Scientific Reports (Sci Rep) Shamsi M, Sedaghatkish A, Dejam M, Saghafian M, Mohammadi M, Sanati-Nezhad A. A modified human recombinant type 5 adenovirus . Google Scholar. MSCs have been well characterized regarding their ability to produce a range of cell cytokines, which have a profound effect on modulating the immune system. Arthritis and rheumatism 56, 11751186, doi: 10.1002/art.22511 (2007). 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. Stem cell transplantation: the lung barrier. Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5(+) stem cell. We also evaluated serum TSG-6 in three MSCs administration route. If injecting a hazardous substance (biohazard, radiation hazard or chemical hazard), include precautions in the Animal Care Protocol for human safety (e.g. 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. A relatively short needle (e.g., 0.5-inch or less) is suggested to help prevent puncture of the intestines or cecum. 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 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. Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Yuanmingyuan West Road No. PubMed Intraosseous. Intraperitoneal (IP) route of drug administration in laboratory animals is a common practice in many in vivo studies of disease models. The few examples that do exist pertain to the treatment of pancreatic/ovarian cancers and injections of other drugs in clinical trials. However, one recent published paper showed inconsistent results with ours, in which IV injection was identified better in comparison with intraperitoneal injection31. 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. With the computer-assisted software, we calculated the density of collagen fibers (%) of all groups. Intraperitoneal (IP) Injection (Injection of Sodium Pentobarbital . Journal of biomedical science 15, 585594, doi: 10.1007/s11373-008-9256-9 (2008). It is more often applied to animals than to humans. Blood 118, 330338, doi: 10.1182/blood-2010-12-327353 (2011). 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). There are a variety of uses and possibilities for many more in the future with further research and approval. During the observation, the body weight changes and fecal blood and their survival date was faithfully record. Article 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. Levy, O. et al. In addition, even MSCs could formed aggregates in those harsh conditions, there still be a highly risk of self-removal. 2010 May;27(5):735-8. doi: 10.1007/s11095-009-0031-z. . A disadvantage of using intraperitoneal injections is that they can have a large variability in effectiveness and misinjection. From whole-body disease recovery, the amount of MSCs colons engraftment, tissue histological evaluation as well as levels of cytokines and TSG-6. Adhesions are a leading cause of secondary infertility in women, accounting for 15% to 20% of cases. For example, if using a dose of 1 U kg -1 , a concentration of 0.2 U ml -1 is suitable. Comparison of colonic inflammatory cytokine TNF- and IL-10 at day 3. Li, Y. P. et al. Neutrophil infiltration was monitored by measuring MPO activity67. It was concluded that the intraperitoneal injection had the highest survival rate of 87.5%. PubMed It is more often applied to animals than to humans. Cell and tissue research 347, 419427, doi: 10.1007/s00441-011-1306-3 (2012). Br J Rheumatol 36, 390392 (1997). . 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. 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. Article prepared Figure 5. and transmitted securely. Mouse insulin gradually decreased and was no more detectable 13 weeks after STZ injection. (A) MSCs were labeled with DiR dye and given by three different ways. CAS Journal of biomedical optics 11, 050507, doi: 10.1117/1.2364903 (2006). mRNA-engineered mesenchymal stem cells for targeted delivery of interleukin-10 to sites of inflammation. Collagen deposition is another indicator for wound healing, however, extensive collagen deposition may hamper the gut reconstitution14. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. Rodents. and S.J. 2020 Apr;17(4):511-522. doi: 10.1080/17425247.2020.1736551. In the guinea pig, the oral LD 50 value is 10 700 mg kg 1. Generally, the FoxP3 expression was elevated in MSCs treatment (Fig. The results of this IP injection were the disappearance of the ascites associated with the rupture. Stem Cell Res Ther 3, 51, doi: 10.1186/scrt142 (2012). Meanwhile, GFP+ MSCs (collected from transgenic mice) were used to determine MSCs specific location. It was concluded that there is evidence that IP may not be the best method of euthenasia due to possibilities of missinjection. Gut 63, 588597, doi: 10.1136/gutjnl-2013-304636 (2014). Article Vilquin, J. T. & Rosset, P. Mesenchymal stem cells in bone and cartilage repair: current status. Wang Min, Liang Cong and Hu Hao contributed equally to this work. Before The IP and AI groups showed mean 50.4% and 46.7% Ki-67+ cells/crypt respectively. 2B). Toll-like receptors 3 and 4 are expressed by human bone marrow-derived mesenchymal stem cells and can inhibit their T-cell modulatory activity by impairing Notch signaling. 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). To determined cytokine in colon mucosa, protein extracts were isolated by homogenization of colonic segments (50mg tissue/mL) in 50mmol/L Tris-HCl, pH 7.4, with 0.5mmol/L dithiothreitol and 10 g/mL of a cocktail of proteinase inhibitors (Sigma). the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in A., Ong, J. F. & Karp, J. M. Mesenchymal stem cells: immune evasive, not immune privileged. designed the research. Dou, S., Smith, M., Wang, Y., Rusckowski, M. & Liu, G. Intraperitoneal injection is not always a suitable alternative to intravenous injection for radiotherapy. 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. 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 The labeled cells were twice with warm fresh medium at 1500rpm for 5min to ensure complete removal of any unbound dye. 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. This case is a good example of how IP injections can be used to deliver a drug that can help to treat or cure a medical diagnosis over the use of other routes of delivery. From the overall appearance, the hyperemia and edema of the colon in all MSCs treatment groups became milder than the DSS control. Some of the examples depict situations where IP injections are not ideal, while others prove the advantageous uses if this delivery method. Injected dissociative agent combinations. Treatment of dextran sodium sulfate-induced experimental colitis by adoptive transfer of peritoneal cells. Best way for mesenchymal stem cells transplantation for colitis. 