PDF An improved mouse model of sepsis based on intraperitoneal injections Intraperitoneal Injection Is Not a Suitable Administration Route for We also evaluated serum TSG-6 in three MSCs administration route. In our study, we tracked the GFP+ MSCs colon colonization, but our results also showed the short stay of MSCs after injection. Peyrin-Biroulet, L., Loftus, E. V. Jr., Colombel, J. F. & Sandborn, W. J. (B) Quantification of % Ki-67+ cells/crypt, the IP and IA>IV>DSS control, n=6 mice/group; n=3 for the control group. Because labeled cells are founded in Peyers patch of the gut and peripheral blood, they proposed the most likely routes might be by both lymph- and blood circulation. Influence of Aggregation and Route of Injection on the - PLOS 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. However, more studies described MSCs as hit and run therapy, which discovered most of MSCs died and cleared from the body within 48 to 72h20,41,42,43. Stem Cell Res Ther 3, 51, doi: 10.1186/scrt142 (2012). Intraperitoneal chemotherapy for peritoneal metastases: an expert opinion. Berberich, S., Forster, R. & Pabst, O. Researchers has tried many creative ways to minimize these risks. Acceptable Method (s) Injected barbiturates and barbiturate combinations. If there is negative pressure, proceed with the injection depress the plunger until the solution has been fully administered. By using this techniques, the catheter complications, in particular obstruction, bowel and vaginal cuff perforation were greatly reduced61. . Intraperitoneal injection (IP), Intravenous injection (IV) or anal [1] Fluids are injected intraperitoneally in infants, also used for peritoneal dialysis. MSCs organ distribution and engraftment was analyzed and quantified by GFP+ MSCs as well as Near-infrared fluorescence imaging. Liang, J. et al. Stem cells (Dayton, Ohio) 26, 279289, doi: 10.1634/stemcells.2007-0454 (2008). Intraperitoneal Injection - an overview | ScienceDirect Topics 2A), which guarantee the less interference from the background signal that coming from free dye. Upon intravenous and intraperitoneal injection of stressed MSA, fluorescent "hotspots" were observed in the spleens, livers and lungs. The problem is obvious, the solution is not: numbers do matter in cardiac cell therapy! ADS Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury. The holder retains the arms of the animal and tilts the head lower than the abdomen to create optimal space in the peritoneal cavity. Ballinger AE, Palmer SC, Wiggins KJ, Craig JC, Johnson DW, Cross NB, Strippoli GF. gynecological and gastrointestinal cancers and has shown very promising results. Ulcerative colitis (UC) and Crohns disease (CD) are most common conditions in IBD. Google Scholar. Drug delivery systems for intraperitoneal therapy. Though IP injection showed benefits in many human and animal . some potent chemo and radio-labeled drugs)59. (A) Scheme of the treatment, the day of MSCs injection was defined as day 0. A relatively short needle (e.g., 0.5-inch or less) is suggested to help prevent puncture of the intestines or cecum. Intratumoral injection of hydrogel-embedded nanoparticles enhances [3] The study however did not find an increase in conception rate when compared to mating. n=3. 7A). and JavaScript. Epidemiology and natural history of inflammatory bowel diseases. evaluated the therapeutic efficacy of different MSCs sources and delivery routes in experimental emphysema37. Multiple Intravenous Transplantations of Mesenchymal Stem Cells An official website of the United States government. Infiltration (I): 0, no infiltrate; 1, infiltrate around crypt basis; 2, infiltrate reaching to lamina muscularis mucosa layer; 3, extensive infiltration reaching the muscularis mucosa with abundant edema; 4, infiltration of the submucosa layer. In IV group, the colon homing cells were fewer, most of MSCs were trapped in MSCs were rapidly accumulate into the lung and mononuclear phagocytic system. It can significant reduce failure puncture and associated organ damages caused by blind needle puncturing. Adhesions are a leading cause of secondary infertility in women, accounting for 15% to 20% of cases. IHC was performed according to the standard procedures. . In brief, sections were dewaxed and rehydrated by xylol and acohol. Factors such as peritoneal inflammation, surface area, peritoneal blood flow, time of contact, etc, influence the drug transfer. 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. Mice were maintained in a light/temperature-controlled room and allowed to freely access to chow diet and water. Total RNA was extracted with the RNAeasy Plus kit (QIAGEN). In this study, we compared therapeutic efficacy of three MSCs administration routes in DSS-induced colitis. Wang Min, Liang Cong and Hu Hao contributed equally to this work. 