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Therapeutic Effect of Mesenchymal Stem Cells in Ulcerative Colitis: A Review on Achievements and Challenges.

ABSTRACT: The worldwide epidemiology of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), still shows an increasing trend in Asia and Iran. Despite an improvement in the treatment landscape focused on symptomatic control, long-term colectomies have not decreased over the last 10-year period. Thus, novel therapies are urgently needed in clinics to supplement the existing treatments. Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunosuppressive effects, targeting IBD as a new treatment strategy. They have recently received global attention for their use in cell transplantation due to their easy expansion and wide range of activities to be engrafted, and because they are home to the mucosa of the intestine. Moreover, MSCs are able to differentiate into epithelial and other cells that can directly promote repair in the mucosal damages in UC. It seems that there is a need to deepen our understanding to target MSCs as a promising treatment option for UC patients who are refractory to conventional therapies. Here, we overviewed the therapeutic effects of MSCs in UC and discussed the achievements and challenges in the cell transplantation of UC.

SUBMITTER: Hosseini-Asl SK

PROVIDER: S-EPMC7761671 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Therapeutic Effect of Mesenchymal Stem Cells in Ulcerative Colitis: A Review on Achievements and Challenges.

Hosseini-Asl Seyed-Kazem SK Mehrabani Davood D Karimi-Busheri Feridoun F

Journal of clinical medicine 20201203 12

The worldwide epidemiology of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), still shows an increasing trend in Asia and Iran. Despite an improvement in the treatment landscape focused on symptomatic control, long-term colectomies have not decreased over the last 10-year period. Thus, novel therapies are urgently needed in clinics to supplement the existing treatments. Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunosuppres ...[more]

PMID: 33287220

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Project description:BackgroundStem cell therapies can be a new therapeutic strategy that may rebalance anabolic and anti-resorptive effects in osteoporosis patients. Tonsil-derived mesenchymal stem cells (TMSCs) can be an alternative therapeutic source for chronic degenerative diseases including osteoporosis. MSCs acquire immune regulatory function under the inflammatory cytokines. Since interleukin (IL) 1β is known to be one of inflammatory cytokines involved in osteoporosis progression, treatment of IL1β with TMSCs may enhance immunomodulatory function and therapeutic effects of TMSCs in osteoporosis.MethodsFor IL1β priming, TMSCs were cultured in the presence of the medium containing IL1β for 1 day. Characteristics of IL1β priming TMSCs such as multipotent differentiation properties, anti-inflammatory potential, and suppression of osteoclast differentiation were assessed in vitro. For in vivo efficacy study, IL1β priming TMSCs were intravenously infused twice with ovariectomized (OVX) osteoporosis mouse model, and blood serum and bone parameters from micro computed tomography images were analyzed.ResultsIL1β priming TMSCs had an enhanced osteogenic differentiation and secreted factors that regulate both osteoclastogenesis and osteoblastogenesis. IL1β priming TMSCs also suppressed proliferation of peripheral blood mononuclear cells (PBMCs) and decreased expression of Receptor activator of nuclear factor kappa-Β ligand (RANKL) in PHA-stimulated PBMCs. Furthermore, osteoclast specific genes such as Nuclear factor of activated T cells c1 (NFATc1) were effectively down regulated when co-cultured with IL1β priming TMSCs in RANKL induced osteoclasts. In OVX mice, IL1β priming TMSCs induced low level of serum RANKL/osteoprotegerin (OPG) ratio on the first day of the last administration. Four weeks after the last administration, bone mineral density and serum Gla-osteocalcin were increased in IL1β priming TMSC-treated OVX mice. Furthermore, bone formation and bone resorption markers that had been decreased in OVX mice with low calcium diet were recovered by infusion of IL1β priming TMSCs.ConclusionIL1β priming can endow constant therapeutic efficacy with TMSCs, which may contribute to improve bone density and maintain bone homeostasis in postmenopausal osteoporosis. Therefore, IL1β priming TMSCs can be a new therapeutic option for treating postmenopausal osteoporosis.

Project description:BackgroundMesenchymal stem cells (MSCs) therapy is a novel treatment strategy for cancer and a wide range of diseases with an excessive immune response such as ulcerative colitis (UC), due to its powerful immunomodulatory properties and its capacity for tissue regeneration and repair. One of the promising therapeutic options can focus on MSC-secreted exosomes (MSC-Exo), which have been identified as a type of paracrine interaction. In light of a wide variety of recent experimental studies, the present review aims to seek the recent research advances of therapies based on the MSC-Exo for treating UC and colorectal cancer (CRC).MethodsA systematic literature search in MEDLINE, Scopus, and Google Scholar was performed from inception to December 2021 using the terms [("colorectal cancer" OR "bowel cancer" OR "colon cancer" OR "rectal cancer") AND (exosome) AND (stem cell) AND ("inflammatory bowel disease" OR "Crohn's disease" OR "colitis")] in titles and abstracts.FindingsExosomes derived from various sources of MSCs, including human umbilical cord-derived MSCs (hUC-MSCs), human adipose-derived MSCs (hAD-MSCs), human bone marrow-derived MSCs (hBM-MSCs), and olfactory ecto-MSCs (OE-MSCs), have shown the protective role against UC and CRC. Exosomes from hUC-MSCs, hBM-MSCs, AD-MSCs, and OE-MSCs have been found to ameliorate the experimental UC through suppressing inflammatory cells including macrophages, Th1/Th17 cells, reducing the expression of proinflammatory cytokines, as well as inducing the anti-inflammatory function of Treg and Th2 cells and enhancing the expression of anti-inflammatory cytokines. In addition, hBM-MSC-Exo and hUC-MSC-Exo containing tumor-suppressive miRs (miR-3940-5p/miR-22-3p/miR-16-5p) have been shown to suppress proliferation, migration, and invasion of CRC cells via regulation of RAP2B/PI3K/AKT signaling pathway and ITGA2/ITGA6.Key messagesThe MSC-Exo can exert beneficial effects on UC and CRC through two different mechanisms including modulating immune responses and inducing anti-tumor responses, respectively.

Dataset Information

Therapeutic Effect of Mesenchymal Stem Cells in Ulcerative Colitis: A Review on Achievements and Challenges.

Publications

Therapeutic Effect of Mesenchymal Stem Cells in Ulcerative Colitis: A Review on Achievements and Challenges.

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