Early injection of human adipose tissue-derived mesenchymal stem cell after inflammation ameliorates dextran sulfate sodium-induced colitis in mice through the induction of M2 macrophages and regulatory T cells

Kawata, Yuzo; Tsuchiya, Atsunori; Seino, Satoshi; Watanabe, Yusuke; Kojima, Yuichi; Ikarashi, Shunzo; Tominaga, Kentaro; Yokoyama, Junji; Yamagiwa, Satoshi; Terai, Shuji

doi:10.1007/s00441-018-02981-w

Cited by 40 publications

(33 citation statements)

References 26 publications

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“…Our results were also consistent with a report showing that MSCs exhibit increased therapeutic effects during the inflammatory phase than during the reparative and remodeling phases. 17 In addition, dexamethasone weakens the therapeutic effects of MSCs in a mouse model of CCl 4 -induced liver injury. The concept that appropriate cell injection timing and host inflammatory conditions induce the maximum therapeutic effect is important when MSCs are used for the treatment of inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

Effects of Human Adipose Tissue-Derived and Umbilical Cord Tissue-Derived Mesenchymal Stem Cells in a Dextran Sulfate Sodium-Induced Mouse Model

Ikarashi

Tsuchiya

Kawata

et al. 2019

BioResearch Open Access

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Mesenchymal stem cells (MSCs) can be acquired from medical waste. MSCs are easily expanded and have multiple functions, including anti-inflammatory effects. We evaluated the effects of human adipose tissue-derived MSCs (AD-MSCs) and umbilical cord tissue-derived MSCs (UC-MSCs) in a dextran sulfate sodium (DSS)-induced mouse model. Human AD-MSCs and UC-MSCs (1 • 10 6 cells) were injected intravenously into a 7-day DSS-induced colitis model. The therapeutic effects of cell origin, injection timing, and supernatants obtained from MSC cultures were evaluated. We also analyzed messenger RNA (mRNA) expression in MSCs, tissues, and intestinal flora. AD-MSCs and UC-MSCs were found to show strong anti-inflammatory effects when injected on day 3 in a mouse model. On day 11, the mRNA levels of inflammatory factors in colon tissues were significantly decreased after injection of MSCs on day 3. Supernatants from MSCs culture decreased mRNA levels of tumor necrosis factor (Tnf)-a, but had reduced therapeutic effects compared with MSC cell injection. RNA sequencing using colon tissues obtained the day after cell injection revealed changes in the TNF-a/nuclear factor-jB and T cell receptor signaling pathways. Additional analyses showed that several factors, including chromosome 10 open reading frame 54, stanniocalcin-1, and TNF receptor superfamily member 11b were increased in MSCs after adding serum from DSS colitis mice. Furthermore, both AD-MSCs and UC-MSCs maintained the balance of intestinal flora. In conclusion, AD-MSCs and UC-MSCs showed therapeutic effects against inflammation after early cell injection while maintaining the intestinal flora. Although supernatants showed therapeutic effects, cell injection was more effective against inflammation.

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Section: Discussionmentioning

confidence: 99%

Effects of Human Adipose Tissue-Derived and Umbilical Cord Tissue-Derived Mesenchymal Stem Cells in a Dextran Sulfate Sodium-Induced Mouse Model

Ikarashi

Tsuchiya

Kawata

et al. 2019

BioResearch Open Access

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“…Of these functions, MSCs are most commonly applied to achieve anti-inflammation effects. MSCs produce various factors such as nitric oxide/indoleamine 2,3-dioxygenase, interleukin (IL)-10, tumor necrosis factor-inducible gene-6, and prostaglandin E2; inhibit T cell activation and expansion; induce regulatory T cells; alter the polarity of macrophages to the anti-inflammatory phenotype; and control the function of dendritic cells, B cells, and natural killer cells [18, 19]. Another important characteristic of MSCs is that they generally have low immunogenicity.…”

Section: General Information Of Mscsmentioning

confidence: 99%

Mesenchymal stem cell therapies for liver cirrhosis: MSCs as “conducting cells” for improvement of liver fibrosis and regeneration

et al. 2019

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Mesenchymal stem cells (MSCs) can be cultured relatively easily and can be obtained not only from the bone marrow, but also from medical waste such as adipose tissue and umbilical cord tissue. Because of its low antigenicity, allogeneic MSC injection is safe. MSCs have been evaluated in more than 900 clinical trials in a variety of fields, with more than 50 clinical trials related to liver diseases. Experiments have suggested that MSCs function as “conducting cells” to affect various “effective cells” such as T cells, B cells, and macrophages. Recent clinical trials have focused on allogeneic MSCs. Thus, studies are needed to determine the most effective cell source, culture conditions, cell numbers, administration frequency, administration route, cost, safety, and liver disease treatments. Recently, the functions of exosomes have gained attention, and cell-free therapy may become possible as an alternative therapy for liver disease. In this review, we introduce general information, mechanism, representative clinical study data, recently started or planned clinical trials, and possibility of cell-free therapy of MSCs.

