Secreted Factors from Bone Marrow Stromal Cells Upregulate IL-10 and Reverse Acute Kidney Injury
Author(s)
Milwid, John Miles; Ichimura, Takaharu; Li, Matthew; Jiao, Yunxin; Lee, Jungwoo; Yarmush, Joshua S.; Parekkadan, Biju; Tilles, Arno W.; Bonventre, Joseph V.; Yarmush, Martin L.; ... Show more Show less
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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.
Date issued
2012Department
Harvard University--MIT Division of Health Sciences and TechnologyJournal
Stem Cells International
Publisher
Hindawi Publishing Corporation
Citation
Milwid, Jack M. et al. "Secreted Factors from Bone Marrow Stromal Cells Upregulate IL-10 and Reverse Acute Kidney Injury." Stem Cells International, Volume 2012 (2012), Article ID 392050, 12 pages.
Version: Final published version
ISSN
1687-966X
1687-9678