MSCs induced more Ki-67 positive cells in the lower part of the crypt than the DSS control. Dig Dis 28, 386394, doi: 10.1159/000320392 (2010). Nature biotechnology, doi: 10.1038/nbt.2816 (2014). In addition, even MSCs could formed aggregates in those harsh conditions, there still be a highly risk of self-removal. The immunohistochemistry indicated higher repair proliferation (Ki-67) and more FoxP3+ cells accumulation of IP group. Easier to inject that intravenous. 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. IP, intraperitoneal injection; IV, intravenous injection; AI anal injection; n=68 for treatment group, n=3 for DSS control. After wishing with PBS, the sections were incubated 1h at room temperature with secondary antibody, then visualized by diaminobenzidine (DAB). 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. [16] This study shows how intraperitoneal injections can be more effective and beneficial than other traditional routes of administration. 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. Survival curve plots and Kaplan-Meier analyses were performed using Prism 5.0 software. 2A), which guarantee the less interference from the background signal that coming from free dye. Intraperitoneal injection or IP injection is the injection of a substance into the peritoneum (body cavity). An improved mouse model of sepsis based on intraperitoneal injections of the enriched culture of cecum slurry . A disadvantage of using intraperitoneal injections is that they can have a large variability in effectiveness and misinjection. Additionally, the clinical translation is another concern. [citation needed], In humans, the method is widely used to administer chemotherapy drugs to treat some cancers, particularly ovarian cancer. Injections are given along the midline caudal to the umbilicus or low on the right lateral abdomen. Hsiao, S. T. et al. Gastroenterology 145, 158165 e152, doi: 10.1053/j.gastro.2013.04.007 (2013). IP injection showed better amelioration of colitis and may be an ideal delivery way for MSCs in IBD therapy. Comparative analysis of chemokine receptors expression in mesenchymal stem cells derived from human bone marrow and adipose tissue. query serum metabolite genome-wide association study (GWAS) data to identify an association between choline metabolism and feline leukemia virus subgroup C cellular receptor 1 (FLVCR1). 4 The scalp was disinfected and a midline incision was made in the skin. But how these miracle cells reach to the lumen and by which possible migration route? A study was conducted to determine the best route of administration to transplant mesenchymal stem cells for colitis. CBSKL2015Z01 and CBSKL2015Z12), PLA 12th Five-Year Program (BSW11J013) and National Science and Technology Major Project (No. Several medications such as antibiotics are given via the intraperitoneal (IP) route in PD patients to treat episodes of peritonitis. 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 . [6] In 1968, melatonin was delivered to rats intraperitoneally in order to study how brain serotonin would be affected in the midbrain. Transplantation proceedings 39, 573576, doi: 10.1016/j.transproceed.2006.12.019 (2007). injection, or EBI) remains the most humane method available. After antigen retrieval, the endogenous peroxidase activity was blocked by 1% H2O2 for 10min. 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. 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. Intraperitoneal Drug Administration - an overview | ScienceDirect Topics MSCs has been found to directly differentiate into end-stage cells to augment bone damages and repair cartilage defects38,39. Many published studies have showed the benefits of IV delivery in IBD treatment. Best way for mesenchymal stem cells transplantation for colitis. 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. Li, Y. P. et al. CAS These time-tested therapies may perform well on some patients, but also exhibit inadequacies in efficacy. 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. Castelo-Branco, M. T. et al. Best way for mesenchymal stem cells transplantation for colitis. Ng, S. C. et al. The transplanted lymphocytes can produce immunoglobulin (Ig), respond to antigens, and survive for months in this chimeric model (hu-PBL SCID). Upon intravenous and intraperitoneal injection of stressed MSA, fluorescent "hotspots" were observed in the spleens, livers and lungs. However, whether the lymphocytes actually . Intraperitoneal drug therapy: an advantage - PubMed Clinical Announcement: Intraperitoneal chemo-therapy for ovarian cancer. 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. As mentioned above, a commonly used cell dose is 1106 cells/30g mouse, which would be equivalent to 33106/kg or approximately 2.3billion cells for a 70kg adult. 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. During the observation, the body weight changes and fecal blood and their survival date was faithfully record. Clinical use of bone marrow, bone marrow concentrate and expanded bone marrow mesenchymal stem cells in cartilage disease. A simple method for evaluating dengue vaccine - ScienceDirect All fluorescent imaging procedures were conducted on small animal imaging system (IVIS Kinetics; Caliper Life Science). Scientific Reports (Sci Rep) The Journal of infectious diseases 198, 456464, doi: 10.1086/590112 (2008). PubMed Samples were prepared and tested as previously reported47. Slider with three articles shown per slide. 