The alleviation of acute and chronic kidney injury by human Wharton's jelly-derived mesenchymal stromal cells triggered by ischemia-reperfusion injury via an endocrine mechanism |
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| Authors: | Tao Du Jun Cheng Liang Zhong Xin-Feng Zhao Jiang Zhu Ying-Jian Zhu Guo-Hua Liu |
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| Institution: | 1. Transplant Immunology Research Laboratory, Clinical Nephrology Unit, Department of Internal Medicine—DIMI, University of Genova, Genova, Italy;2. IRCCS Azienda Ospedaliera Universitaria San Martino—IST, Clinical Nephrology, Dialysis and Transplantation, Largo R. Benzi, 10-16132, Genova, Italy;3. Pediatric Nephrology and Transplantation, G. Gaslini Institute, Via Gaslini, 5-16147, Genova, Italy |
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| Abstract: | Background aimsThe effects of human Wharton's jelly-derived mesenchymal stromal cells (WJ-MSC) on acute and chronic kidney injury induced by ischemia-reperfusion injury (IRI) were assessed.MethodsWJ-MSC were injected intravenously immediately after solitary kidney ischemia for 45 min. Cells were labeled with 5-bromo-2′deoxy-uridine (BrdU) for tracing in vivo. At 48 h post-IRI, serum creatinine and blood urea nitrogen (BUN) were measured. Tubular cell proliferation and apoptosis as well as activation of the Akt signal were identified by immunostaining. Real-time polymerase chain reaction (PCR) was employed to determine gene expression of inflammation-related cytokines and hepatocyte growth factor (HGF). Levels of human HGF were assayed by enzyme-linked immunosorbant assay (ELISA). Twenty-two weeks later, renal fibrosis was assessed by Masson's tri-chrome staining, collagen content and α-smooth muscle actin (α-SMA) staining.ResultsThere was no sign of labeled cells residing in the damaged kidney. Acute renal dysfunction elicited by IRI was considerably improved by WJ-MSC, in parallel with a stronger proliferative response and less apoptotic events. Additionally, phosphoAkt staining in injured tubular cells was substantially intensified. Cell treatment also caused a remarkable up-regulation of kidney interleukin (IL)-10, heme oxygenase (HO)-1 and HGF expression. Human HGF was detected in cell supernatants and the serum of cell-infused rats. Moreover, IRI-initiated fibrosis was abrogated by cell therapy, coincident with function amelioration.ConclusionsWJ-MSC alleviate acute kidney injury, thereby rescuing the ensuing fibrotic lesions in an endocrine manner. The Akt signal in impaired tubular cells is reinforced by WJ-MSC, facilitating cell resistance to apoptosis and cell proliferation. HGF, either delivered or induced by WJ-MSC, is an important contributor. |
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