Intravenous<i>vs</i>intraperitoneal mesenchymal stem cells administration: What is the best route for treating experimental colitis?

Gonçalves, Fabiany da Costa; Schneider, Natália; Pinto, Flávia Santos Twardowski; Meyer, Fabíola Schons; Visioli, Fernanda; Pfaffenseller, Bianca; Lopez, Patrícia Luciana da Costa; Passos, Eduardo Pandolfi; Cirne-Lima, Elizabeth Obino; Meurer, Luíse; Paz, Ana Helena da Rosa

doi:10.3748/wjg.v20.i48.18228

Cited by 65 publications

(52 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…IBD exhibit chronic inflammation with enhanced IFN-γ production in intestinal lamina propria, which is followed by an excess of TNF-α and neutrophil infiltration in CD [9,[40][41][42][43][44][45], in contrast to the excess of IL-4, IL-5 and IL-13 in UC [9,40,42]. The experimental model of TNBS enema is immunologically similar to CD in humans [37].…”

Section: Discussionmentioning

confidence: 99%

A single administration of human adipose tissue-derived mesenchymal stromal cells (MSC) induces durable and sustained long-term regulation of inflammatory response in experimental colitis

Alves

Sousa

Fonseca

et al. 2019

Clinical &Amp; Experimental Immunology

View full text Add to dashboard Cite

Current therapies for inflammatory bowel diseases (IBD) are aimed at controlling the exacerbated response in the gut, but no treatment is fully effective for many refractory patients. Mesenchymal stromal cells (MSC) are multi-potent cells with regulatory immunosuppressive activity that may control inflammatory diseases. In this study, we investigated the short-and especially the long-term protective effects of MSC on experimental colitis. We show that MSC elicited protection to acute intestinal inflammation with gain of weight, improvement in the clinical disease score and expressive reduction in the mortality rate of treated mice. MSC changed the population of neutrophils, eosinophils and augmented the frequency of CD4 T lymphocytes in the gut-draining lymph nodes, together with reduced accumulation of these cells in the colon intraepithelial compartment. Interestingly, there were increased levels of programmed death 1 (PD-1) and glucocorticoid-induced tumour necrosis factor receptor family-related receptor (GITR) in the spleen regulatory T cells of mice that received MSC treatment, which also presented a reversal in the pattern of immune response in the gut, with diminished inflammatory, T helper type 1 (Th1) and Th17 profile, in contrast to augmented Th2 responses. Most strikingly, this balanced response elicited by a single administration of MSC during the acute colitis persisted long-term, with restored goblet cells, eosinophils and maintenance of elevated gut interleukin (IL)-4, besides increased CD4 + CD25 + PD-1 + cells in the spleen and reduced Th17 response in mesenteric lymph nodes (MLN) of treated mice on day 60. Taken together, our findings provided a significant contribution to translational immunology by pointing human adipose tissue-derived MSC as a novel therapeutic approach with long-term beneficial regulatory effects in experimental colitis.

show abstract

Section: Discussionmentioning

confidence: 99%

A single administration of human adipose tissue-derived mesenchymal stromal cells (MSC) induces durable and sustained long-term regulation of inflammatory response in experimental colitis

Alves

Sousa

Fonseca

et al. 2019

Clinical &Amp; Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…A meta‐analysis of 477 patients demonstrated a significant improvement in healing rate and reduction in recurrence for patients treated with ASC relative to other treatments . These improvements in clinical outcomes were likely secondary to the effects of ASCs to reduce inflammation through reduction of proinflammatory cytokines, induction of anti‐inflammatory cytokines, increase in T regulatory cell populations, and conversion of macrophages to a regulatory phenotype .…”

Section: Resultsmentioning

confidence: 99%

“…The Food and Drug Administration regulates the use of stem cell‐based products in the United States according to the Public Health Safety Act . This act states that stem cells are subject to regulation if they are processed, used for purposes that are not their normal function, also known as “nonhomologous use,” combined with non‐tissue materials, or used for metabolic purposes . However, some investigators claim that the use of stem cells for treatment of disease is not under the purview of the FDA as these stem cells are administered as part of medical procedures .…”

