Negative impact of bone-marrow-derived mesenchymal stem cells on dextran sulfate sodium-induced colitis

Abstract

AIM:To investigate the effects of mesenchymal stem cells (MSCs) on dextran sulfate sodium-induced inflammatory bowel disease (IBD).METHODS: C57BL/6 mice were fed 3.5% (g/L) dextran sulfate sodium. On day seven, the mice received intraperitoneal injections of 1 × 10 6 MSCs. The survival rate, disease activity index values, and body weight, were monitored daily. On day ten, colon lengths and histopathologic changes were assessed. In addition, immunoregulatory changes following MSC administration were evaluated by determining the levels of effector T cell responses in the spleen and mesenteric lymph nodes, and the expression levels of inflammatory cytokines in homogenized colons. RESULTS:Intraperitoneal administration of MSCs did not prevent development of colitis and did not reduce the clinicopathologic severity of IBD. No significant difference was evident in either survival rate or disease activity index score between the control and MSCtreated group. Day ten-sacrificed mice exhibited no significant difference in either colon length or histopathologic findings. Indeed, the MSC-treated group exhibited elevated levels of interleukin (IL)-6 and transforming growth factor-β, and a reduced level of IL-10, in spleens, mesenteric lymph nodes, and homogenized colons. The IL-17 level was lower in the mesenteric lymph nodes of the MSC-treated group (P = 0.0126). In homogenized colons, the IL-17 and tumor necrosis factor-α (P = 0.0092) expression levels were also lower in the treated group. CONCLUSION: MSC infusion provided no significant

New Strategies for Overcoming Limitations of Mesenchymal Stem Cell-Based Immune Modulation

“…In pre-clinical studies, MSCs were hypothesized to exert immunomodulatory effects that would improve the pathogenesis of IBD. Previously, we reported for the first time that MSCs are not clinically beneficial in IBD treatment ( 72 ). Other pre-clinical studies have suggested the positive outcomes of MSCs for the treatment of IBD; however, in these studies, MSCs were not used alone, but rather genetically modified to IL-12p40 ( 73 ), coated with antibodies ( 74 ), or genetically depleted with autoimmune regulators ( 75 ).…”

Comparative Study on In Vitro Culture of Mouse Bone Marrow Mesenchymal Stem Cells

“…A key factor often ignored by researchers is that the physiological oxygen concentration in the bone marrow varies from 1% to 7%. Although low-oxygen culture conditions have been recognized to exert an important impact on BM-MSCs, mouse BM-MSCs are cultured in 21% oxygen condition in many studies [ 2 , 7 , 8 , 17 , 30 – 32 ]. Here, we compared cell proliferation, clonogenicity, and surface markers between 21%, 10%, and 5% oxygen conditions.…”

Safety and therapeutic effect of mesenchymal stem cell infusion on moderate to severe ulcerative colitis

“…In a study by Forte et al (40), human umbilical cord MSCs were used to treat acute trinitrobenzene sulfonic acid-induced UC. In another study, the inflammatory markers such as IL-17, IL-23, IFN-γ and IL-6 were measured to assess the therapeutic efficacy of human umbilical cord MSCs and were shown to be significantly decreased in the treated mice (41). In the present study, during the follow-up, the levels of cytokines in group I, including TNF-α, IL-6 and IFN-γ, were not significantly changed compared with group II.…”