Abstract
Background aims. The 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. Methods. WJ-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. Results. There 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. Conclusions. WJ-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.
Acknowledgements
We also thank Dr Yilin Cao, Dr Wei Liu and Dr Guangdong Zhou (Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China) and the National Tissue Engineering Center of China (Shanghai, PR China) for technical assistance.
Disclosure statement: The authors have no financial conflict of interest.
This study is supported by grants from the Research Program of Science and Technology Commission of Shanghai Municipality (10411967200) and Shanghai Song-Jiang Health Bureau (2011PD06) and National Natural Science Foundation of China (81170642) and Shanghai Shen Kang Plat-form Grant (SHDC12007206).