Improving the Efficacy of Mesenchymal Stem/Stromal-Based Therapy for Treatment of Inflammatory Bowel Diseases

López‐Santalla, Mercedes; Garín, Marina I.

doi:10.3390/biomedicines9111507

Cited by 15 publications

(10 citation statements)

References 137 publications

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“…As it shares many features with human CD, the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis animal model has been used to study the mechanism and treatment of human CD. Preclinical animal experiments have confirmed that MSCs could significantly improve clinical abnormalities in TNBS-induced colitis mice and reduce lesion scores and inflammation in the gut [ 13 ]. However, the mechanism by which MSCs alleviate CD is still unclear and it needs further elucidation.…”

Section: Introductionmentioning

confidence: 99%

Human umbilical cord-derived mesenchymal stem cells ameliorate experimental colitis by normalizing the gut microbiota

Yang

Liu

et al. 2022

Stem Cell Res Ther

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Background Crohn's disease (CD) is a chronic non-specific inflammatory bowel disease. Current CD therapeutics cannot fundamentally change the natural course of CD. Therefore, it is of great significance to find new treatment strategies for CD. Preclinical and clinical studies have shown that mesenchymal stromal cells (MSCs) are a promising therapeutic approach. However, the mechanism by which MSCs alleviate CD and how MSCs affect gut microbes are still unclear and need further elucidation. Methods We used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in mice and analysed the microbiota in faecal samples from the control group, the TNBS group and the TNBS + MSC group with faecal 16S rDNA sequencing. Subsequent analyses of alpha and beta diversity were all performed based on the rarified data. PICRUStII analysis was performed on the 16S rRNA gene sequences to infer the gut microbiome functions. Results MSC Treatment improved TNBS-induced colitis by increasing survival rates and relieving symptoms. A distinct bacterial signature was found in the TNBS group that differed from the TNBS + MSC group and controls. MSCs prevented gut microbiota dysbiosis, including increasing α-diversity and the amount of Bacteroidetes Firmicutes and Tenericutes at the phylum level and decreasing the amount of Proteobacteria at the phylum level. MSCs alleviated the increased activities of sulphur and riboflavin metabolism. Meanwhile some metabolic pathways such as biosynthesis of amino acids lysine biosynthesis sphingolipid metabolism and secondary bile acid biosynthesis were decreased in the TNBS group compared with the control group and the TNBS + MSC group Conclusions Overall, our findings preliminarily confirmed that colitis in mice is closely related to microbial and metabolic dysbiosis. MSC treatment could modulate the dysregulated metabolism pathways in mice with colitis, restoring the abnormal microbiota function to that of the normal control group. This study provides insight into specific intestinal microbiota and metabolism pathways linked with MSC treatment, suggesting a new approach to the treatment of CD.

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Section: Introductionmentioning

confidence: 99%

Human umbilical cord-derived mesenchymal stem cells ameliorate experimental colitis by normalizing the gut microbiota

Yang

Liu

et al. 2022

Stem Cell Res Ther

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“…Based on numerous studies in experimental immunemediated disorders, better efficacy is achieved when the MSCs were infused during the early phases of the disease (9,33). We therefore infused 3x10 6 MSCs per mouse during the onset of joint inflammation soon after serum administration from K/ BxN arthritic mice.…”

Section: Discussionmentioning

confidence: 99%

Assessment of mesenchymal stem/stromal cell-based therapy in K/BxN serum transfer-induced arthritis

et al. 2022

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and cartilage/bone destruction with systemic comorbidities. Despite advances in understanding the aetiology of RA and novel biologic drugs, a substantial number of individuals with RA remain intolerant or resistant to these therapies. In this context, mesenchymal stem/stromal cell (MSC)-based therapy has emerged as an innovative therapeutic alternative to address unresolved treatment issues for patients with RA thanks to the immunomodulatory properties of these cells. The majority of preclinical studies in MSC-based therapy have been conducted using the well-known collagen-induced arthritis (CIA) mouse model however due to its low incidence, the mouse strain restriction and the prolonged induction phase of collagen-induced arthritis, alternative experimental models of RA have been developed such as K/BxN serum transfer-induced arthritis (STIA), which mimics many of human RA features. In this study, we evaluate whether the K/BxN STIA model could be used as an alternative model to study the immunomodulatory potential of MSC-based therapy. Unexpectedly, our data suggest that adipose-derived MSC-based therapy is unsuitable for modulating the progression of K/BxN serum-transfer arthritis in mice despite the various experimental parameters tested. Based on the differences in the immune status and monocytic/macrophage balance among the different arthritic models, these results could help to identify the cellular targets of the MSCs and, most importantly to predict the RA patients that will respond positively to MSC-based therapy.

