Abstract
Background Embryonic metanephros is the mammalian renal anlagen, which is considered as a potential source for the regeneration of functional whole kidneys. Some studies reported that metanephros implanted into unilateral nephrectomized animals can develop into kidney tissue. However, kidneys are nephrotoxic in renal failure patients, and whether metanephros can grow in nephrotoxic has not been reported. This study aims to investigate the growth of metanephros in acute nephrotoxic environment and analyze the therapeutic effect of metanephros microenvironment on acute kidney injury (AKI). Methods AKI was induced in 200 g Wistar rats by giving intramuscular injections of 50% glycerol (10 mL/kg) in their hind limbs. 45 rats were divided randomly into three groups (control, glycerin, and metanephros). Metanephros group was transplanted two metanephroi (embryonic day 15) into the renal capsule of AKI rats. Glycerin group was AKI rats without transplantation. Control group was untreated. Results Mature glomeruli and tubules were detected in the grafts in metanephros group, which means that metanephroi can grow into tissues with mature kidney structure under acute nephrotoxic. Then, we assessed the renal function of host rats and found that there were fewer tubular necrosis in metanephros group than glycerin group, and the serum creatinine and urea nitrogen were significantly lower in metanephros group than glycerin group. Conclusion These results suggested that embryonic metanephroi can grow into tissues with mature kidney structure under acute nephrotoxic, and the graft microenvironment was effective in inhibiting the progression of AKI, which provides a new approach for the treatment of acute renal injury.
Highlights
The microenvironment derived from transplanted metanephros could maintain a blood pressure of the host animal and inhibit the progression of vascular calcification in rats with adenine-induced renal failure by producing renal hormones, including EPO and renin [12,13]. These results suggested that the microenvironment might be useful in the treatment of nephropathy; there have been no reports that whether the metanephros microenvironment is beneficial in the treatment of acute kidney injury (AKI)
The results showed that the levels of serum creatinine and urea nitrogen in AKI group were significantly higher than the control group (Figure 1(B)), which indicate that the renal function of the AKI group decreased sharply, and the animal model was made successfully
What’s more, we found that metanephroi microenvironment could effectively shorten the recovery time of AKI compared with the control rats
Summary
The complexity of the anatomical structure of the kidney makes it one of the most difficult challenges in the field of organ regeneration [1]. The embryonic metanephros is the mammalian renal anlagen, which is thought to develop into all cell types of adult kidney, and is considered as one of the potential sources for the regeneration of functional whole kidneys [2,3]. Metanephros group was transplanted two metanephroi (embryonic day 15) into the renal capsule of AKI rats. Results: Mature glomeruli and tubules were detected in the grafts in metanephros group, which means that metanephroi can grow into tissues with mature kidney structure under acute nephrotoxic. Conclusion: These results suggested that embryonic metanephroi can grow into tissues with mature kidney structure under acute nephrotoxic, and the graft microenvironment was effective in inhibiting the progression of AKI, which provides a new approach for the treatment of acute renal injury
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