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Secreted factors from bone marrow stromal cells upregulate IL-10 and reverse acute kidney injury
Jack M Milwid1, Takaharu Ichimura, Matthew Li
1Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School, 51 Blossom Street, Boston, MA 02114, USA ; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Abstract:
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.
Insights
Bone marrow stromal cell (BMSC) factors, not cells, can treat acute kidney injury (AKI). BMSC-conditioned medium prevents kidney cell death and promotes survival by upregulating IL-10.
Area of Science:
- Nephrology
- Stem Cell Therapy
- Regenerative Medicine
Background:
- Acute kidney injury (AKI) affects over 2 million people annually in the US, with high mortality.
- Current treatments for AKI are insufficient to alter disease progression.
- Bone marrow stromal cells (BMSCs) show promise for AKI treatment due to anti-inflammatory and regenerative properties.
Purpose of the Study:
- To investigate if bone marrow stromal cell (BMSC)-secreted factors alone can mitigate cisplatin-induced AKI.
- To determine the therapeutic potential of BMSC-conditioned medium (BMSC-CM) in AKI treatment.
- To explore the role of IL-10 in BMSC-mediated protection against AKI.
Main Methods:
- Rats with cisplatin-induced AKI were treated with intravenous BMSC-CM.
- Tubular apoptosis and necrosis were assessed in kidney tissues.
- IL-10 levels in treated animals were measured to evaluate its correlation with kidney protection.
Main Results:
- Intravenous administration of BMSC-CM significantly ameliorated AKI in rats.
- BMSC-CM prevented tubular apoptosis and necrosis.
- BMSC-CM treatment led to IL-10 upregulation, which correlated with improved survival and kidney protection.
Conclusions:
- BMSC-secreted factors are sufficient for therapeutic benefit in AKI, without requiring cell transplantation.
- BMSC-CM offers a cell-free therapeutic strategy for AKI.
- IL-10 plays a crucial role in the protective effects of BMSC-CM against AKI.
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