Human Umbilical Cord Mesenchymal Stem Cells Ameliorate Mice Trinitrobenzene Sulfonic Acid (TNBS)-Induced Colitis
Mesenchymal stem cells (MSCs), which are poorly immunogenic and have potent immunosuppressive activities, have emerged as a promising candidate for cellular therapeutics for the treatment of disorders caused by abnormal immune responses. In this study we investigated whether human umbilical cord-der...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2011-10-01
|
| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368910X557245 |
| _version_ | 1818409841020895232 |
|---|---|
| author | Lu Liang Chunlan Dong Xiaojun Chen Zhihong Fang Jie Xu Meng Liu Xiaoguang Zhang Dong Sheng Gu Ding Wang Weiting Du Delin Zhu Ph.D. Zhong Chao Han M.D., Ph.D. |
| author_facet | Lu Liang Chunlan Dong Xiaojun Chen Zhihong Fang Jie Xu Meng Liu Xiaoguang Zhang Dong Sheng Gu Ding Wang Weiting Du Delin Zhu Ph.D. Zhong Chao Han M.D., Ph.D. |
| author_sort | Lu Liang |
| collection | DOAJ |
| description | Mesenchymal stem cells (MSCs), which are poorly immunogenic and have potent immunosuppressive activities, have emerged as a promising candidate for cellular therapeutics for the treatment of disorders caused by abnormal immune responses. In this study we investigated whether human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could ameliorate colitis in a trinitrobenzene sulfonic acid (TNBS)-induced colitis model. TNBS-treated colitic mice were infused with hUC-MSCs or vehicle control. The mice were sacrificed on day 1, 3, and 5 after infusion, and their clinical and pathological conditions were evaluated by body weight, colon length, and histological analysis. The expression levels of proinflammatory cytokine proteins in colon were examined by ELISA. The homing of hUC-MSCs was studied by live in vivo imaging and immunofluorescent microscopy. hUC-MSCs were found to migrate to the inflamed colon and effectively treated the colitic mice with improved clinical and pathological signs. The levels of IL-17 and IL-23 as well as IFN-γ and IL-6 were significantly lower in the colon tissues of the hUC-MSC-treated mice in comparison with the vehicle-treated mice. Coculture experiments showed that hUC-MSCs not only could inhibit IFN-γ expression but also significantly inhibit IL-17 production by lamina propria mononuclear cells (LPMCs) or splenocytes of the colitic mice or by those isolated from normal animals and stimulated with IL-23. Systemically infused hUC-MSCs could home to the inflamed colon and effectively ameliorate colitis. In addition to the known suppressive effects on Th1-type immune responses, hUC-MSC-mediated modulation of IL-23/IL-17 regulated inflammatory reactions also plays an important role in the amelioration of colitis. |
| first_indexed | 2024-12-14T10:06:02Z |
| format | Article |
| id | doaj.art-25c7c760740f4798bf74a0f21befa919 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-14T10:06:02Z |
| publishDate | 2011-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-25c7c760740f4798bf74a0f21befa9192022-12-21T23:07:08ZengSAGE PublishingCell Transplantation0963-68971555-38922011-10-012010.3727/096368910X557245Human Umbilical Cord Mesenchymal Stem Cells Ameliorate Mice Trinitrobenzene Sulfonic Acid (TNBS)-Induced ColitisLu Liang0Chunlan Dong1Xiaojun Chen2Zhihong Fang3Jie Xu4Meng Liu5Xiaoguang Zhang6Dong Sheng Gu7Ding Wang8Weiting Du9Delin Zhu Ph.D.10Zhong Chao Han M.D., Ph.D.11State Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS&PUMC), Tianjin, PR ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS&PUMC), Tianjin, PR ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS&PUMC), Tianjin, PR ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS&PUMC), Tianjin, PR ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS&PUMC), Tianjin, PR ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS&PUMC), Tianjin, PR ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS&PUMC), Tianjin, PR ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS&PUMC), Tianjin, PR ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS&PUMC), Tianjin, PR ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS&PUMC), Tianjin, PR ChinaNational Engineering Research Center of Cell Products, AmCellGene Co. Ltd., Tianjin, PR ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS&PUMC), Tianjin, PR