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 . The study overall defines appropriate doses and toxicity levels of dl1520 when injected intraperitoneally. 2021. From the overall appearance, the hyperemia and edema of the colon in all MSCs treatment groups became milder than the DSS control. Roddy, G. W. et al. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. After antigen retrieval, the endogenous peroxidase activity was blocked by 1% H2O2 for 10min. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in ADS 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. Br J Rheumatol 36, 390392 (1997). Establishing a xenograft mouse model of peritoneal dissemination of Surg Clin North Am 87, 727741, doi: 10.1016/j.suc.2007.03.004 (2007). After 5 days of DSS contained water, all the subject mice showed strong positive test of fecal occult blood. (B) MSCs signal quantification of five main organs (lung, liver, spleen, kidney and large bowel) and corresponding MLNs. International journal of molecular medicine 37, 115125, doi: 10.3892/ijmm.2015.2413 (2016). Method. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. Inflammatory bowel diseases (IBD) is a broad term that involves chronic inflammation of all or part of the gastrointestinal tract. Intraperitoneal drug therapy: an advantage - PubMed and H.H. In this study, intraperitoneal (IP) injection was used to mimic the human administration route. Proceedings of the National Academy of Sciences of the United States of America 99, 89328937, doi: 10.1073/pnas.132252399 (2002). Intraperitoneal injections are a way to administer therapeutics and drugs through a peritoneal route (body cavity). 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. The increasing evident indicated that cell-cell contact between MSCs and immune cells may also be of importance52,53,54. The supernatants were diluted 1:30 with assay buffer consisting in 50mM phosphate buffer pH 6.0 with 0.167mg/mL o-dianisidine (Sigma) and 0.0005% H2O2.The colorimetric reaction was measured at 450nm between 1 and 3min in a spectrophotometer (Varioskan Flash Multimode Reader, Waltham, MA). The site is secure. Firstly, peritoneal cavity provides an isolated, hemodynamically stable, sterile and nutritious environment with enough growth spaces, which are very critical factors for aggregates forming. B.X. Gastroenterology 132, 944954, doi: 10.1053/j.gastro.2006.12.029 (2007). Injections are given along the midline caudal to the umbilicus or low on the right lateral abdomen. 4F,G). 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. [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. 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). However, human insulin . In IP group, the MSCs existence can be detected at day 1, but gradually decreased with the time, GFP+ cells can be hardly identified in inflamed colon after day 3 (data not shown). PDF EUTHANASIA REFERENCE MANUAL - HumanePro 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. 1C). But for the IP injection, because of more cell accumulation in the inflamed colon, less initial cells might reach minimum effective cell dose. Ex-vivo study was carried out at 1 day post-injection. 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). & Yong, K. Factors that influence short-term homing of human bone marrow-derived mesenchymal stem cells in a xenogeneic animal model. At the end of laparoscopic . 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. 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. 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 DiR dye alone was served as control. Curr Opin Gastroenterol 30, 8496, doi: 10.1097/MOG.0000000000000031 (2014). Acute colitis was induced in C57BL/6 male mice by feeding 5% DSS (molecular weight 40000Da; Sigma) dissolved water for 5 days, followed by five days of regular drinking water according to our previously published study63. Bookshelf & Dennis, J. E. MSCs: Delivery Routes and Engraftment, Cell-Targeting Strategies and Immune Modulation. 