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“…Similar therapeutic effects are described for both WAT and ADSCs, yet there is a trend in regenerative and immunomodulatory medicine toward the utilization of the supposedly more versatile ADSCs. They are thought to be the most promising cells of the SVF regarding medical benefits [12][13][14][15][16][17], and their molecular features make them promising candidate cells, not only in the field of regenerative medicine, but also for the treatment of inflammatory-related disorders [7,[18][19][20][21][22][23][24]. ADSCs can exert immunomodulation through direct contact with immune cells or by secretion of paracrine factors [5,7,8].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, ADSCs have the capacity to interfere with the adaptive immune system [27][28][29]. For clinical purposes, ADSCs have been used as anti-inflammatory "bioreactors" in the case of inflammatory bowel diseases, osteoarthritis, diabetes mellitus, chronic wounds and scar treatment [13][14][15]19,[30][31][32]. Nevertheless, there is still some ambiguity regarding the utilization of ADSCs as a cellular treatment option.…”

Section: Introductionmentioning

confidence: 99%

Differences in the Inflammatory Response of White Adipose Tissue and Adipose-Derived Stem Cells

Taha

Volkmer

Haas

et al. 2020

IJMS

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The application of liposuctioned white adipose tissue (L-WAT) and adipose-derived stem cells (ADSCs) as a novel immunomodulatory treatment option is the currently subject of various clinical trials. Because it is crucial to understand the underlying therapeutic mechanisms, the latest studies focused on the immunomodulatory functions of L-WAT or ADSCs. However, studies that examine the specific transcriptional adaptation of these treatment options to an extrinsic inflammatory stimulus in an unbiased manner are scarce. The aim of this study was to compare the gene expression profile of L-WAT and ADSCs, when subjected to tumor necrosis factor alpha (TNFα), and to identify key factors that might be therapeutically relevant when using L-WAT or ADSCs as an immuno-modulator. Fat tissue was harvested by liposuction from five human donors. ADSCs were isolated from the same donors and shortly subjected to expansion culture. L-WAT and ADSCs were treated with human recombinant TNFα, to trigger a strong inflammatory response. Subsequently, an mRNA deep next-generation sequencing was performed to evaluate the different inflammatory responses of L-WAT and ADSCs. We found significant gene expression changes in both experimental groups after TNFα incubation. However, ADSCs showed a more homogenous gene expression profile by predominantly expressing genes involved in immunomodulatory processes such as CCL19, CCL5, TNFSF15 and IL1b when compared to L-WAT, which reacted rather heterogeneously. As RNA sequencing between L-WAT and ADSCS treated with TNFα revealed that L-WAT responded very heterogeneously to TNFα treatment, we therefore conclude that ADSCs are more reliable and predictable when used therapeutically. Our study furthermore yields insight into potential biological processes regarding immune system response, inflammatory response, and cell activation. Our results can help to better understand the different immunomodulatory effects of L-WAT and ADSCs.

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Early injection of human adipose tissue-derived mesenchymal stem cell after inflammation ameliorates dextran sulfate sodium-induced colitis in mice through the induction of M2 macrophages and regulatory T cells

Cited by 40 publications

References 26 publications

Effects of Human Adipose Tissue-Derived and Umbilical Cord Tissue-Derived Mesenchymal Stem Cells in a Dextran Sulfate Sodium-Induced Mouse Model

Effects of Human Adipose Tissue-Derived and Umbilical Cord Tissue-Derived Mesenchymal Stem Cells in a Dextran Sulfate Sodium-Induced Mouse Model

Mesenchymal stem cell therapies for liver cirrhosis: MSCs as “conducting cells” for improvement of liver fibrosis and regeneration

Differences in the Inflammatory Response of White Adipose Tissue and Adipose-Derived Stem Cells

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