The .gov means its official. Proceedings of the National Academy of Sciences of the United States of America 99, 89328937, doi: 10.1073/pnas.132252399 (2002). Google Scholar. 17 The influence of the sex of the animal on anesthetic agents remains poorly researched and understood. For example, if using a dose of 1 U kg -1 , a concentration of 0.2 U ml -1 is suitable. Background Saroglitazar is a novel PPAR-/ agonist with predominant PPAR- activity. Parenteral administration routes include, but are not limited to epidermal, intraarterial, intramuscular (IM and depot IM) , intraperitoneal (IP) , intravenous (IV) , intrastemal injection or infusion techniques, intranasal (inhalation) , intrathecal, injection into the stomach, subcutaneous injections (subcutaneous (SQ and depot SQ . prepared Figure 5. In view of these observations, and the fact that NASH is a Intraperitoneal drug therapy: an advantage - PubMed Journal of immunology (Baltimore, Md. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. X.W., Y.H., Y.N. Inflammatory bowel diseases (IBD) is a broad term that involves chronic inflammation of all or part of the gastrointestinal tract. Other than preformed at the site of injury, MSCs has showed ability to exert their therapeutic effects distally. Distribution of GFP+ MSCs in colon 1 day after injection. Unable to load your collection due to an error, Unable to load your delegates due to an error. Easier to inject that intravenous. Increased initial cell dose ensures an increased number of cells that reach to the injury site. Depletion of O6-alkylguanine-DNA alkyltransferase activity in mammalian 1C). Evid Based Complement Alternat Med. Mice were under intensive observation for 12 days. Histological evaluation was completed in a double-blind fashion by two independent pathologist. Intraperitoneal injections are typically made in the lower right or left quadrant of the hamster's abdomen, not on the midline. Direct injection of sodium pentobarbital (referred to as euthanasia by . Intraperitoneal injections as an alternative method for micro-CT Samples were prepared and tested as previously reported47. Currently, therapy still largely relies on empirical and often implemented in a stepwise fashion: progressing through 5-aminosalicylate compounds, corticosteroids, immunomodulatory drugs and finally anti-TNF drugs7. You are using a browser version with limited support for CSS. Summers, R. W. Novel and future medical management of inflammatory bowel disease. The first major problem with IV route is the pulmonary first-pass effects, which cause significant entrapment of cells15. The complications associated with IP injection are major concern. Exposure to BHT through inhalation, dermal, and oral routes is harmful. 81421003 and No. In order to effectively administer drugs through IP injections, the stomach of the animal is exposed, and the injection is given in the lower abdomen. [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. The levels of immunomodulatory cytokines were compared by real time-PCR and ELISA. If injecting a hazardous substance (biohazard, radiation hazard or chemical hazard), include precautions in the Animal Care Protocol for human safety (e.g. Google Scholar. We notice that the mean density of collagen was lowest in IP group, however, IP group did not exhibit less collagen deposition than the AI group, probably due to the scatter points (Fig. Article [2] Intraperitoneal injections can be similar to oral administration in that hepatic metabolism could occur in both. Influence of Systemic Administration of Coq10 Nanoparticles on Ischemia-Reperfusion Injury on Ovaries in Rat. 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. Intraperitoneal injection or IP injection is the injection of a substance into the peritoneum (body cavity). Establishing a xenograft mouse model of peritoneal dissemination of PDF Chris Quigley Essentials Full Spectrum Curriculum (2023) We next compared serum TSG-6 level in three administration routes at 48h and 72h respectively after MSCs transplantation using ELISA (Fig. Stem cell reviews 10, 127144, doi: 10.1007/s12015-013-9468-x (2014). Fluorescent intensity was quantified and processed using the Living Image Software (Version 4.2; Caliper Life Science). However, doubts exist over the use of Fe 3 O 4-nanoparticles in human beings. 2021 Dec;12(1):8635-8649. doi: 10.1080/21655979.2021.1988364. Cell and tissue research 347, 419427, doi: 10.1007/s00441-011-1306-3 (2012). Injection of substances into peritoneum (body cavity), Current Drugs Delivered Intraperitoneally, "Why i.p. Horwitz, E. M. et al. It was concluded that the intraperitoneal injection had the highest survival rate of 87.5%. Researchers has tried many creative ways to minimize these risks. PubMed Central 8600 Rockville Pike 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. PDF Intraperitoneal (IP) Injection in Rats and Mice SOP 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 . Nature protocols 5, 550560, doi: 10.1038/nprot.2009.238 (2010). Summary. Stem cells and development 21, 21892203, doi: 10.1089/scd.2011.0674 (2012). These findings could be advanced by studying how the route of injection affects the organs in the peritoneal cavity. 