Combined Rg1 and adipose-derived stem cells Alleviate DSS-induced colitis in a mouse model

Abstract Background Inflammatory bowel diseases (IBDs) including Crohn's disease and ulcerative colitis are chronic inflammatory disorders that can affect the entire gastrointestinal tract and the colonic mucosa, no medical or surgical cure for IBD, and all have side effects that limit their use, exhibit a high necessity for new therapeutic strategies. Adipose-derived stem cells (ADSC) therapy represents a promising option for the treatment of IBD. Rg1 Previous study indicated that ginsenoside (Rg1) can ameliorate inflammatory disease such as colitis by inhibiting the binding of LPS to TLR4 on macrophages and restoring the Th17/Treg imbalance [1]. In this study, we investigated whether Rg1 can enhance the effect of ADSC on DSS-induced colitis in a mouse model. Methods Mice with dextran sulfate sodium-induced colitis were injected intravenously with ADSC and administered with Rg1 by gavage. Body weight change, colon length, H&E staining were used to evaluate colon inflammation severity in a DSS-induced colitis Serum were collected for Cytokine detection by ELISA. The proportion and FMI of immune cells in spleen were analyzed by flow cytometry. Stool DNA was extracted for 16S rRNA gene sequencing. Results Rg1 and ADSC showed significantly ameliorated colon inflammation, such as body weight loss, shortening of colon length, histology score. Rg1 and ADSC treatment downregulated the level of proinflammatory cytokines, including IL-1β, TNF-α, IL-6, IL-4 and IL-17A and upregulated the immunosuppressive cytokine IL-10 in serum. We observed that the structure of the microbial community in Rg1 + ADSC group were significantly changed compared to that of ADSC and Rg1 groups, respectively. Additionally, Rg1 and ADSC treated selectively upregulated the percentage of spleen regulatory T (Treg) cells as well as downregulated the frequency of T helper type 17 (Th17) cells, ameliorating the Treg/Th17 balance to maintain intestinal homeostasis. Furthermore, we found the combination of ADSC + Rg1 groups showed more efficiently than that of ADSC and Rg1 alone, respectively, which indicates that the regulation effect of Rg1 on gut microbiome may enhance the effects of ADSCs in restoring immune balance. Conclusions Our study indicated that the combination of Rg1 and ADSC can alleviate dextran sulfate sodium-induced colitis more efficiently than that of ADSC alone, Rg1 can enhance the effect of ADSC on DSS-induced colitis in a mouse model.

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

BioResearch Open Access ◽

10.1089/biores.2019.0022 ◽

2019 ◽

Vol 8 (1) ◽

pp. 185-199 ◽

Cited By ~ 3

Author(s):

Shunzo Ikarashi ◽

Atsunori Tsuchiya ◽

Yuzo Kawata ◽

Yuichi Kojima ◽

Takayuki Watanabe ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Mouse Model ◽

Umbilical Cord ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Human Adipose Tissue ◽

Umbilical Cord Tissue

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Conditioned secretome of adipose-derived stem cells improves dextran sulfate sodium-induced colitis in mice

World Journal of Gastroenterology ◽

10.3748/wjg.v27.i23.3342 ◽

2021 ◽

Vol 27 (23) ◽

pp. 3342-3356

Author(s):

Seunghun Lee ◽

Jeonghoon Heo ◽

Eun-Kyung Ahn ◽

Jae Hyun Kim ◽

Young-Ho Kim ◽

...

Keyword(s):

Stem Cells ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Adipose Derived Stem Cells

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Characteristics of Colon Crypt Stem Cells in Preserved Epithelial Cell Clumps in Dextran Sulfate Sodium-induced Mouse Model of Ulcerative Colitis

10.21203/rs.3.rs-144494/v1 ◽

2021 ◽

Author(s):

Mio Kobayashi ◽

Risako Yamashita ◽

Ryo Ichikawa ◽

Makoto Shibutani ◽

Toshinori Yoshida

Keyword(s):

Ulcerative Colitis ◽

Stem Cells ◽

Stem Cell ◽

Mouse Model ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Stem Cell Marker ◽

