Mesenchymal Stem Cell as a Potential Therapeutic for Inflammatory Bowel Disease- Myth or Reality?

Adak, Sanjucta; Mukherjee, S.; Sen, Dwaipayan

doi:10.2174/1574888x12666170914113633

Cited by 15 publications

(13 citation statements)

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“…MSCs are characterized by active proliferation, plastic differentiation, strong immunomodulation, low immunogenicity, and abundant trophic factor production; MSCs alleviate inflammation by modulating inflammatory cytokines in inflamed tissues [23, 24]. Additionally, MSCs contribute to the regeneration of injured organs via cellular migration [17, 18].…”

Section: Discussionmentioning

confidence: 99%

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Intercellular adhesion molecule-1 enhances the therapeutic effects of MSCs in a dextran sulfate sodium-induced colitis models by promoting MSCs homing to murine colons and spleens

Wang²,

Ding

et al. 2019

Stem Cell Res Ther

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Background To investigate the therapeutic effect of intercellular adhesion molecule (ICAM)-1-modified mesenchymal stem cells (MSCs) in a mouse model of inflammatory bowel disease (IBD) induced by dextran sulfate sodium. Methods Primary MSCs and ICAM-1-overexpressing MSCs (C3 cells) were generated in vitro. The IBD mouse model was induced with drinking water containing dextran sulfate sodium for 7 days. For stem cell therapy, mice were randomly assigned to six experimental groups: the control group, IBD group, primary MSC group, C3 group, C3-vector group, and C3-ICAM-1 group. Mice were given a single injection of 1 × 10 6 primary MSCs or gene-modified MSCs via the tail vein on day 3 of DDS administration. The general conditions of the mice in each group were observed. Additionally, the pathological changes in the colon were observed and scored. Primary MSCs and gene-modified MSCs were stained with the fluorescent dye CM-DIL before injection into the tail vein of mice. The distribution of infused cells in IBD mice was observed in frozen sections. Mechanistically, the polarization of Th1, Th2, Th17, and regulatory T cells (Tregs) in the spleen was determined by flow cytometry. Moreover, the mRNA expression levels of IBD-related immune factors in splenocytes were measured by quantitative PCR. Results A single injection of MSCs promoted general recovery and reduced pathological damage in IBD mice. Additionally, ICAM-1-overexpressing MSCs had stronger therapeutic effects than ICAM-1 low MSCs. Furthermore, the in vivo distribution analysis results indicated that a higher number of ICAM-1-overexpressing MSCs homed to the colon and spleen of IBD mice. Moreover, the delivery of ICAM-1 overexpressing MSCs decreased the numbers of Th1 and Th17 cells but increased the number of Tregs in the spleen of IBD mice. The quantitative PCR analysis results revealed that an infusion of ICAM-1-overexpressing MSCs influenced the expression of spleen-derived immune factors by remarkably reducing the mRNA levels of IFN-γ and IL-17A and increasing the mRNA level of Foxp3. Conclusions Our results demonstrate that ICAM-1-modified mesenchymal stem cells (MSCs) remarkably alleviate inflammatory damage in IBD mice by promoting MSC homing to the target and immune organs. The findings suggest that ICAM-1 is required to maintain the therapeutic effects of MSCs in IBD treatment and identified a novel role of ICAM-1 in inflammatory diseases. Electronic supplementary material The online version of this article (10.1186/s13287-019-1384-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…Additionally, MSCs contribute to the regeneration of injured organs via cellular migration [17, 18]. Hence, MSCs have been tested as efficient treatments for immune-related diseases, including IBD [23, 25]. Numerous studies have shown that MSC administration may be an important treatment option for IBD .…”

Section: Discussionmentioning

confidence: 99%

Intercellular adhesion molecule-1 enhances the therapeutic effects of MSCs in a dextran sulfate sodium-induced colitis models by promoting MSCs homing to murine colons and spleens

Wang²,

Ding

et al. 2019

Stem Cell Res Ther

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“…In addition, number of clinical trials on autoimmune and inflammatory diseases have shown that allogeneic MSC administration appears to be safe and feasible in other tissues (Colmenero & Sancho-Bru, 2017). Mesenchymal stem cells are also a potential therapeutic for inflammatory diseases in other organs such as inflammatory bowel (Adak, Mukherjee, & Sen, 2017). (Li & Wu, 2015;Moodley et al, 2016).…”