Section: Discussionmentioning

confidence: 99%

Concise Review: Using Fat to Fight Disease: A Systematic Review of Nonhomologous Adipose-Derived Stromal/Stem Cell Therapies

et al. 2018

View full text Add to dashboard Cite

The objective of this Review is to describe the safety and efficacy of adipose stem/stromal cells (ASC) and stromal vascular fraction (SVF) in treating common diseases and the next steps in research that must occur prior to clinical use. Pubmed, Ovid Medline, Embase, Web of Science, and the Cochrane Library were searched for articles about use of SVF or ASC for disease therapy published between 2012 and 2017. One meta-analysis, 2 randomized controlled trials, and 16 case series were included, representing 844 human patients. Sixty-nine studies were performed in preclinical models of disease. ASCs improved symptoms, fistula healing, remission, and recurrence rates in severe cases of inflammatory bowel disease. In osteoarthritis, ASC and SVF improved symptom-related, functional, radiographic, and histological scores. ASC and SVF were also shown to improve clinical outcomes in ischemic stroke, multiple sclerosis, myocardial ischemia, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, chronic liver failure, glioblastoma, acute kidney injury, and chronic skin wounds. These effects were primarily paracrine in nature and mediated through reduction of inflammation and promotion of tissue repair. In the majority of human studies, autologous ASC and SVF from liposuction procedures were used, minimizing the risk to recipients. Very few serious, treatment-related adverse events were reported. The main adverse event was postprocedural pain. SVF and ASC are promising therapies for a variety of human diseases, particularly for patients with severe cases refractory to current medical treatments. Further randomized controlled trials must be performed to elaborate potential safety and efficacy prior to clinical use. Stem Cells 2018;36:1311-1328.

show abstract

“…1) Anal injections are usually used to study large intestinal diseases [49]. 2) The intravenous injection is historically the most common method for MSC delivery [15, 17, 23, 24, 47, 48, 50] and was identified to be better in comparison with intraperitoneal injection [51]. 3) Large volumes of ascites fluid accumulate in the peritoneal cavity in ANP.…”

Section: Discussionmentioning

confidence: 99%

Effect of mesenchymal stem cells on small intestinal injury in a rat model of acute necrotizing pancreatitis

et al. 2017

View full text Add to dashboard Cite

BackgroundAcute necrotizing pancreatitis (ANP) is often complicated by multiple organ failure. The small intestine is frequently damaged during ANP. Capillary leakage in multiple organs during ANP is one of the most important causes of multiple organ dysfunction. Damage to the capillary endothelial barrier and impaired water transportation could lead to capillary leakage in ANP.MethodsSprague–Dawley (SD) rats were randomized into a control group, the ANP group, the culture media-treated group, or the bone marrow-derived mesenchymal stem cell (BMSC)-treated group (30 rats in each group). Ten rats in each group were sacrificed at 6, 12, and 24 h after induction of experimental models. Serum, ascites, pancreatic, and small intestinal samples were collected. The levels of serum and ascites albumin and amylases were measured, pancreatic histology was assessed, and the connection changes between vessel endothelial cells were evaluated using scanning electron microscopy (SEM). Capillary leakage in small intestinal tissue was observed visually by tracking fluorescein isothiocyanate (FITC)-albumin, and was measured by the Evans blue extravasation method. The location and expression of aquaporin 1 (AQP1) in the small intestine was analyzed using immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blot.ResultsThe outcomes showed that the level of serum and ascites amylase is elevated. Conversely, the level of serum albumin is decreased while ascites albumin is elevated. There is damage to pancreatic tissue, and the small intestinal capillary endothelial barrier was aggravated. Furthermore, the expression of AQP1 was reduced significantly after induced ANP. Following treatment with MSCs, the elevation of amylase and the decrease of serum albumin were inhibited, the damage to pancreatic tissue and the level of small intestinal capillary leakage was alleviated, and the downregulation of AQP1 was reversed.ConclusionsIn conclusion, MSC therapy could alleviate small intestinal injury in rats with ANP, the mechanism of which might be related to reduction of damage to the small intestinal capillary endothelial barrier, and increased expression of AQP1 in the small intestine.

show abstract

Intravenousvsintraperitoneal mesenchymal stem cells administration: What is the best route for treating experimental colitis?

Abstract: Our results demonstrate that intravenous treatment is a superior method for reducing colon inflammation compared with intraperitoneal therapy.

Cited by 65 publications

References 39 publications

A single administration of human adipose tissue-derived mesenchymal stromal cells (MSC) induces durable and sustained long-term regulation of inflammatory response in experimental colitis

A single administration of human adipose tissue-derived mesenchymal stromal cells (MSC) induces durable and sustained long-term regulation of inflammatory response in experimental colitis

Concise Review: Using Fat to Fight Disease: A Systematic Review of Nonhomologous Adipose-Derived Stromal/Stem Cell Therapies

Effect of mesenchymal stem cells on small intestinal injury in a rat model of acute necrotizing pancreatitis

Contact Info

Product

Resources

About