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Secreted factors from bone marrow stromal cells upregulate IL-10 and reverse acute kidney injury.

Milwid JM, Ichimura T, Li M, Jiao Y, Lee J, Yarmush JS, Parekkadan B, Tilles AW, Bonventre JV, Yarmush ML - Stem Cells Int (2012)

Bottom Line: Unfortunately, standard-of-care treatments are not sufficient for modifying the course of disease.Here we show that BMSC-secreted factors are capable of providing a survival benefit to rats subjected to cisplatin-induced AKI.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.

View Article: PubMed Central - PubMed

Affiliation: Center 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.

No MeSH data available.


Related in: MedlinePlus

BMSC-CM protects the native architecture of the kidney during AKI. Hematoxylin and eosin staining of sections of kidneys from rats administered a lethal dose of cisplatin (7.5 mg/kg) and sacrificed at 5 days following cisplatin administration. The rats were treated at 3, 9, 24, 48, and 72 hours following cisplatin administration, with 1 mL of either physiological saline (n = 4), or BMSC-conditioned medium (n = 3) i.v. Scale bar = 200 μm.
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fig3: BMSC-CM protects the native architecture of the kidney during AKI. Hematoxylin and eosin staining of sections of kidneys from rats administered a lethal dose of cisplatin (7.5 mg/kg) and sacrificed at 5 days following cisplatin administration. The rats were treated at 3, 9, 24, 48, and 72 hours following cisplatin administration, with 1 mL of either physiological saline (n = 4), or BMSC-conditioned medium (n = 3) i.v. Scale bar = 200 μm.

Mentions: From the results of the renal function markers, BUN and creatinine, it seemed likely that the BMSC-CM treatment was protecting the architecture of the kidney, thereby preserving GFR. When the rats were subjected to a lethal dose of cisplatin and then treated with saline (n = 4), H&E staining of the kidneys revealed cortical damage in the form of collapsed Bowman's capsule and proximal tubular necrosis, and outer medullary damage in the form of extensive tubular necrosis, deposition of debris and tubule casts, all consistent with cisplatin-mediated AKI (Figure 3). The injury was so severe that upon excision, the kidneys were grossly hemorrhagic and the normal tissue firmness was replaced with softness. The kidneys of the rats administered BMSC-CM (n = 3), on the other hand, sustained significantly less injury. H&E analysis revealed less tubular necrosis, diminished loss of brush borders, decreased denuding of tubular epithelium, and a reduction in apparent casts or accumulated debris.


Secreted factors from bone marrow stromal cells upregulate IL-10 and reverse acute kidney injury.

Milwid JM, Ichimura T, Li M, Jiao Y, Lee J, Yarmush JS, Parekkadan B, Tilles AW, Bonventre JV, Yarmush ML - Stem Cells Int (2012)

BMSC-CM protects the native architecture of the kidney during AKI. Hematoxylin and eosin staining of sections of kidneys from rats administered a lethal dose of cisplatin (7.5 mg/kg) and sacrificed at 5 days following cisplatin administration. The rats were treated at 3, 9, 24, 48, and 72 hours following cisplatin administration, with 1 mL of either physiological saline (n = 4), or BMSC-conditioned medium (n = 3) i.v. Scale bar = 200 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539665&req=5

fig3: BMSC-CM protects the native architecture of the kidney during AKI. Hematoxylin and eosin staining of sections of kidneys from rats administered a lethal dose of cisplatin (7.5 mg/kg) and sacrificed at 5 days following cisplatin administration. The rats were treated at 3, 9, 24, 48, and 72 hours following cisplatin administration, with 1 mL of either physiological saline (n = 4), or BMSC-conditioned medium (n = 3) i.v. Scale bar = 200 μm.
Mentions: From the results of the renal function markers, BUN and creatinine, it seemed likely that the BMSC-CM treatment was protecting the architecture of the kidney, thereby preserving GFR. When the rats were subjected to a lethal dose of cisplatin and then treated with saline (n = 4), H&E staining of the kidneys revealed cortical damage in the form of collapsed Bowman's capsule and proximal tubular necrosis, and outer medullary damage in the form of extensive tubular necrosis, deposition of debris and tubule casts, all consistent with cisplatin-mediated AKI (Figure 3). The injury was so severe that upon excision, the kidneys were grossly hemorrhagic and the normal tissue firmness was replaced with softness. The kidneys of the rats administered BMSC-CM (n = 3), on the other hand, sustained significantly less injury. H&E analysis revealed less tubular necrosis, diminished loss of brush borders, decreased denuding of tubular epithelium, and a reduction in apparent casts or accumulated debris.

Bottom Line: Unfortunately, standard-of-care treatments are not sufficient for modifying the course of disease.Here we show that BMSC-secreted factors are capable of providing a survival benefit to rats subjected to cisplatin-induced AKI.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.

View Article: PubMed Central - PubMed

Affiliation: Center 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.

No MeSH data available.


Related in: MedlinePlus