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. Intraperitoneal injection is widely used in rodents as a route of drug administration. In this study, the therapeutic efficiency of three different MSCs delivery routes (IP, AI and IV) were compared on DSS-induced colitis mouse model. Yu-Lung Chang, Huei-Yu Lo, Chin-Kan Chan, Xing-hua Pan, Qing-qing Li, Guang-ping Ruan, Hongsheng Yang, Rui Feng, Shenghong Zhang, H. R. Wardill, C. E. M. de Mooij, N. M. A. Blijlevens, Suze A. Jansen, Edward E. S. Nieuwenhuis, Caroline A. Lindemans, Scientific Reports Thus there is a strong impetus to seek more effective approaches for disease management. Distribution of GFP+ MSCs in colon 1 day after injection. Intraperitoneal Versus Interpleural Morphine or Bupivacaine for Pain IP injection showed better amelioration of colitis and may be an ideal delivery way for MSCs in IBD therapy. PubMed Central Cosnes, J., Gower-Rousseau, C., Seksik, P. & Cortot, A. 2020 Apr;17(4):511-522. doi: 10.1080/17425247.2020.1736551. PubMed iQ SYBR Green Supermix and CFX96 (Bio-Rad) were used for template amplification with a primer for each of the transcripts examined. (A) Representative IHC images of each treatment group. Collagen deposition is another indicator for wound healing, however, extensive collagen deposition may hamper the gut reconstitution14. The IV group showed 20.3% ki-67+ cells/crypt. 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. Intraperitoneal Injection - an overview | ScienceDirect Topics The incidence and impact of IBD is increasing worldwide. Article Liu, T. et al. Methods of Euthanasia - Institutional Animal Care and Use Committee PDF Recommended Dose Volumes for Common Laboratory Animals - IQ Consortium (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. The IP technique is an easy technique to master. Human bronchial epithelial cells (BEAS-2B and 16HBE) were purchased from Shanghai Zhongqiao Xinzhou Biological Co., Ltd, and cultured in a complete medium supplemented with growth factors and .1% penicillin-streptomycin. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Since that time, the literatures using stem cells for IBD have expanded. CAS Intraperitoneal injection. Gastroenterology 114, 433440 (1998). Blood 113, 4657, doi: 10.1182/blood-2008-04-154138 (2009). Aliment Pharmacol Ther 32, 939952, doi: 10.1111/j.1365-2036.2010.04439.x (2010). & Dittel, B. N. Isolation of mouse peritoneal cavity cells. Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation and development of colitis-associated cancer. Action at a distance: systemically administered adult stem/progenitor cells (MSCs) reduce inflammatory damage to the cornea without engraftment and primarily by secretion of TNF-alpha stimulated gene/protein 6. Integrative genetic analysis identifies FLVCR1 as a plasma-membrane Brown, S. L. et al. 3; Supplementary Figure S6). A., Ong, J. F. & Karp, J. M. Mesenchymal stem cells: immune evasive, not immune privileged. Article Quantification of collagen fiber was assessed using Image Pro Plus software (version 6.0). Free DiR and healthy mice (without colitis) were served as control. Treatment of dextran sodium sulfate-induced experimental colitis by adoptive transfer of peritoneal cells. Krampera, M. et al. Comparative analysis of paracrine factor expression in human adult mesenchymal stem cells derived from bone marrow, adipose and dermal tissue. However, doubts exist over the use of Fe 3 O 4-nanoparticles in human beings. Generally, the FoxP3 expression was elevated in MSCs treatment (Fig. Use of lipophilic near-infrared dye in whole-body optical imaging of hematopoietic cell homing. 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 . Clinical use of bone marrow, bone marrow concentrate and expanded bone marrow mesenchymal stem cells in cartilage disease. Intramuscular. Histological evaluation was completed in a double-blind fashion by two independent pathologist. Respir Res 15, 118, doi: 10.1186/s12931-014-0118-x (2014). Lipids were . The complications associated with IP injection are major concern. Direct injection of sodium pentobarbital (referred to as euthanasia by . GFP+ cells were detected at the inflamed colon. In the guinea pig, the oral LD 50 value is 10 700 mg kg 1. Because it allows administering a larger volume with more radioactivity, we have investigated this route and the possibility of using it to circumvent the volume constraint we earlier experienced with pretargeting radiotherapy. The transplanted lymphocytes can produce immunoglobulin (Ig), respond to antigens, and survive for months in this chimeric model (hu-PBL SCID). All experimental procedures performed were approved by Animal Welfare and Ethics Committee of the Fourth Military Medical University (FMMU), which are in accordance with the NIH guidelines. PubMed MSCs also showed ability to promote epithelial repair54 and regulate dendritic cells by cell-cell contact mechanism55,56. IBD can be painful and persistent for life, which might decrease the quality of life. The rate and amount of drug transfer in the peritoneum are dependent on several factors. Like pharmacological treatment, the cell dosing might also be an important issue for MSCs therapeutic success21. 