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Combinational Treatment Involving Decellularized Extracellular Matrix Hydrogels With Mesenchymal Stem Cells Increased the Efficacy of Cell Therapy in Pancreatitis
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- Hideaki Kojima
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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- Hiroko Kushige
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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- Hiroshi Yagi
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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- Takayuki Nishijima
- Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan
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- Nobuko Moritoki
- Electron Microscope Laboratory, Keio University School of Medicine, Tokyo, Japan
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- Narihito Nagoshi
- Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan
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- Yutaka Nakano
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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- Masayuki Tanaka
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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- Shutaro Hori
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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- Yasushi Hasegawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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- Yuta Abe
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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- Minoru Kitago
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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- Masaya Nakamura
- Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan
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- Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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Description
<jats:p> Cell transplantation using mesenchymal stem cells (MSCs) has emerged as a promising approach to repairing and regenerating injured or impaired organs. However, the survival and retention of MSCs following transplantation remain a challenge. Therefore, we investigated the efficacy of co-transplantation of MSCs and decellularized extracellular matrix (dECM) hydrogels, which have high cytocompatibility and biocompatibility. The dECM solution was prepared by enzymatic digestion of an acellular porcine liver scaffold. It could be gelled and formed into porous fibrillar microstructures at physiological temperatures. MSCs expanded three-dimensionally in the hydrogel without cell death. Compared to the 2-dimensional cell culture, MSCs cultured in the hydrogel showed increased secretion of hepatocyte growth factor (HGF) and tumor necrosis factor-inducible gene 6 protein (TSG-6), both of which are major anti-inflammatory and anti-fibrotic paracrine factors of MSCs, under TNFα stimulation. In vivo experiments showed that the co-transplantation of MSCs with dECM hydrogel improved the survival rate of engrafted cells compared to those administered without the hydrogel. MSCs also demonstrated therapeutic effects in improving inflammation and fibrosis of pancreatic tissue in a dibutyltin dichloride (DBTC)-induced rat pancreatitis model. Combinational use of dECM hydrogel with MSCs is a new strategy to overcome the challenges of cell therapy using MSCs and can be used for treating chronic inflammatory diseases in clinical settings. </jats:p>
Journal
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- Cell Transplantation
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Cell Transplantation 32 2023-01
SAGE Publications