Section: Role Of Mesenchymal/stromal Stem Cells (Mscs) In the Immunmentioning

confidence: 99%

Stem cells in lung repair and regeneration: Current applications and future promise

Zhu

Chen

Yang

et al. 2018

Journal Cellular Physiology

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Lung diseases are major cause of morbidity and mortality worldwide. The progress in regenerative medicine and stem cell research in the lung are currently a fast-growing research topic that can provide solutions to these major health problems. Under normal conditions, the rate of cellular proliferation is relatively low in the lung in vivo, compared to other major organ systems. Lung injury leads to the activation of stem/progenitor cell populations that re-enter the cell cycle. Yet, little is known about stem cells in the lung, despite common thoughts that these cells could play a critical role in the repair of lung injuries. Nor do we fully understand the cellular and architectural complexity of the respiratory tract, and the diverse stem/progenitor cells that are involved in the lung repair and regeneration. In this review, we discuss the conceptual framework of lung stem/progenitor cell biology, and describe lung diseases, in which stem cell manipulations may be physiologically significant. In addition, we highlight the challenges of lung stem cell-based therapy.

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“…Thus far, several clinical trials have been published, most of which are fistulizing CD and moderate-to-severe refractory luminal CD trials. 18,19 Only two studies included UC patients. 20,21 The majority of studies showed that MSC therapy had achieved reasonable success to ameliorate luminal IBD via systemic delivery and promote healing of perianal fistulas via local delivery in CD patients.…”

Section: Introductionmentioning

confidence: 99%

“…20,21 The majority of studies showed that MSC therapy had achieved reasonable success to ameliorate luminal IBD via systemic delivery and promote healing of perianal fistulas via local delivery in CD patients. 18 However, short survival time and low differentiation potential of MSCs after in vivo transplantation 22 as well as gradual deterioration of functional stem cells with age 23 limit the application of MSCs in clinical treatment. Moreover, the immunomodulatory ability of MSCs is not intrinsic and depends on the surrounding inflammatory microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Potential methods for improving the efficacy of mesenchymal stem cells in the treatment of inflammatory bowel diseases

et al. 2020

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Inflammatory bowel diseases (IBD) are a group of chronic recurrent gastrointestinal inflammatory diseases, including ulcerative colitis (UC), Crohn's disease (CD) and IBD unclassified. The pathogenesis may be related to the mucosal immune dysfunction in genetically susceptible hosts affected by environmental factors. Current therapeutic agents mainly include aminosalicylates, corticosteroids, immunosuppressive drugs and novel biological agents. The purpose of treatment is to suppress inflammation and prevent irreversible structural damage. However, long‐term application of these drugs may lead to multiple adverse effects and is not always effective. Mesenchymal stem cells (MSCs) are multipotent progenitors with low immunogenicity, which can be obtained and expanded easily. They play an important role in regulating immune responses and repairing damaged tissues in vivo. Therefore, MSCs are considered to be a promising option for the treatment of IBD. Nonetheless, there are many factors that can reduce the efficacy of MSCs, such as gradual deterioration of functional stem cells with age, low recruitment and persistence in vivo and different routes of administration. In recent years, researchers have been able to improve the efficacy of MSCs by pretreatment, genetic modification or co‐application with other substances, as well as using different tissue‐derived cells, administration methods or doses. This article reviews these methods to provide references for more effective application of MSCs in the treatment of IBD in the future.

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Mesenchymal Stem Cell as a Potential Therapeutic for Inflammatory Bowel Disease- Myth or Reality?

Abstract: Based on the current development of MSC-based clinical trials and the ever-increasing rate of in-vitro studies, with a purpose to unveil the mechanism of curative approach of these cells, MSC based therapy for IBD can be expected to achieve clinical relevance in the near future.

Cited by 15 publications

References 0 publications

Intercellular adhesion molecule-1 enhances the therapeutic effects of MSCs in a dextran sulfate sodium-induced colitis models by promoting MSCs homing to murine colons and spleens

Intercellular adhesion molecule-1 enhances the therapeutic effects of MSCs in a dextran sulfate sodium-induced colitis models by promoting MSCs homing to murine colons and spleens

Stem cells in lung repair and regeneration: Current applications and future promise

Potential methods for improving the efficacy of mesenchymal stem cells in the treatment of inflammatory bowel diseases

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