Mesenchymal stem cells prevent the rejection of fully allogenic islet grafts by the immunosuppressive activity of matrix metalloproteinase-2 and -9.
<p><strong>OBJECTIVE</strong> Mesenchymal stem cells (MSCs) are known to be capable of suppressing immune responses, but the molecular mechanisms involved and the therapeutic potential of MSCs remain to be clarified.</p> <p><strong>RESEARCH DESIGN AND METHODS</...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Diabetes Association
2009
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| _version_ | 1826272376010047488 |
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| author | Ding, Y Xu, D Feng, G Bushell, A Muschel, R Wood, K |
| author_facet | Ding, Y Xu, D Feng, G Bushell, A Muschel, R Wood, K |
| author_sort | Ding, Y |
| collection | OXFORD |
| description | <p><strong>OBJECTIVE</strong> Mesenchymal stem cells (MSCs) are known to be capable of suppressing immune responses, but the molecular mechanisms involved and the therapeutic potential of MSCs remain to be clarified.</p> <p><strong>RESEARCH DESIGN AND METHODS</strong> We investigated the molecular mechanisms underlying the immunosuppressive effects of MSCs in vitro and in vivo.</p> <p><strong>RESULTS</strong> Our results demonstrate that matrix metalloproteinases (MMPs) secreted by MSCs, in particular MMP-2 and MMP-9, play an important role in the suppressive activity of MSCs by reducing surface expression of CD25 on responding T-cells. Blocking the activity of MMP-2 and MMP-9 in vitro completely abolished the suppression of T-cell proliferation by MSCs and restored T-cell expression of CD25 as well as responsiveness to interleukin-2. In vivo, administration of MSCs significantly reduced delayed-type hypersensitivity responses to allogeneic antigen and profoundly prolonged the survival of fully allogeneic islet grafts in transplant recipients. Significantly, these MSC-mediated protective effects were completely reversed by in vivo inhibition of MMP-2 and MMP-9.</p> <p><strong>CONCLUSIONS</strong> We demonstrate that MSCs can prevent islet allograft rejection leading to stable, long-term normoglycemia. In addition, we provide a novel insight into the mechanism underlying the suppressive effects of MSCs on T-cell responses to alloantigen.</p> |
| first_indexed | 2024-03-06T22:11:35Z |
| format | Journal article |
| id | oxford-uuid:51fccbdf-09cc-4c63-b702-f9f491599995 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:11:35Z |
| publishDate | 2009 |
| publisher | American Diabetes Association |
| record_format | dspace |
| spelling | oxford-uuid:51fccbdf-09cc-4c63-b702-f9f4915999952022-03-26T16:22:57ZMesenchymal stem cells prevent the rejection of fully allogenic islet grafts by the immunosuppressive activity of matrix metalloproteinase-2 and -9.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:51fccbdf-09cc-4c63-b702-f9f491599995EnglishSymplectic Elements at OxfordAmerican Diabetes Association2009Ding, YXu, DFeng, GBushell, AMuschel, RWood, K<p><strong>OBJECTIVE</strong> Mesenchymal stem cells (MSCs) are known to be capable of suppressing immune responses, but the molecular mechanisms involved and the therapeutic potential of MSCs remain to be clarified.</p> <p><strong>RESEARCH DESIGN AND METHODS</strong> We investigated the molecular mechanisms underlying the immunosuppressive effects of MSCs in vitro and in vivo.</p> <p><strong>RESULTS</strong> Our results demonstrate that matrix metalloproteinases (MMPs) secreted by MSCs, in particular MMP-2 and MMP-9, play an important role in the suppressive activity of MSCs by reducing surface expression of CD25 on responding T-cells. Blocking the activity of MMP-2 and MMP-9 in vitro completely abolished the suppression of T-cell proliferation by MSCs and restored T-cell expression of CD25 as well as responsiveness to interleukin-2. In vivo, administration of MSCs significantly reduced delayed-type hypersensitivity responses to allogeneic antigen and profoundly prolonged the survival of fully allogeneic islet grafts in transplant recipients. Significantly, these MSC-mediated protective effects were completely reversed by in vivo inhibition of MMP-2 and MMP-9.</p> <p><strong>CONCLUSIONS</strong> We demonstrate that MSCs can prevent islet allograft rejection leading to stable, long-term normoglycemia. In addition, we provide a novel insight into the mechanism underlying the suppressive effects of MSCs on T-cell responses to alloantigen.</p> |
| spellingShingle | Ding, Y Xu, D Feng, G Bushell, A Muschel, R Wood, K Mesenchymal stem cells prevent the rejection of fully allogenic islet grafts by the immunosuppressive activity of matrix metalloproteinase-2 and -9. |
| title | Mesenchymal stem cells prevent the rejection of fully allogenic islet grafts by the immunosuppressive activity of matrix metalloproteinase-2 and -9. |
| title_full | Mesenchymal stem cells prevent the rejection of fully allogenic islet grafts by the immunosuppressive activity of matrix metalloproteinase-2 and -9. |
| title_fullStr | Mesenchymal stem cells prevent the rejection of fully allogenic islet grafts by the immunosuppressive activity of matrix metalloproteinase-2 and -9. |
| title_full_unstemmed | Mesenchymal stem cells prevent the rejection of fully allogenic islet grafts by the immunosuppressive activity of matrix metalloproteinase-2 and -9. |
| title_short | Mesenchymal stem cells prevent the rejection of fully allogenic islet grafts by the immunosuppressive activity of matrix metalloproteinase-2 and -9. |
| title_sort | mesenchymal stem cells prevent the rejection of fully allogenic islet grafts by the immunosuppressive activity of matrix metalloproteinase 2 and 9 |
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