Stem Cell Markers ◽

Cell Marker ◽

Cell Markers

Abstract Crypt stem cells rescue the colorectum from refractory ulcers in ulcerative colitis (UC). We previously reported that clumps of a few epithelial cells were scattered in ulcer regions in a dextran sulfate sodium (DSS)-induced mouse model of UC; however, the origin of the clumps is unknown. We determined the immunohistochemical expression of stem-cell markers in the epithelial clumps in female Balb/c mice administered DSS in drinking water for 6 days, followed by withdrawal of DSS for 6 days. Similar to the characteristics of UC, the ulcers were more severe in the distal region close to the anus than in the proximal region of the colorectum. Quantitative analyses revealed that the epithelial clumps appeared in relation to the severity of ulcer, and they expressed the cell adhesion molecules E-cadherin and β-catenin. Among stem cell markers, the epithelial clumps primarily expressed + 5 cell marker Dll1, followed by + 4 cell marker Bmi1 and crypt stem cell marker Lgr5 in that order. Nuclear expression of Sox9, but not Ki-67 and β-catenin was identified in the clumps. The present results suggest that the epithelial clumps comprised crypt-derived stem cells with the potential to regenerate crypts, which could serve as a potential treatment strategy for UC.

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Shikonin inhibits colitis-associated colorectal dysplasias in a mouse model of azoxymethane/dextran sulfate sodium colitis

Planta Medica ◽

10.1055/s-0032-1320447 ◽

2012 ◽

Vol 78 (11) ◽

Author(s):

JL Ríos ◽

A Martí ◽

I Andújar ◽

RM Giner ◽

MC Recio

Keyword(s):

Mouse Model ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium

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Therapeutic Potential of Magnetic Nanoparticle-Based Human Adipose-Derived Stem Cells in a Mouse Model of Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22020654 ◽

2021 ◽

Vol 22 (2) ◽

pp. 654

Author(s):

Ka Young Kim ◽

Keun-A Chang

Keyword(s):

Parkinson’S Disease ◽

Stem Cells ◽

Parkinson's Disease ◽

Magnetic Nanoparticles ◽

Substantia Nigra ◽

Mouse Model ◽

Magnetic Nanoparticle ◽

Imaging System ◽

Therapeutic Potential ◽

Adipose Derived Stem Cells

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra. Several treatments for PD have focused on the management of physical symptoms using dopaminergic agents. However, these treatments induce various adverse effects, including hallucinations and cognitive impairment, owing to non-targeted brain delivery, while alleviating motor symptoms. Furthermore, these therapies are not considered ultimate cures owing to limited brain self-repair and regeneration abilities. In the present study, we aimed to investigate the therapeutic potential of human adipose-derived stem cells (hASCs) using magnetic nanoparticles in a 6-hydroxydopamine (6-OHDA)-induced PD mouse model. We used the Maestro imaging system and magnetic resonance imaging (MRI) for in vivo tracking after transplantation of magnetic nanoparticle-loaded hASCs to the PD mouse model. The Maestro imaging system revealed strong hASCs signals in the brains of PD model mice. In particular, MRI revealed hASCs distribution in the substantia nigra of hASCs-injected PD mice. Behavioral evaluations, including apomorphine-induced rotation and rotarod performance, were significantly recovered in hASCs-injected 6-OHDA induced PD mice when compared with saline-treated counterparts. Herein, we investigated whether hASCs transplantation using magnetic nanoparticles recovered motor functions through targeted brain distribution in a 6-OHDA induced PD mice. These results indicate that magnetic nanoparticle-based hASCs transplantation could be a potential therapeutic strategy in PD.

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Longitudinal Microbiome Analysis in a Dextran Sulfate Sodium-Induced Colitis Mouse Model

Microorganisms ◽

10.3390/microorganisms9020370 ◽

2021 ◽

Vol 9 (2) ◽

pp. 370

Author(s):

Hyunjoon Park ◽

Soyoung Yeo ◽

Seokwon Kang ◽

Chul Sung Huh

Keyword(s):

Mouse Model ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Intestinal Bleeding ◽

Cross Sectional ◽

Microbiome Analysis ◽

Inflammatory Bowel ◽

Factor Design ◽

The Individual

The role of the gut microbiota in the pathogenesis of inflammatory bowel disease (IBD) has been in focus for decades. Although metagenomic observations in patients/animal colitis models have been attempted, the microbiome results were still indefinite and broad taxonomic presumptions were made due to the cross-sectional studies. Herein, we conducted a longitudinal microbiome analysis in a dextran sulfate sodium (DSS)-induced colitis mouse model with a two-factor design based on serial DSS dose (0, 1, 2, and 3%) and duration for 12 days, and four mice from each group were sacrificed at two-day intervals. During the colitis development, a transition of the cecal microbial diversity from the normal state to dysbiosis and dynamic changes of the populations were observed. We identified genera that significantly induced or depleted depending on DSS exposure, and confirmed the correlations of the individual taxa to the colitis severity indicated by inflammatory biomarkers (intestinal bleeding and neutrophil-derived indicators). Of note, each taxonomic population showed its own susceptibility to the changing colitis status. Our findings suggest that an understanding of the individual susceptibility to colitis conditions may contribute to identifying the role of the gut microbes in the pathogenesis of IBD.