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. If there is negative pressure, proceed with the injection depress the plunger until the solution has been fully administered. 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. Histological evaluation was completed in a double-blind fashion by two independent pathologist. 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 For example, if using a dose of 1 U kg -1 , a concentration of 0.2 U ml -1 is suitable. Listing a study does not mean it has been evaluated by the U.S. Federal Government. In DSS control FoxP3 positive cells only accounted for 1.51% of total cells, while the IP group showed 13.5% positive cells (P<0.001). prepared Figure 4. Intraperitoneal injection of lithium chloride induces lateralized 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. Changing Crohns disease management: need for new goals and indices to prevent disability and improve quality of life. 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 results of this IP injection were the disappearance of the ascites associated with the rupture. 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. iQ SYBR Green Supermix and CFX96 (Bio-Rad) were used for template amplification with a primer for each of the transcripts examined. 1A) showed the time point of DSS given and MSCs therapy. Stem cells (Dayton, Ohio) 26, 279289, doi: 10.1634/stemcells.2007-0454 (2008). They are mitomycin C, cisplatin, carboplatin, oxaliplatin, irinotecan, 5-fluorouracil, gemcitabine, paclitaxel, docetaxel, doxorubicin, premetrexed, and melphalan. 2, Haidian District, Beijing 100193, China. PubMed Central . & Gratwohl, A. After 3 passages, spindle-shaped cell colonies gradually predominate in the cultures. DiR-labeled cells were injected into DSS mice by three different ways. You are using a browser version with limited support for CSS. Article PubMedGoogle Scholar. In vivo clearance of free DiR in healthy mice was showed in Supplemental Figure S4. [11] The effects of this study were the onset of flu-like symptoms, emesis, and abdominal pain. Some research showed exogenous CD34 stem cells migration towards the inflamed colon and differentiation into endothelial cells40. . Bookshelf The latter is . In addition, IP showed more intense Ki-67 stain in bottom of the crypt, which suggested more active mucosa repair proliferation (Fig. 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). Mouse insulin gradually decreased and was no more detectable 13 weeks after STZ injection. Metabolite tracing, radioactive uptake experiments, and CRISPR screens demonstrate that FLVCR1 is the major plasma-membrane choline transporter. Treatment of dextran sodium sulfate-induced experimental colitis by adoptive transfer of peritoneal cells. The following approaches are novel, and require further testing in humans before being accepted as potential treatment options: The IP injection significantly inhibited collagen deposition compared with DSS control (P=0.0008) and IV group (P=0.0139). J Vis Exp, doi: 10.3791/1488 (2010). 4D,E). intraarticular and intraperitoneal use of opioids, pain management in the emergency room and in the intensive care unit, pain management issues during pregnancy, geriatric pain, and hospice care and end-of-life issues. L.Z. 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. [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. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Depletion of O6-alkylguanine-DNA alkyltransferase activity in mammalian Understanding when intraperitoneal injections can be utilized and in what applications is beneficial to advance current drug delivery methods and provide avenues for further research. On the contrary, the anti-inflammatory IL-10 level were substantially elevated in IP group compared with the IV group and DSS control, but the inter-group difference between IP and AI group, AI and IV group were not identified. [2] Intraperitoneal injections can be similar to oral administration in that hepatic metabolism could occur in both. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. Inflammatory bowel disease (IBD). Cosnes, J., Gower-Rousseau, C., Seksik, P. & Cortot, A. Stem cells and development 21, 21892203, doi: 10.1089/scd.2011.0674 (2012). Google Scholar. Insular cortex is a critical brain region that participates in the interoceptive sensations. 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. Collagen deposition limits immune reconstitution in the gut. Though IP injection showed benefits in many human and animal . ADS The peritoneal micromilieu commits B cells to home to body cavities and the small intestine. But for the IP injection, because of more cell accumulation in the inflamed colon, less initial cells might reach minimum effective cell dose. This site needs JavaScript to work properly. 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 & Dennis, J. E. MSCs: Delivery Routes and Engraftment, Cell-Targeting Strategies and Immune Modulation. 