This case presents the question of how THC is absorbed in the peritoneal cavity. Solid lipid nanoparticle delivery of rhynchophylline enhanced the efficiency of allergic asthma treatment via the upregulation of suppressor of cytokine signaling 1 by repressing the p38 signaling pathway. (A) Scheme of the treatment, the day of MSCs injection was defined as day 0. Intraperitoneal injection (IP), Intravenous injection (IV) or anal injection (AI)? Monitor chest movements to make sure the animal is doing ok. On the mouse you want to make your IP injection in the lower right or left quadrant of abdomen trying to avoid hitting bladder, liver, or other internal organs. Tests were read by an independent observer (Cong Liang) and scored 05 as shown by the color indicators provided by the manufacturer. was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity . 2018 Nov;25(1):846-861. doi: 10.1080/10717544.2018.1455764. completed the main experiment and wrote the first draft of the paper. Google Scholar. 2B). Google Scholar. Effects of different mesenchymal stromal cell sources and delivery routes in experimental emphysema. Article Here, we combined the iDISCO + method and Fos immunostaining to confirm that the middle part of the right-side, but not the left-side, insular cortex in adult male mice is activated by intraperitoneal injection of lithium chloride. DiR labeling showed no harm to the MSCs viability13 (Supplementary Figure S3). Intraperitoneal injection is widely used in rodents as a route of drug administration. IP injected human MSC rapidly formed aggregates with mouse macrophages and B220+ lymphocytes and attached to the walls of the peritoneal cavity. [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. Gao, J., Dennis, J. E., Muzic, R. F., Lundberg, M. & Caplan, A. I. Collagen Deposition was assessed with phosphomolibidic acid-picrosirius red staining. Vishnubalaji, R., Al-Nbaheen, M., Kadalmani, B., Aldahmash, A. In various preclinical models, saroglitazar has been shown to prevent & reverse symptoms of NASH. This allows researchers to observe the effects of a drug in a shorter period of time, and allows them to study the effects of drugs on multiple organs that are in the peritoneal cavity at once. Drug Deliv. Pentobarbital sodium Injection Caution. Antunes, M. A. et al. study on peritoneal cells (PCs) migration to gut may give us some hints27. Easier to inject that intravenous. Collagen deposition is another indicator for wound healing, however, extensive collagen deposition may hamper the gut reconstitution14. Supplies: Inflammatory bowel diseases (IBD) is a broad term that involves chronic inflammation of all or part of the gastrointestinal tract. Shariati M, Zhang H, Van de Sande L, Descamps B, Vanhove C, Willaert W, Ceelen W, De Smedt SC, Remaut K. Pharm Res. Another example of how intraperitoneal injections are used in studies involving rodents is the use of IP for micro-CT contrast enhanced detection of liver tumors. In 2018, a patient with stage IV ovarian cancer and peritoneal metastases was injected intraperitoneally with 12g of mixed cannabinoid before later being hospitalized. 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. Clipboard, Search History, and several other advanced features are temporarily unavailable. Google Scholar. This study compared intraperitoneal injections, intravenous injections, and anal injections. Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation. The need of intestinal resection in CD has remained stable8 and the colectomy rates in UC were still for 20% and 30% within 10 and 25 years of diseases duration9. Disease recovery of DSS induced colitis after MSCs injection. (C) Percentage of body weight changes over time. Tyndall, A. There is a little fluid in between the peritoneal lining and your organs. Incidence and phenotype of inflammatory bowel disease based on results from the Asia-pacific Crohns and colitis epidemiology study. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. 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). ADS Listing a study does not mean it has been evaluated by the U.S. Federal Government. 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. In a case of a ruptured hepatocellular carcinoma, it was reported that the patient was treated successfully through the use of an intraperitoneal injection of OK-432, which is an immunomodulatory agent. They are mitomycin C, cisplatin, carboplatin, oxaliplatin, irinotecan, 5-fluorouracil, gemcitabine, paclitaxel, docetaxel, doxorubicin, premetrexed, and melphalan. After wishing with PBS, the sections were incubated 1h at room temperature with secondary antibody, then visualized by diaminobenzidine (DAB). Hsiao, S. T. et al. Ballinger AE, Palmer SC, Wiggins KJ, Craig JC, Johnson DW, Cross NB, Strippoli GF. The levels of immunomodulatory cytokines were compared by real time-PCR and ELISA. 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. Oakland Coliseum View From My Seat, How To Beat Thoron Skyrim, Articles I