ChinaMesenchymal stem cells (MSCs), which are poorly immunogenic and have potent immunosuppressive activities, have emerged as a promising candidate for cellular therapeutics for the treatment of disorders caused by abnormal immune responses. In this study we investigated whether human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could ameliorate colitis in a trinitrobenzene sulfonic acid (TNBS)-induced colitis model. TNBS-treated colitic mice were infused with hUC-MSCs or vehicle control. The mice were sacrificed on day 1, 3, and 5 after infusion, and their clinical and pathological conditions were evaluated by body weight, colon length, and histological analysis. The expression levels of proinflammatory cytokine proteins in colon were examined by ELISA. The homing of hUC-MSCs was studied by live in vivo imaging and immunofluorescent microscopy. hUC-MSCs were found to migrate to the inflamed colon and effectively treated the colitic mice with improved clinical and pathological signs. The levels of IL-17 and IL-23 as well as IFN-γ and IL-6 were significantly lower in the colon tissues of the hUC-MSC-treated mice in comparison with the vehicle-treated mice. Coculture experiments showed that hUC-MSCs not only could inhibit IFN-γ expression but also significantly inhibit IL-17 production by lamina propria mononuclear cells (LPMCs) or splenocytes of the colitic mice or by those isolated from normal animals and stimulated with IL-23. Systemically infused hUC-MSCs could home to the inflamed colon and effectively ameliorate colitis. In addition to the known suppressive effects on Th1-type immune responses, hUC-MSC-mediated modulation of IL-23/IL-17 regulated inflammatory reactions also plays an important role in the amelioration of colitis.https://doi.org/10.3727/096368910X557245 |
| spellingShingle | Lu Liang Chunlan Dong Xiaojun Chen Zhihong Fang Jie Xu Meng Liu Xiaoguang Zhang Dong Sheng Gu Ding Wang Weiting Du Delin Zhu Ph.D. Zhong Chao Han M.D., Ph.D. Human Umbilical Cord Mesenchymal Stem Cells Ameliorate Mice Trinitrobenzene Sulfonic Acid (TNBS)-Induced Colitis Cell Transplantation |
| title | Human Umbilical Cord Mesenchymal Stem Cells Ameliorate Mice Trinitrobenzene Sulfonic Acid (TNBS)-Induced Colitis |
| title_full | Human Umbilical Cord Mesenchymal Stem Cells Ameliorate Mice Trinitrobenzene Sulfonic Acid (TNBS)-Induced Colitis |
| title_fullStr | Human Umbilical Cord Mesenchymal Stem Cells Ameliorate Mice Trinitrobenzene Sulfonic Acid (TNBS)-Induced Colitis |
| title_full_unstemmed | Human Umbilical Cord Mesenchymal Stem Cells Ameliorate Mice Trinitrobenzene Sulfonic Acid (TNBS)-Induced Colitis |
| title_short | Human Umbilical Cord Mesenchymal Stem Cells Ameliorate Mice Trinitrobenzene Sulfonic Acid (TNBS)-Induced Colitis |
| title_sort | human umbilical cord mesenchymal stem cells ameliorate mice trinitrobenzene sulfonic acid tnbs induced colitis |
| url | https://doi.org/10.3727/096368910X557245 |
| work_keys_str_mv | AT luliang humanumbilicalcordmesenchymalstemcellsamelioratemicetrinitrobenzenesulfonicacidtnbsinducedcolitis AT chunlandong humanumbilicalcordmesenchymalstemcellsamelioratemicetrinitrobenzenesulfonicacidtnbsinducedcolitis AT xiaojunchen humanumbilicalcordmesenchymalstemcellsamelioratemicetrinitrobenzenesulfonicacidtnbsinducedcolitis AT zhihongfang humanumbilicalcordmesenchymalstemcellsamelioratemicetrinitrobenzenesulfonicacidtnbsinducedcolitis AT jiexu humanumbilicalcordmesenchymalstemcellsamelioratemicetrinitrobenzenesulfonicacidtnbsinducedcolitis AT mengliu humanumbilicalcordmesenchymalstemcellsamelioratemicetrinitrobenzenesulfonicacidtnbsinducedcolitis AT xiaoguangzhang humanumbilicalcordmesenchymalstemcellsamelioratemicetrinitrobenzenesulfonicacidtnbsinducedcolitis AT dongshenggu humanumbilicalcordmesenchymalstemcellsamelioratemicetrinitrobenzenesulfonicacidtnbsinducedcolitis AT dingwang humanumbilicalcordmesenchymalstemcellsamelioratemicetrinitrobenzenesulfonicacidtnbsinducedcolitis AT weitingdu humanumbilicalcordmesenchymalstemcellsamelioratemicetrinitrobenzenesulfonicacidtnbsinducedcolitis AT delinzhuphd humanumbilicalcordmesenchymalstemcellsamelioratemicetrinitrobenzenesulfonicacidtnbsinducedcolitis AT zhongchaohanmdphd humanumbilicalcordmesenchymalstemcellsamelioratemicetrinitrobenzenesulfonicacidtnbsinducedcolitis |