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). Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Experiments with microspheres has showed that most of particle of this size would be clear out by the lung17. CAS In quantification study, the intensity of engrafted cells in IP and AI groups were significant higher than the IV (P=0.004, P=0.0012; Fig. Abstract Intraperitoneal (IP) injection is frequently reported to be as effective as intravenous (IV) injection. 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. [13] The patient was a 51-year-old male who was hospitalized. Intraperitoneal Injection - an overview | ScienceDirect Topics In brief, sections were dewaxed and rehydrated by xylol and acohol. IP injections are used for a variety of reasons: The peritoneum provides a large surface area for absorption of drug (compared with intramuscular (IM) or subcutaneous); can thus inject a larger fluid volume. GTTs and ITTs in mice: simple tests, complex answers - Nature Article 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]. Ko, I. K. et al. Nature medicine 18, 618623, doi: 10.1038/nm.2695 (2012). Macrophage Reverse Cholesterol Transport | Circulation Shamsi M, Sedaghatkish A, Dejam M, Saghafian M, Mohammadi M, Sanati-Nezhad A. Stem Cell Res Ther 3, 51, doi: 10.1186/scrt142 (2012). 2020 May 9;12(5):439. doi: 10.3390/pharmaceutics12050439. By submitting a comment you agree to abide by our Terms and Community 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. 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). Intraperitoneal injection is not always a suitable alternative to Two early reports aroused the global interests of stem cell transplantation in IBD management. 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. 107vs. 109 ; Fig. 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). Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation and development of colitis-associated cancer. 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. therapy cannot yet be considered as a standard of care for the first-line treatment of ovarian cancer: a systematic review", "Review of intraperitoneal injection of sodium pentobarbital as a method of euthanasia in laboratory rodents", "Changes in "droplet" fractions from rat kidney cells after intraperitoneal injection of egg white", "Errors Related to Different Techniques of Intraperitoneal Injection in Mice", "Postoperative pain after abdominal hysterectomy: a randomized, double-blind, controlled trial comparing continuous infusion vs patient-controlled intraperitoneal injection of local anaesthetic", "Cannabinoid Disposition After Human Intraperitoneal Use: An Insight Into Intraperitoneal Pharmacokinetic Properties in Metastatic Cancer", "Intraperitoneal Route of Drug Administration: Should it Be Used in Experimental Animal Studies? Intraperitoneal Injection of Oncolytic Viruses H101 for Patients With Refractory Malignant Ascites. . Intraperitoneal injection (IP), Intravenous injection (IV) or anal injection (AI)? Overall, many studies utilize IP injections to deliver therapeutics to lab animals due to the efficiency of the administration route. While the DiR labeled cells showed very different cell distribution. It was determined that IP injections are a good option for Fenestra to quantify liver tumors in mice. Further study demonstrated TSG-6 alone was sufficient to reduce intestinal inflammation in mice with colitis. B.X. 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. Hepatic and renal . MeSH Disclaimer. Gao, J., Dennis, J. E., Muzic, R. F., Lundberg, M. & Caplan, A. I. Mice were sacrificed and colons were collected for histological analysis. 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. In addition, fewer female mice achieved surgical anesthesia, suggesting a narrow therapeutic window for intraperitoneal KX in female mice. In our study, we tracked the GFP+ MSCs colon colonization, but our results also showed the short stay of MSCs after injection. Although controversial, intraperitoneal use in ovarian cancer has been recommended as a standard of care. PubMed Lu, Z., Wang, J., Wientjes, M. G. & Au, J. L. Intraperitoneal therapy for peritoneal cancer. Bull Emerg Trauma. A . Kalchenko, V. et al. PubMed (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. At 24h after injection, the intensity of free dye was 100 folds less than the DiR labeled cells (from the bar value. More recently the IP route has been used for chemotherapy in patients with intra-abdominal malignancies, i.e. Brown, S. L. et al. ADS The primer sequences used were listed in Supplementary Table S1. Subcutaneous Compared with Intraperitoneal Ketamine-Xylazine for Zhang, J., Gong, J. F., Zhang, W., Zhu, W. M. & Li, J. S. Effects of transplanted bone marrow mesenchymal stem cells on the irradiated intestine of mice. Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5(+) stem cell. The fate of human peripheral blood lymphocytes after - PubMed Krampera, M. et al. Histopathological comparison of colitis after 3 days MSCs delivery. This is really an interesting finding, however exact mechanisms are still unknown. 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.