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. An improved mouse model of sepsis based on intraperitoneal injections of the enriched culture of cecum slurry . (B) Quantification of % Ki-67+ cells/crypt, the IP and IA>IV>DSS control, n=6 mice/group; n=3 for the control group. Intraperitoneal (ml) Footpad (ml) Mouse <0.1 . In various preclinical models, saroglitazar has been shown to prevent & reverse symptoms of NASH. [11] The effects of this study were the onset of flu-like symptoms, emesis, and abdominal pain. Total RNA was extracted with the RNAeasy Plus kit (QIAGEN). Article In the meantime, to ensure continued support, we are displaying the site without styles This review discusses the usefulness of IP drug therapy and the factors influencing it, as well as strategies to increase the efficacy, and conclude that IP route is an alternate route to the more conventional drug delivery routes, and can be successfully used when the target is within the peritoneal cavity or adjacent tissue. Goncalves Fda, C. et al. Best way for mesenchymal stem cells transplantation for colitis. Levy, O. et al. Intraperitoneal injection or IP injection is the injection of a substance into the peritoneum (body cavity). 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 . Augello, A., Tasso, R., Negrini, S. M., Cancedda, R. & Pennesi, G. Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis. Near-infrared imaging and quantification of MSCs transplants. In study by Pennesi et al., MSCs was found to be able to prevent damages caused by collagen-induced arthritis, despite of lack of a detectable presence in the arthritic joint45. In that same year, a study injected egg whites intraperitoneally into rats to study changes in "droplet" fractions in kidney cells. Two patients with long-standing ulcerative colitis, psoriasis and leukemia underwent allogeneic stem cell transplantation and all the three disorders were in clinical remission for 4 years after transplantation11. With the computer-assisted software, we calculated the density of collagen fibers (%) of all groups. The histological score was defined as the sum of the two parameters (total score=E+I). 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. Stem cells and development 18, 683692, doi: 10.1089/scd.2008.0253 (2009). 6A). 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. Hsiao, S. T. et al. 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 If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. PubMed . Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury. The overall therapeutic factors, MSCs migration and targeting as well as local immunomodulatory cytokines and FoxP3+ cells infiltration were analyzed. 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. Pharm Res. Afterwards, the samples were incubated with Ki-67 (1:200; Santa Cruz) or FOXP3 (1:100; Antibodies-Online, Aachen, Germany) overnight at 4C. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Wang Min, Liang Cong and Hu Hao contributed equally to this work. Histopathological alterations in the mouse brain were detected after SWCNTs exposure. One example is using ultrasound-navigation for puncture. Vilquin, J. T. & Rosset, P. Mesenchymal stem cells in bone and cartilage repair: current status. 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. Select search scope, currently: articles+ all catalog, articles, website, & more in one search; catalog books, media & more in the Stanford Libraries' collections; articles+ journal articles & other e-resources Integrative genetic analysis identifies FLVCR1 as a plasma-membrane Br J Rheumatol 36, 390392 (1997). Article and transmitted securely. They found different source of MSCs with different delivery routes exhibited distinct effects on lung and cardiovascular injury. Horwitz, E. M. et al. showed that incubation of human monoclonal IgG aggregates in plasma for 24 hrs resulted in alteration of the total number of aggregates, led to different aggregate size and changed their . Disease recovery of DSS induced colitis after MSCs injection. The natural history of adult Crohns disease in population-based cohorts. Would you like email updates of new search results? This study was supported by combined grants from the National Natural Science Foundation of China (No. 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. completed the main experiment and wrote the first draft of the paper. Study showed that genetically modified MSCs to increase CXCR-4 expression will lead to an increase of MSCs migration to intestinal with radiation enteritis and then resulted in disease improvement24. Highlighting the importance of choline metabolism . local inflammation and granulomatous reactions at the site of injection, lymph node structural changes, chronic inflammation, skin ulceration, local abscess or tissue sloughing, diffuse systemic . In brief, sections were dewaxed and rehydrated by xylol and acohol. 