4 The scalp was disinfected and a midline incision was made in the skin. seem to have found the key drug of MSCs in the treatment of colitis, TSG-647. There is a little fluid in between the peritoneal lining and your organs. Burisch, J. et al. Intraperitoneally applied drug forms are supposed to be located in the peritoneal 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. The GFP+ MSCs were found at inflamed colon in both IP and AI groups 24h after MSCs injection. Figure 1. The increasing evident indicated that cell-cell contact between MSCs and immune cells may also be of importance52,53,54. Language links are at the top of the page across from the title. 2021 Jul 23;2021:2303417. doi: 10.1155/2021/2303417. Google Scholar. Human peripheral blood lymphocytes (hu-PBL) can be adoptively transferred by intraperitoneal injection into mice with severe combined immunodeficiency (SCID). CBSKL2015Z01 and CBSKL2015Z12), PLA 12th Five-Year Program (BSW11J013) and National Science and Technology Major Project (No. Gastroenterology 132, 944954, doi: 10.1053/j.gastro.2006.12.029 (2007). Pull back on the plunger to ensure negative pressure prior to injecting. & Ramesh, T. Comparative investigation of the differentiation capability of bone-marrow- and adipose-derived mesenchymal stem cells by qualitative and quantitative analysis. [2] Intraperitoneal injections can be similar to oral administration in that hepatic metabolism could occur in both. Mol Ther 18, 13651372, doi: 10.1038/mt.2010.54 (2010). injections. After antigen retrieval, the endogenous peroxidase activity was blocked by 1% H2O2 for 10min. Would you like email updates of new search results? In this study, intraperitoneal (IP) injection was used to mimic the human administration route. Qualitatively, the existence of non-portal drainage was demonstrated by . n=3 per group. Review article: stem cell therapies for inflammatory bowel disease - efficacy and safety. Get the most important science stories of the day, free in your inbox. Hommes, D., Colombel, J. F., Emery, P., Greco, M. & Sandborn, W. J. MeSH Horses and other large animals: 1 mL per 10 lb of body weight, to a maximum . The medium was refreshed every 23 days and third- and fourth-passage cells were used for all experiments. 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 . Federal law restricts this drug to use by or on the order of a licensed veterinarian. There are few accounts of the use of intraperitoneal injections prior to 1970. Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population. gynecological and gastrointestinal cancers and has shown very promising results. Kenny et al. Thank you for visiting nature.com. Comparative analysis of paracrine factor expression in human adult mesenchymal stem cells derived from bone marrow, adipose and dermal tissue. Currently, two types of stem are used for the treatment of IBD, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Sci Rep 5, 16760, doi: 10.1038/srep16760 (2015). Cancer cell 23, 107120, doi: 10.1016/j.ccr.2012.11.013 (2013). Once the animal is properly restrained (as described above for SC injections) the injection site is . By submitting a comment you agree to abide by our Terms and Community Guidelines. 3) and the IV group preserved fewer cell number. 6A). and K.W. 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). [5] In 1967, the production of amnesia was studied through an injection of physostigmine. Article Atreya, R. & Neurath, M. F. Chemokines in inflammatory bowel diseases. This led to the patients being able to be discharged earlier than when anesthesia was administered continuously. Thus there is a strong impetus to seek more effective approaches for disease management. Some research showed exogenous CD34 stem cells migration towards the inflamed colon and differentiation into endothelial cells40. In addition, IP showed more intense Ki-67 stain in bottom of the crypt, which suggested more active mucosa repair proliferation (Fig. 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. Lee et al. However, they found the migrated PCs was very few and these may attribute to: 1) the recipient are heathy rat. But this study at least pointed out the possible migration route for cells by intraperitoneal injection. In the meantime, to ensure continued support, we are displaying the site without styles This site needs JavaScript to work properly. The overall therapeutic factors, MSCs migration and targeting as well as local immunomodulatory cytokines and FoxP3+ cells infiltration were analyzed. official website and that any information you provide is encrypted [8], A good example of how intraperitoneal injections work is depicted through "The distribution of salicylate in mouse tissues after intraperitoneal injection" because it includes information on how a drug can travel to the blood, liver, brain, kidney, heart, spleen, diaphragm, and skeletal muscle once it has been injected intraperitoneally.[9]. Influence of Systemic Administration of Coq10 Nanoparticles on Ischemia-Reperfusion Injury on Ovaries in Rat. However, whether the lymphocytes actually . Generally, the mice were killed by cervical dislocation. In consistence with PCR results, IP groups showed higher IL-10 and lower TNF- than other MSCs delivery ways (Fig. They found that PCs can directly migrated from peritoneal cavity and some of them were found at intestinal villi. Google Scholar. Gao, J., Dennis, J. E., Muzic, R. F., Lundberg, M. & Caplan, A. I. However, for IV injection, we and others found most mice will lead increased mortality because of potential pulmonary cell embolus when the cell dose increase to 110722. Injections Intraperitoneal (IP) "Mouse" Once animal is restrained turn over so abdomen is exposed. (D) Semi-quantitative fecal occult blood test on day 3. The first major problem with IV route is the pulmonary first-pass effects, which cause significant entrapment of cells15. some potent chemo and radio-labeled drugs)59. L.Z. . However, no significant TSG-6 difference was found between AI and IV groups. [citation needed], In humans, the method is widely used to administer chemotherapy drugs to treat some cancers, particularly ovarian cancer. X.W., Y.H., Y.N. 81421003 and No. Another study by coating MSCs with VCAM-1 also exhibited an increased MSCs migration to the inflamed colon and promoted tissue repair capacity25. study on peritoneal cells (PCs) migration to gut may give us some hints27. 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).