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. Then, the bone marrow was flushed out with 1mL syringe. Adv Exp Med Biol 371A, 6165 (1995). Burisch, J. et al. In vivo clearance of free DiR in healthy mice was showed in Supplemental Figure S4. A . Google Scholar. Intraperitoneal injection of magnetic Fe3O4-nanoparticle induces Your peritoneal (payr-ih-toh-NEE-ul) space is the area between the muscles and organs in your abdomen (belly). 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. 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). Vilquin, J. T. & Rosset, P. Mesenchymal stem cells in bone and cartilage repair: current status. Fluorescent intensity was quantified and processed using the Living Image Software (Version 4.2; Caliper Life Science). These immune cells may interact with MSCs and exert regulatory functions to MSCs. Gastroenterology 140, 17851794, doi: 10.1053/j.gastro.2011.01.055 (2011). An example of how intraperitoneal injections can be optimized is depicted in a study where IP injections are used to deliver anesthesia to mice. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/, Wang, M., Liang, C., Hu, H. et al. Once the animal is properly restrained (as described above for SC injections) the injection site is . 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. These findings could be advanced by studying how the route of injection affects the organs in the peritoneal cavity. Mice are usu The data showed that the TSG-6 levels increased with time in both IP and IV injection groups, while in DSS control group, the TSG-6 level decreased from 48h to 72h. Although there is no significant difference among three injection groups at 48h after MSCs transplantation, the serum TSG-6 was significant higher in IP injection group compared with naive group (P=0.024). CAS M.W., C.L. Intraperitoneal Drug Administration - an overview | ScienceDirect Topics It is more often applied to animals than to humans. Near-infrared imaging and quantification of MSCs transplants. Intraperitoneal Injection Is Not a Suitable Administration Route for In humans, numerous plasma molecules prevent or modulate cell stimulation by microbial products, either by neutralizing the agonists (eg, bactericidal permeabilityincreasing protein, . 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. Therapeutic strategies should be based on a sound and thorough understanding of the disease mechanisms, if possible, however the causes of IBD are still unclear6. Karp, J. M. & Leng Teo, G. S. Mesenchymal stem cell homing: the devil is in the details. doi: 10.1002/14651858.CD005284.pub3. [citation needed]. However, if proper placement of the needle occurs, this is not necessary. The results of this IP injection were the disappearance of the ascites associated with the rupture. 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. A protocol for isolation and culture of mesenchymal stem cells from mouse compact bone. ADS This shows an important limitation to the use of IP therapy. The number of therapeutic cells that can migrate and colonize at the injury site is a decisive prerequisite for the success of cytotherapy. was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity . Complications associated with intraperitoneal chemotherapy catheters. 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. 2021 Jul 23;2021:2303417. doi: 10.1155/2021/2303417. 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. Stem cell research & therapy 6, 55, doi: 10.1186/s13287-015-0066-5 (2015). Our findings suggested that IP delivery showed higher MSCs and better experimental colitis recovery, might be an ideal way for MSCs therapy in IBD. PubMed Central 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. Journal of biomedical science 15, 585594, doi: 10.1007/s11373-008-9256-9 (2008). 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. PubMed The primer sequences used were listed in Supplementary Table S1. Supplies: Best way for mesenchymal stem cells transplantation for colitis. Intra-abdominal adhesions can be a considerable source of morbidity and mortality. Mouse insulin gradually decreased and was no more detectable 13 weeks after STZ injection. Endoscopic fluorescence imaging experiments were performed at 1-h postinjection of FA-NPs, celecoxib/FA-NPs or FNC-NPs using a Karl Storz-Endoskope System. Interaperitoneal Administration of lpha-Tocopherol Loaded Nanoparticles Improves Ischemia-Reperfusion Injury in Rat Ovaries Torsion and Detorsion Model.
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