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). MSCs induced more Ki-67 positive cells in the lower part of the crypt than the DSS control. Intravenous vs intraperitoneal mesenchymal stem cells administration: what is the best route for treating experimental colitis? 2A). 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. Federal law restricts this drug to use by or on the order of a licensed veterinarian. Gynecol Oncol 81, 7781, doi: 10.1006/gyno.2000.6108 (2001). Other gap junction blockers were also occasionally reported to . Second concerning is about the cell dose. Cite this article. Your peritoneal space. Bioengineered. While this route is an easy to master, quick, suitable for chronic treatments and with low impact of stress on laboratory rodents, there is a common concern that it may not be an acceptable route for drug administration in experimental studies. The IP injection significantly inhibited collagen deposition compared with DSS control (P=0.0008) and IV group (P=0.0139). Intratumoral injection of hydrogel-embedded nanoparticles enhances 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. Alavi S, Haeri A, Mahlooji I, Dadashzadeh S. Pharm Res. Samples were frozen and thawed 3 times, centrifuged at 30,000g for 20minutes. Stem cell transplantation showed promising results in IBD management. Intraperitoneal injection of lithium chloride induces lateralized We even tried 1108 cell/mouse in IP and AI group and no immediate death was occurred. MSCs has been well characterized of producing a range of modulatory cytokine, which inspires the designation of these cells as injury drugstore44. At 24h after injection, the intensity of free dye was 100 folds less than the DiR labeled cells (from the bar value. Article Kushnir, C. L., Fleury, A. C., Silver, D. F. & Spirtos, N. M. Intraperitoneal Catheter Placement: The Hammock Technique. [20] There needs to be more research done to determine appropriate dosing and combinations of these drugs to advance intraperitoneal drug delivery. These immune cells may interact with MSCs and exert regulatory functions to MSCs. Influence of Aggregation and Route of Injection on the - PLOS The Ki-67+ cells were greatly increased after MSCs treatment. Intraperitoneal injection is widely used in rodents as a route of drug administration. ADS Cardiovascular research 96, 208209; discussion 210203, doi: 10.1093/cvr/cvs202 (2012). The authors declare no competing financial interests. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in . Ceelen W, Braet H, van Ramshorst G, Willaert W, Remaut K. Expert Opin Drug Deliv. Article After intraperitoneal injections, 30% of the female mice died, compared with 3% of the male. Sci Rep 5, 16760, doi: 10.1038/srep16760 (2015). von Bahr, L. et al. The article overviews whether IP is the best option for euthanization based on evidence associated with welfare implications. After 3 passages, spindle-shaped cell colonies gradually predominate in the cultures. Our findings suggested that IP delivery showed higher MSCs and better experimental colitis recovery, might be an ideal way for MSCs therapy in IBD. Their findings showed that intraperitoneally injected MSCs would form aggregates with macrophages and lymphocytes in peritoneal cavity and remotely secreted TSG-6. For intraperitoneal administration, restrain the mouse with one hand and tilt the head backward to expose the abdomen. 4A,B). Saroglitazar suppresses the hepatocellular carcinoma induced by Internet Explorer). Intraperitoneal (IP) route of drug administration in laboratory animals is a common practice in many in vivo studies of disease models. This study included unilateral SSNHL patients who were hospitalized in our department between . The https:// ensures that you are connecting to the The immunohistochemistry indicated higher repair proliferation (Ki-67) and more FoxP3+ cells accumulation of IP group. Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Intraperitoneal Route of Drug Administration: Should it Be Used in PDF An improved mouse model of sepsis based on intraperitoneal injections 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. Some research showed exogenous CD34 stem cells migration towards the inflamed colon and differentiation into endothelial cells40. . If there is negative pressure, proceed with the injection depress the plunger until the solution has been fully administered. Atreya, R. & Neurath, M. F. Chemokines in inflammatory bowel diseases. Taede et al. Comparative analysis of chemokine receptors expression in mesenchymal stem cells derived from human bone marrow and adipose tissue. Most recently published study by Scaldaferri et al. Histopathological alterations in the mouse brain were detected after . After antigen retrieval, the endogenous peroxidase activity was blocked by 1% H2O2 for 10min. Tuning the Physicochemical Characteristics of Particle-Based Carriers for Intraperitoneal Local Chemotherapy. and H.H. 2020 May 9;12(5):439. doi: 10.3390/pharmaceutics12050439. Injection into egg 1 month 20 doses 1 dose 1 month 1 month Once 3.0 mL/kg 5 mL/kg 10 mL/kg 2.5 mL/kg 1 mL/kg O.