Systemic Infusion of Bone Marrow-Derived Mesenchymal Stem Cells for Treatment of Experimental Colitis in Mice

He, Xiaowen; He, Xiaosheng; Lian, Lei; Wu, Xiaojian; Lan, Ping

doi:10.1007/s10620-012-2290-5

Cited by 76 publications

(80 citation statements)

References 33 publications

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“…Other authors did use MSCs alone to treat IBD. However, although one report claimed that multiple MSC infusion improved the clinical symptoms of IBD, the levels of only TNF-α and IL-1β were shown [10] . Some clinical studies have explored the effects of adipose-derived stem cells (ASCs) and MSCs in IBD patients (Table 2).…”

Section: Discussionmentioning

confidence: 97%

“…However, some authors did not use MSCs alone, rather subjecting the MSCs to IL-12p40 transduction [11] , autoimmune regulator knockout [10] , or coating with antibodies against MAdCAM-1 and VCAM-1 [9] . Other authors did use MSCs alone to treat IBD.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the utility of mesenchymal stem cells (MSCs) has been suggested, because MSCs exert immunosuppressive effects and aid in tissue repair [3][4][5][6][7][8] . Some preclinical studies explored the utility of MSCs in treatment of IBD [9][10][11][12] . MSCs were injected subcutaneously, intravenously, or intraperitoneally, and attenuated IBD.…”

Section: Introductionmentioning

confidence: 99%

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

Nam¹,

Kim²,

Im³

et al. 2015

WJG

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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

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Nam¹,

Kim²,

Im³

et al. 2015

WJG

View full text Add to dashboard Cite

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“…Despite the success of this method in fistulising CD, alternative administration routes that facilitate homing to multiple inflammatory sites may be required to treat pathological manifestations of IBD in its entirety. Systemic administration of MSCs was used in clinical trials treating luminal CD 32,33) and is predominant in studies of experimental colitis ( 34,35) however other studies have not observed this phenomenon [36][37][38] . Additionally, it is likely that MSCs can become sequestered in other various tissues connected to the circulatory system when systemically injected 39) .…”

Section: Route Of Msc Administrationmentioning

confidence: 99%

Mesenchymal stem cells for the treatment of inflammatory bowel disease: from experimental models to clinical application

Stavely

Sakkal

Stojanovska

et al. 2014

Inflammation and Regeneration

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AustraliaInflammatory Bowel Disease (IBD) is a highly debilitating and potentially fatal idiopathic disorder of the intestinal tract which is exceedingly prevalent in westernized society; however there is concern of an IBD epidemic in Asia due to increasing incidence rates. There is no cure for IBD with current treatments limited by their inefficacy, toxicity and adverse side-effects; thus necessitating the search for novel therapies. In the past decade mesenchymal stem cells (MSCs) have become attractive candidates for the cellular based therapy of IBD. MSCs are easily isolated and expanded from adult bone-marrow and adipose tissue; they possess unique therapeutic characteristics including the ability to home to sites of tissue damage and inflammation, facilitate tissue repair and modulate the immune system. The administration of MSCs in animal models of experimental colitis and clinical trials of fistulising and luminal Crohn's disease have yielded promising results, however an unequivocal therapeutic mechanism remains elusive. This review will explore the clinical application of MSCs in IBD and current evidence from experimental models of colitis elucidating their potential to ameliorate intestinal inflammation.Rec .The cause of IBD is unknown but concordant twin studies have revealed that the development of IBD is likely to require a multi-genetic predisposition and an environmental . The clinical application of MSCs in CD and evidence for the possible mechanisms elucidating their potential to regenerate intestinal epithelium and reduce inflammation in experimental models of colitis will be reviewed. Efficacy of MSCs in Clinical TrialsClinical trials using MSCs for the treatment of CD fistulae and luminal inflammation have demonstrated that MSC therapy in IBD is both efficacious and feasible (summarised in . Furthermore, sustained closure of fistulae has been achieved in 88-100% of subjects 8-12 months after a course of MSC therapy 26,28) ; however these effects are relatively transient given that only 58% of subjects maintain closure after 3 years 29) . This suggests that repeated treatment may be required to maintain the therapeutic benefits of MSC therapy.While autologous and allogeneic AT-MSCs have both demonstrated efficacy in the healing of fistulae, further evidence is required to determine long-term immune tolerance in patients with repeated allogeneic MSC exposure.Bacterial contamination has posed a problem in the expansion of autologous MSCs in the past causing delay in treatment 24,30) . If allogeneic MSCs are determined to be equally efficacious, pre-prepared sources for treatment could prevent such setbacks.One clinical trial has determined that MSCs were as effective in treating fistulae of cryptoglandular origin as they were for fistulae resultant of CD 32,33) . In a study

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“…Ha habido algunos estudios donde se utilizaban ratones con enfermedad inflamatoria intestinal inducida que han sido tratados con MSCs, demostrando la viabilidad de esta aplicación (19) (20). En otro artículo, se expone el caso de cuatro pacientes con colitis ulcerosa y leucemia que tras ser tratados con ASCT permanecieron en remisión de ambas patologías (21).…”

Section: Colitis Ulcerosaunclassified

Stem cell treatment in gastroenterology and hepatology

Guirado¹,

Arco²

2014

Actual. Med.

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Tratamiento con células madre en gastroenterología y hepatología ResumenLas células madre están presentes en la mayoría de los tejidos del organismo, permitiendo su renovación perió-dica y su regeneración en caso de producirse un daño tisular. Debido a su capacidad de autorrenovación y de diferenciación en diversos tipos celulares maduros, se están estudiando para el tratamiento de diferentes enfermedades del aparato digestivo, como la enfermedad inflamatoria intestinal, la celiaquía y en el fallo hepático. En esta revisión se incluyen resultados sobre el beneficio de su posible aplicación terapéutica en el campo de la gastroenterología y hepatología, a pesar de que se necesitan muchos más estudios para la comprensión de la biología de las células madre y de su discutida relación con el proceso de carcinogénesis. AbstractStem cells are present in the most human tissues. They have the capabilities of self-renewal and differentiation, allowing the regeneration of a tissue in case of damage. Due to those properties, stem cells have been studied as treatment of numerous gastrointestinal and liver diseases, i.e., inflammatory bowel disease, celiac disease and liver failure. In this review we present results of therapeutic applications of stem cells in fields of gastroenterology and hepatology, even though further studies are needed to better understand biology of stem cells and their controversial role in the carcinogenesis process.

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Systemic Infusion of Bone Marrow-Derived Mesenchymal Stem Cells for Treatment of Experimental Colitis in Mice

Abstract: Systemic infusion of bone marrow-derived MSCs may exert therapeutic efficacy on acute DSS-induced colitis in mice through their anti-inflammatory effects, which demonstrates the feasibility of using bone marrow-derived MSCs to treat IBD.

Cited by 76 publications

References 33 publications

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

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

Mesenchymal stem cells for the treatment of inflammatory bowel disease: from experimental models to clinical application

Stem cell treatment in gastroenterology and hepatology

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