Secreted Factors from Bone Marrow Stromal Cells Upregulate IL-10 and Reverse Acute Kidney Injury
Acute kidney injury is a devastating syndrome that afflicts over 2,000,000 people in the US per year, with an associated mortality of greater than 70% in severe cases. Unfortunately, standard-of-care treatments are not sufficient for modifying the course of disease. Many groups have explored the use...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2012/392050 |
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| author | Jack M. Milwid Takaharu Ichimura Matthew Li Yunxin Jiao Jungwoo Lee Joshua S. Yarmush Biju Parekkadan Arno W. Tilles Joseph V. Bonventre Martin L. Yarmush |
| author_facet | Jack M. Milwid Takaharu Ichimura Matthew Li Yunxin Jiao Jungwoo Lee Joshua S. Yarmush Biju Parekkadan Arno W. Tilles Joseph V. Bonventre Martin L. Yarmush |
| author_sort | Jack M. Milwid |
| collection | DOAJ |
| description | Acute kidney injury is a devastating syndrome that afflicts over 2,000,000 people in the US per year, with an associated mortality of greater than 70% in severe cases. Unfortunately, standard-of-care treatments are not sufficient for modifying the course of disease. Many groups have explored the use of bone marrow stromal cells (BMSCs) for the treatment of AKI because BMSCs have been shown to possess unique anti-inflammatory, cytoprotective, and regenerative properties in vitro and in vivo. It is yet unresolved whether the primary mechanisms controlling BMSC therapy in AKI depend on direct cell infusion, or whether BMSC-secreted factors alone are sufficient for mitigating the injury. Here we show that BMSC-secreted factors are capable of providing a survival benefit to rats subjected to cisplatin-induced AKI. We observed that when BMSC-conditioned medium (BMSC-CM) is administered intravenously, it prevents tubular apoptosis and necrosis and ameliorates AKI. In addition, we observed that BMSC-CM causes IL-10 upregulation in treated animals, which is important to animal survival and protection of the kidney. In all, these results demonstrate that BMSC-secreted factors are capable of providing support without cell transplantation, and the IL-10 increase seen in BMSC-CM-treated animals correlates with attenuation of severe AKI. |
| format | Article |
| id | doaj-art-d12e6a5fc8d849d3ad2965f2016f1535 |
| institution | OA Journals |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-d12e6a5fc8d849d3ad2965f2016f15352025-08-20T02:19:55ZengWileyStem Cells International1687-966X1687-96782012-01-01201210.1155/2012/392050392050Secreted Factors from Bone Marrow Stromal Cells Upregulate IL-10 and Reverse Acute Kidney InjuryJack M. Milwid0Takaharu Ichimura1Matthew Li2Yunxin Jiao3Jungwoo Lee4Joshua S. Yarmush5Biju Parekkadan6Arno W. Tilles7Joseph V. Bonventre8Martin L. Yarmush9Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School, 51 Blossom Street, Boston, MA 02114, USARenal Medicine Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USACenter for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School, 51 Blossom Street, Boston, MA 02114, USACenter for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School, 51 Blossom Street, Boston, MA 02114, USACenter for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School, 51 Blossom Street, Boston, MA 02114, USACenter for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School, 51 Blossom Street, Boston, MA 02114, USACenter for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School, 51 Blossom Street, Boston, MA 02114, USADepartment of Research and Development, Sentien Biotechnologies, Inc., Medford, MA 02155, USAHarvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USACenter for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School, 51 Blossom Street, Boston, MA 02114, USAAcute kidney injury is a devastating syndrome that afflicts over 2,000,000 people in the US per year, with an associated mortality of greater than 70% in severe cases. Unfortunately, standard-of-care treatments are not sufficient for modifying the course of disease. Many groups have explored the use of bone marrow stromal cells (BMSCs) for the treatment of AKI because BMSCs have been shown to possess unique anti-inflammatory, cytoprotective, and regenerative properties in vitro and in vivo. It is yet unresolved whether the primary mechanisms controlling BMSC therapy in AKI depend on direct cell infusion, or whether BMSC-secreted factors alone are sufficient for mitigating the injury. Here we show that BMSC-secreted factors are capable of providing a survival benefit to rats subjected to cisplatin-induced AKI. We observed that when BMSC-conditioned medium (BMSC-CM) is administered intravenously, it prevents tubular apoptosis and necrosis and ameliorates AKI. In addition, we observed that BMSC-CM causes IL-10 upregulation in treated animals, which is important to animal survival and protection of the kidney. In all, these results demonstrate that BMSC-secreted factors are capable of providing support without cell transplantation, and the IL-10 increase seen in BMSC-CM-treated animals correlates with attenuation of severe AKI.http://dx.doi.org/10.1155/2012/392050 |
| spellingShingle | Jack M. Milwid Takaharu Ichimura Matthew Li Yunxin Jiao Jungwoo Lee Joshua S. Yarmush Biju Parekkadan Arno W. Tilles Joseph V. Bonventre Martin L. Yarmush Secreted Factors from Bone Marrow Stromal Cells Upregulate IL-10 and Reverse Acute Kidney Injury Stem Cells International |
| title | Secreted Factors from Bone Marrow Stromal Cells Upregulate IL-10 and Reverse Acute Kidney Injury |
| title_full | Secreted Factors from Bone Marrow Stromal Cells Upregulate IL-10 and Reverse Acute Kidney Injury |
| title_fullStr | Secreted Factors from Bone Marrow Stromal Cells Upregulate IL-10 and Reverse Acute Kidney Injury |
| title_full_unstemmed | Secreted Factors from Bone Marrow Stromal Cells Upregulate IL-10 and Reverse Acute Kidney Injury |
| title_short | Secreted Factors from Bone Marrow Stromal Cells Upregulate IL-10 and Reverse Acute Kidney Injury |
| title_sort | secreted factors from bone marrow stromal cells upregulate il 10 and reverse acute kidney injury |
| url | http://dx.doi.org/10.1155/2012/392050 |
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