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“…In addition to the low survival rates of stem cells that are injected intravenously into the targeted area to treat intracranial diseases, the injected stem cells may also migrate to other sites and produce side effects. Therefore, some techniques have been developed to promote colonic mucosal healing through interventional radiology and an intra-arterial injection of MSCs into the ileum, and clinical trials have also suggested their safety and efficacy[ 32 ]. In a recent study, a temperature-responsive Petri dish was used to endoscopically transplant MSC sheets into the inflammatory area of mice with TNBS-induced colitis.…”

Section: Use Of Mscs and Their Derivatives In The Treatment Of Ibdmentioning

confidence: 99%

“…Currently, patients with IBD are treated with 5-ASA compounds (mainly mesalamine), glucocorticoids (conventional and other forms, such as budesonide and beclomethasone), antibiotics (usually ciprofloxacin and metronidazole), immunomodulators (mainly AZA/6-MP or methotrexate) and biological agents[ 32 , 46 ]. The aim of these treatments is to inhibit intestinal inflammation and ultimately improve the quality of life of patients with IBD[ 47 ].…”

Section: Enhancement Of the Therapeutic Effects Of Mscs On Ibdmentioning

confidence: 99%

“…Other researchers then supplemented culture media with different compounds, such as a combination of aspirin, b-fibroblast growth factor (b-FGF), all-trans retinoic acid and modified neuronal medium (MNM) or the combination of activin A, b-FGF and platelet lysates. Studies have been designed to verify whether the therapeutic effect of MSCs in vivo could be enhanced through this modification[ 32 , 97 ], and the results showed that culturing MSCs with specific pretreated culture media increase cell survival, migration, differentiation and secretory functions[ 98 ]. Yang et al [ 99 ] pretreated human UCMSCs with MNM for 24 h, washed off the MNM and replaced the culture medium with minimum essential medium.…”

Section: Enhancement Of the Therapeutic Effects Of Mscs On Ibdmentioning

confidence: 99%

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Strategies to improve the effect of mesenchymal stem cell therapy on inflammatory bowel disease

Shi¹,

Yang²

2022

World J Stem Cells

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Inflammatory bowel disease (IBD) includes Crohn’s disease and ulcerative colitis and is an idiopathic, chronic inflammatory disease of the colonic mucosa. The occurrence of IBD, causes irreversible damage to the colon and increases the risk of carcinoma. The routine clinical treatment of IBD includes drug treatment, endoscopic treatment and surgery. The vast majority of patients are treated with drugs and biological agents, but the complete cure of IBD is difficult. Mesenchymal stem cells (MSCs) have become a new type of cell therapy for the treatment of IBD due to their immunomodulatory and nutritional functions, which have been confirmed in many clinical trials. This review discusses some potential mechanisms of MSCs in the treatment of IBD, summarizes the experimental results, and provides new insights to enhance the therapeutic effects of MSCs in future applications.

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Improving the Efficacy of Mesenchymal Stem/Stromal-Based Therapy for Treatment of Inflammatory Bowel Diseases

Cited by 15 publications

References 137 publications

Human umbilical cord-derived mesenchymal stem cells ameliorate experimental colitis by normalizing the gut microbiota

Human umbilical cord-derived mesenchymal stem cells ameliorate experimental colitis by normalizing the gut microbiota

Assessment of mesenchymal stem/stromal cell-based therapy in K/BxN serum transfer-induced arthritis

Strategies to improve the effect of mesenchymal stem cell therapy on inflammatory bowel disease

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