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      A novel rat model of inflammatory bowel disease developed using a device created with a 3D printer

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          Inflammatory bowel disease (IBD) is an intractable condition. Existing models of experimental IBD are limited by their inability to create consistent ulcers between animals. The aim of this study was to develop a novel model of experimental colitis with ulcers of reproducible size.


          We used a 3D printer to fabricate a novel device containing a small window (10 × 10 mm) that could be inserted rectally to facilitate the creation of a localized ulcer in the rat intestinal mucosa. The mucosa within the window of the device was exposed to 2,4,6-trinitrobenzene sulfonic acid (TNBS) to generate ulceration. We evaluated the effects of conventional drug therapies (mesalazine and prednisolone) and local transplantation of allogeneic adipose-derived mesenchymal stem cells (ASCs) on ulcer size (measured from photographic images using image analysis software) and degree of inflammation (assessed histologically).


          The novel method produced localized, circular or elliptical ulcers that were highly reproducible in terms of size and depth. The pathological characteristics of the lesions were similar to those reported previously for conventional models of TNBS-induced colitis that show greater variation in ulcer size. Ulcer area was significantly reduced by the administration of mesalazine or prednisolone as an enema or localized injection of ASCs.


          The new model of TNBS-induced colitis, made with the aid of a device fabricated by 3D printing, generated ulcers that were reproducible in size. We anticipate that our new model of colitis will provide more reliable measures of treatment effects and prove useful in future studies of IBD therapies.


          • Adipose-derived stem cells (ASCs) are being explored as a new treatment for IBD because they can downregulate inflammation and improve tissue repair.

          • A new model of TNBS-induced colitis was developed using a custom-designed device fabricated by a 3D printer.

          • The novel model of colitis generated ulcers that were highly reproducible in size.

          • The size of the ulcer was reduced by mesalazine or prednisolone (administered as an enema) or by localized injection of ASCs.

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          Most cited references 24

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          Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle.

          Mesenchymal stem cells (MSCs) are increasingly being reported as occurring in a variety of tissues. Although MSCs from human bone marrow are relatively easy to harvest, the isolation of rodent MSCs is more difficult, thereby limiting the number of experiments in vivo. To determine a suitable cell source, we isolated rat MSCs from bone marrow, synovium, periosteum, adipose, and muscle and compared their properties for yield, expansion, and multipotentiality. After two passages, the cells in each population were CD11b (-), CD45 (-), and CD90 (+). The colony number per nucleated cells derived from synovium was 100-fold higher than that for cells derived from bone marrow. With regard to expansion potential, synovium-derived cells were the highest in colony-forming efficiency, fold increase, and growth kinetics. An in vitro chondrogenesis assay demonstrated that the pellets derived from synovium were heavier, because of their greater production of cartilage matrix, than those from other tissues, indicating their superiority in chondrogenesis. Synovium-derived cells retained their chondrogenic potential after a few passages. The Oil Red-O positive colony-rate assay demonstrated higher adipogenic potential in synovium- and adipose-derived cells. Alkaline phosphatase activity was greater in periosteum- and muscle-derived cells during calcification. The yield and proliferation potential of rat MSCs from solid tissues was much better than those from bone marrow. In particular, synovium-derived cells had the greatest potential for both proliferation and chondrogenesis, indicating their usefulness for cartilage study in a rat model.
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            Adipose-derived stromal cells: Their identity and uses in clinical trials, an update.

            In adults, adipose tissue is abundant and can be easily sampled using liposuction. Largely involved in obesity and associated metabolic disorders, it is now described as a reservoir of immature stromal cells. These cells, called adipose-derived stromal cells (ADSCs) must be distinguished from the crude stromal vascular fraction (SVF) obtained after digestion of adipose tissue. ADSCs share many features with mesenchymal stem cells derived from bone marrow, including paracrine activity, but they also display some specific features, including a greater angiogenic potential. Their angiogenic properties as well as their paracrine activity suggest a putative tumor-promoting role for ADSCs although contradictory data have been published on this issue. Both SVF cells and ADSCs are currently being investigated in clinical trials in several fields (chronic inflammation, ischemic diseases, etc.). Apart from a phase III trial on the treatment of fistula, most of these are in phase I and use autologous cells. In the near future, the end results of these trials should provide a great deal of data on the safety of ADSC use.
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              Cell sheet approach for tissue engineering and regenerative medicine.

              After the biotech medicine era, regenerative medicine is expected to be an advanced medicine that is capable of curing patients with difficult-to-treat diseases and physically impaired function. Our original scaffold-free cell sheet-based tissue engineering technology enables transplanted cells to be engrafted for a long time, while fully maintaining their viability. This technology has already been applied to various diseases in the clinical setting, including the cornea, esophagus, heart, periodontal ligament, and cartilage using autologous cells. Transplanted cell sheets not only replace the injured tissue and compensate for impaired function, but also deliver growth factors and cytokines in a spatiotemporal manner over a prolonged period, which leads to promotion of tissue repair. Moreover, the integration of stem cell biology and cell sheet technology with sufficient vascularization opens possibilities for fabrication of human three-dimensional vascularized dense and intact tissue grafts for regenerative medicine to parenchymal organs.

                Author and article information

                Regen Ther
                Regen Ther
                Regenerative Therapy
                Japanese Society for Regenerative Medicine
                13 January 2020
                June 2020
                13 January 2020
                : 14
                : 1-10
                [a ]Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Shinjyuku, Tokyo, 162-8666, Japan
                [b ]Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Shinjyuku, Tokyo, 162-8666, Japan
                [c ]Department of Integrative Bioscience and Biomedical Engineering, Graduate School of Advanced Science and Engineering, TWIns, Waseda University, Shinjyuku, Tokyo, 162-8480, Japan
                Author notes
                []Corresponding author. Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo, 162-8666, Japan. Fax: +81 3 3359 6046. yamato.masayuki@
                © 2020 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (

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