Abstract
BackgroundEndometrial regenerative cells (ERCs) is an attractive novel type of adult mesenchymal stem cells that can be non-invasively obtained from menstrual blood and are easily replicated at a large scale without tumorigenesis. We have previously reported that ERCs exhibit unique immunoregulatory properties in experimental studies in vitro and in vivo. In this study, the protective effects of ERCs on renal ischemia–reperfusion injury (IRI) were examined.MethodsRenal IRI in C57BL/6 mice was induced by clipping bilateral renal pedicles for 30 min, followed by reperfusion for 48 h. ERCs were isolated from healthy female menstrual blood, and were injected (1 million/mouse, i.v.) into mice 2 h prior to IRI induction. Renal function, pathological and immunohistological changes, cell populations and cytokine profiles were evaluated after 48 h of renal reperfusion.ResultsHere, we showed that as compared to untreated controls, administration of ERCs effectively prevented renal damage after IRI, indicated by better renal function and less pathological changes, which were associated with increased serum levels of IL-4, but decreased levels of TNF-α, IFN-γ and IL-6. Also, ERC-treated mice displayed significantly less splenic and renal CD4+ and CD8+ T cell populations, while the percentage of splenic CD4+CD25+ regulatory T cells and infiltrating M2 macrophages in the kidneys were significantly increased in ERC-treated mice.ConclusionsThis study demonstrates that the novel anti-inflammatory and immunoregulatory effects of ERCs are associated with attenuation of renal IRI, suggesting that the unique features of ERCs may make them a promising candidate for cell therapies in the treatment of ischemic acute kidney injury in patients.
Highlights
Endometrial regenerative cells (ERCs) is an attractive novel type of adult mesenchymal stem cells that can be non-invasively obtained from menstrual blood and are replicated at a large scale without tumorigenesis
This study demonstrates that the novel anti-inflammatory and immunoregulatory effects of ERCs are associated with attenuation of renal ischemia–reperfusion injury (IRI), suggesting that the unique features of ERCs may make them a promising candidate for cell therapies in the treatment of ischemic acute kidney injury in patients
We found that blood urea nitrogen (BUN) (Fig. 1a) and Cr (Fig. 1b) levels were markedly reduced by ERC treatment compared with those of untreated mice after IRI (p < 0.05), the levels of BUN and Cr were slightly higher than those of mice in sham control group (p < 0.05)
Summary
Endometrial regenerative cells (ERCs) is an attractive novel type of adult mesenchymal stem cells that can be non-invasively obtained from menstrual blood and are replicated at a large scale without tumorigenesis. The protective effects of ERCs on renal ischemia–reperfusion injury (IRI) were examined. The pathophysiology of renal IRI includes initial cellular damage caused by ischemia, as well as delayed renal injury resulting from inflammatory and immune responses following reperfusion [2]. Numerous studies have demonstrated that renal IRI is an inflammatory disease, which is mediated by innate and adoptive immune responses [3,4,5,6]. The activation and infiltration of neutrophils [5, 7], macrophages [8], T lymphocytes [9], monocytes and inflammatory mediators are involved in modulating severity of injury in experimental models of renal IRI [10,11,12,13]. Animal models have showed that inflammation begins as early as 30 min of reperfusion, and inhibition of the immune response
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