^L/g Well tolerated Well tolerated Well tolerated Well tolerated Well tolerated Less mortality 1 \Jg Increase in mortality, decreased activity during righting reflex, running time, visual discrimination, and olfactory aversion test Review article: stem cell therapies for inflammatory bowel disease - efficacy and safety. Filipe et al. was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity . Intraperitoneal Drug Administration - an overview | ScienceDirect Topics Three days after MSCs transplatation, the mice were sacrificed for histological evaluation (H&E and phosphomolibidic acid-picrosirius red staining). The images or other third party material in this article are included in the articles Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. Mice were sacrificed and colons were collected for histological analysis. adult mice at 8-10 weeks of age were first anaesthetized by intraperitoneal injection of 20 mg/ml Avertin (Sigma-Aldrich) (15 l/g . International journal of molecular medicine 37, 115125, doi: 10.3892/ijmm.2015.2413 (2016). Lee et al. volume6, Articlenumber:30696 (2016) They found that PCs can directly migrated from peritoneal cavity and some of them were found at intestinal villi. 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). In addition, the effects of different dosing modalities (e.g., oral administration and intraperitoneal injection) on the . 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. Thus, we have succeeded to produce patient-like tumor colonization of the peritoneal cavity and hepatic metastasis with the human EAC cell line OE19 by intraperitoneal injection in SCID mice. (A) The colonic mRNA expression of TNF- and IL-10 was analyzed by RT-PCR; (B) cytokine contents in colonic protein extracts were determined by ELISA; n=6 mice/group; n=3 for the control group (C) Serum TSG-6 level in different groups measured by ELISA. Intraperitoneal but not intravenous cryopreserved mesenchymal stromal cells home to the inflamed colon and ameliorate experimental colitis. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. IHC was performed according to the standard procedures. The transplanted lymphocytes can produce immunoglobulin (Ig), respond to antigens, and survive for months in this chimeric model (hu-PBL SCID). 2014 Apr 26;(4):CD005284. Blood 122, e23e32, doi: 10.1182/blood-2013-04-495119 (2013). . It also shows how easily substances are absorbed through the peritoneal cavity after an IP injection. All reactions were performed in triplicated. Thus, the aim of the current study was to find out the potential safety range of medical use. Mol Ther 18, 13651372, doi: 10.1038/mt.2010.54 (2010). However, no significant TSG-6 difference was found between AI and IV groups. National Cancer Institute. Blood 118, 330338, doi: 10.1182/blood-2010-12-327353 (2011). Models should begin with local tissue infection, so that bacterial . At the end of laparoscopic . Currently, the intravenous injection (IV) is historically most common methods for MSCs delivery12. Clinical Ovarian and Other Gynecologic Cancer 5, 2426, doi: 10.1016/j.cloc.2011.08.001 (2012). https://doi.org/10.1038/srep30696. Stem cells international 2013, 732742, doi: 10.1155/2013/732742 (2013). Stem Cell Res Ther 3, 51, doi: 10.1186/scrt142 (2012). The site is secure. Dosage: For intravenous (preferred), intracardial, intrapleural, or intraperitoneal injection. In this study, intraperitoneal (IP) injection was used to mimic the human administration route. 2020 Jun 3;37(6):119. doi: 10.1007/s11095-020-02818-8. There are few accounts of the use of intraperitoneal injections prior to 1970. Makhija, S. et al. The Journal of clinical investigation 117, 258269, doi: 10.1172/jci29159 (2007). 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. The provided examples show a variety of uses for intraperitoneal injections in animals for in vitro studies. 2010 May;27(5):735-8. doi: 10.1007/s11095-009-0031-z. Given the range of potential doses, aiming for an injection volume of 5 l g -1 is advisable. In this study, we compared therapeutic efficacy of three MSCs administration routes in DSS-induced colitis. Brown, S. L. et al. Intraperitoneal Versus Interpleural Morphine or Bupivacaine for Pain Zhang, B. et al. In consistence with PCR results, IP groups showed higher IL-10 and lower TNF- than other MSCs delivery ways (Fig. 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. B.X. eCollection 2021. Key points to note. CAS Cancer cell 23, 107120, doi: 10.1016/j.ccr.2012.11.013 (2013). [13] The patient was a 51-year-old male who was hospitalized. A simple method for evaluating dengue vaccine - ScienceDirect Such huge need of MSCs poses a cell source issue, which is a continuing technically and operationally challenge, since most of human ongoing clinical trials use significant less cell dose12.