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Extracellular vesicles derived from adipose-derived stem cells accelerate diabetic wound healing by suppressing the expression of matrix metalloproteinase-9

Current Pharmaceutical Biotechnology ◽

10.2174/1389201022666210719154009 ◽

2021 ◽

Vol 22 ◽

Author(s):

Jiang-wen Wang ◽

Yuan-zheng Zhu ◽

Xuan Hu ◽

Jia-ying Nie ◽

Zhao-hui Wang ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mouse Model ◽

Adipose Derived Stem Cells ◽

Collagen Deposition ◽

Diabetic Wound ◽

Diabetic Wound Healing ◽

Diabetic Wounds ◽

Metalloproteinase 9

Background: The healing of diabetic wounds is poor due to a collagen deposition disorder. Matrix metalloproteinase-9 (MMP-9) is closely related to collagen deposition in the process of tissue repair. Many studies have demonstrated that extracellular vesicles derived from adipose-derived stem cells (ADSC-EVs) promote diabetic wound healing by enhancing collagen deposition. Objective: In this study, we explored if ADSC-EVs could downregulate the expression of MMP-9 in diabetic wounds and promote wound healing by improving collagen deposition. The potential effects of ADSC-EVs on MMP-9 and diabetic wound healing were tested both in vitro and in vivo. Methods: We first evaluated the effect of ADSC-EVs on the proliferation and MMP-9 secretion of HaCaT cells treated with advanced glycation end product-bovine serum albumin (AGE-BSA), using CCK-8 western blot and MMP-9 enzyme-linked immunosorbent assay(ELISA). Next, the effect of ADSC-EVs on the healing, re-epithelialisation, collagen deposition, and MMP-9 concentration in diabetic wound fluids was evaluated in an immunodeficient mouse model via MMP-9 ELISA and haematoxylin and eosin, Masson’s trichrome, and immunofluorescence staining for MMP-9. Results: In vitro, ADSC-EVs promoted the proliferation and MMP-9 secretion of HaCaT cells.In vivo, ADSC-EVs accelerated diabetic wound healing by improving re-epithelialisation and collagen deposition and by inhibiting the expression of MMP-9. Conclusion: ADSC-EVs possessed the healing of diabetic wounds in a mouse model by inhibiting downregulating MMP-9 and improving collagen deposition.Thus ,ADSC-EVs are a promising candidate for the treatment of diabetic wounds .

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An electrochemically deposited collagen wound matrix combined with adipose-derived stem cells improves cutaneous wound healing in a mouse model of type 2 diabetes

Journal of Biomaterials Applications ◽

10.1177/0885328218803754 ◽

2018 ◽

Vol 33 (4) ◽

pp. 553-565 ◽

Cited By ~ 4

Author(s):

Nicole Edwards ◽

Denis Feliers ◽

Qingwei Zhao ◽

Randolph Stone ◽

Robert Christy ◽

...

Keyword(s):

Type 2 Diabetes ◽

Stem Cells ◽

Mouse Model ◽

Chronic Wounds ◽

High Porosity ◽

Adipose Derived Stem Cells ◽

Clinical Issue ◽

Wound Matrix ◽

Electrochemically Deposited

Chronic wounds complicated by diabetes are a significant clinical issue, and their occurrence is expected to continue to rise due to an increased prevalence of diabetes mellitus, especially type 2 diabetes. Diabetic wounds frequently lead to nonhealing ulcers, and often eventually result in limb amputation due to the high risk of infection of the chronic wound. Here, we present a tissue-engineered treatment that combines a novel electrochemically deposited collagen wound matrix and human adipose-derived stem cells. The matrix fabrication process is optimized for voltage and time, and the final collagen biomaterial is thoroughly characterized. This collagen material possesses high tensile strength, high porosity, and excellent biocompatibility and cellular proliferation capabilities. Human adipose-derived stem cells were seeded onto the collagen wound matrix and this construct is investigated in a full thickness excisional wound in a mouse model of type 2 diabetes. This novel treatment is shown to stimulate excellent healing and tissue regeneration, resulting in increased granulation tissue formation, epidermal thickness, and overall higher quality tissue reformation. Both the collagen wound matrix alone and collagen wound matrix in combination with adipose derived stem cells appeared to be excellent treatments for diabetic skin wounds, and in the future can also be optimized to treat other injuries such as burns, blast injuries, surgical incisions, and other traumatic injuries.

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