The Therapeutic Effects of Adipose-Derived Stem Cells and Recombinant Peptide Pieces on Mouse Model of DSS Colitis

Abstract

Cell therapies using adipose-derived stem cells (ADSCs) have been used to treat inflammatory bowel disease (IBD) in human and dog. We previously reported the CellSaic technique, which uses a recombinant scaffold to enhance the efficacy of cell therapy. To examine whether this technique can be applied to cell therapy for colitis, we evaluated the efficacy of CellSaic in colitis mouse models. Colitis mouse models were developed by administering dextran sulfate sodium (DSS) to C57BL/6 mice for 7 days. Then CellSaic comprising human/canine ADSCs (1.2 × 106 cells) or human/canine ADSCs only (1.2 × 106 cells) were administered to the mice. The body weights were measured, and the colon length measurements and histological evaluations were conducted at 7 days after administration. After in vitro culture of human ADSC (hADSC) CellSaic and hADSC spheroids in medium containing TNFα, the levels of the anti-inflammatory protein TSG-6 in each supernatant were measured. Furthermore, we conducted tumorigenicity and general toxicity tests of canine ADSC (cADSC) CellSaic in NOG mice for 8 weeks. In the colitis mouse models, the ADSC CellSaic group presented recovery of body weight and colon length compared with the ADSC-only group. Histological analysis showed that ADSC CellSaic decreased the number of inflammatory cells and repaired ulceration. In vitro, hADSC CellSaic secreted 3.1-fold more TSG-6 than the hADSCs. In addition, tumorigenicity and general toxicity of cADSC CellSaic were not observed. This study suggests that human and canine ADSC CellSaic has a therapeutic effect of colitis in human and dogs.

Co-Microencapsulation of Islets and MSC CellSaics, Mosaic-Like Aggregates of MSCs and Recombinant Peptide Pieces, and Therapeutic Effects of Their Subcutaneous Transplantation on Diabetes

“…It is known that MSCs secrete anti-inflammatory cytokines (IL-10, TGF-α, IDO, TSG-6, etc.) [15][16][17]31], and we have confirmed that MSC CellSaics secreted 3.1-fold more anti-inflammatory cytokine TSG-6 in response to concentration of inflammatory cytokine TNF-α than the MSC spheroids [20]. In reference [34], it is reported that transplantation of ALG-PLO microencapsulated islets trigger inflammation by increasing the TNF-α concentration at the transplantation site.…”

“…Mesenchymal stem cells (MSCs) are promising options as the cells comprising CellSaics for subcutaneous transplantation since they have revascularization, anti-inflammatory, and immunomodulatory abilities [14][15][16][17] and are known to enhance islet function when co-transplanted with them [18,19]. Our previous study demonstrated the continuous release of angiogenic factors and anti-inflammatory cytokines via a combination of MSCs and CellSaics (MSC CellSaics) [13,20]. Furthermore, the subcutaneous co-transplantation of the MSC CellSaics and islets into immunodeficient mice was shown to have higher therapeutic efficiency compared to co-transplantation of MSCs and islets [13].…”

In Vitro Cultures of Adipose-Derived Stem Cells: An Overview of Methods, Molecular Analyses, and Clinical Applications

“…Because of its anti-inflammatory properties, ASC transplantation has appeared to be an effective method for treatment of inflammatory bowel diseases in animal models [ 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 ]. It was found that ASC administration significantly reduced the secretion of proinflammatory cytokines (tumor necrosis factor-α, interleukin-12, and vascular endothelial growth factor), and improved the clinical disease score and histological parameters in experimentally induced models of murine colitis [ 103 , 104 , 105 , 108 , 109 , 110 ]. The ASC infusion resulted in a decrease in both clinical inflammatory bowel disease activity index and canine chronic enteropathy clinical activity index, in a group of treated dogs.…”

A New Islet Transplantation Method Combining Mesenchymal Stem Cells with Recombinant Peptide Pieces, Microencapsulated Islets, and Mesh Bags

“…MSC-CellSaic enhances the function of microencapsulated pancreatic islets by inducing angiogenesis and suppressing the inflammatory response. It was previously reported that the anti-inflammatory effect of MSC-CellSaic was enhanced over that of non-CellSaic MSCs [ 25 ]. Making MSCs CellSaic secretes more of the anti-inflammatory cytokine TSG-6, which is an important cytokine that exerts its effects in various inflammatory models [ 26 ].…”