Metanephros Transplantation Inhibits the Progression of Vascular Calcification in Rats with Adenine-Induced Renal Failure

Abstract

Background/Aim: Recent research has shown that transplanted metanephroi form primitive vascularized kidneys with histologically recognizable renal features. The aim of the present study was to determine the metabolic function of transplanted metanephroi in rats with chronic renal failure (CRF), with particular reference to secondary hyperparathyroidism and vascular calcification. Methods: CRF was induced in 11-week-old male Wistar rats by maintaining them on a 0.75% adenine diet for 4 weeks, followed by normal diet for an additional 2 weeks. At the end of adenine loading, whole metanephroi from embryonic day 15 rats were transplanted into the omentum and epididymis of the transplantation group. Vascular calcification was evaluated 2 weeks after metanephroi transplantation. Results: Metanephros transplantation significantly reduced vascular calcium and phosphorus content and suppressed the progression of vascular calcification as indicated by von Kossa staining of the media of the thoracic aorta. However, no significant differences between the adenine-fed control and transplantation groups were found regarding the serum levels of 1,25(OH)₂D₃, calcium or phosphorus or the calcium × phosphorus product. Conclusion: The present study has shown that transplantation of metanephroi suppresses the progression of vascular calcification via a mechanism that is independent of calcium-phosphorus dynamics.

Functional Human Podocytes Generated in Organoids from Amniotic Fluid Stem Cells

“…Previous studies have shown that renal primordial tissues continue to develop in vivo, become vascularized, and exhibit functional properties in neonatal 21 or adult 22,23 recipients. Similar approaches in recipients with different diseases have shown that embryonic kidneys can initiate regenerative processes in damaged kidney tissue, 24 regulate arterial blood pressure, 25 exhibit metabolic properties 26 and prolong life in anephric rats. 27,28 Although these methods showed promising therapeutic potential, they cannot be applied in experiments that seek to grow chimeric organs in vivo for testing the ability of stem cells to contribute to different structures in the organ and modeling human development or disease.…”

Microenvironment derived from metanephros transplantation inhibits the progression of acute kidney injury in glycerol-induced rat models

“…The embryonic metanephros, with less immunogenic, is a promising potential source for the generation of a functional whole kidney [25]. However, it has been reported that renal proximal tubular cell regeneration is inhibited in a nephrotoxic environment [12,13,[26][27][28]. Consequently, whether embryonic metanephros can grow and differentiate in nephrotoxic environment determines its application prospects in the treatment of nephropathy.…”

“…Moreover, because the metanephroi microenvironment grows under the renal capsule, its protective effect on the kidney is more targeted. Previous studies have determined that metanephroi microenvironment plays an important role in renal regeneration [10,38,39], prevention of vascular calcification [12], maintenance of blood pressure [13], and so on.…”

“…It is reported that the microenvironment derived from transplanted metanephros can induce the differentiation of exogenous stem cells into renal cells [11]. 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; however, there have been no reports that whether the metanephros microenvironment is beneficial in the treatment of AKI.…”

Reforming the Kidney Starting from a Single-Cell Suspension

“…The average levels of urea nitrogen and creatinine were higher in the cyst fluid that arose from the transplanted tissue than in the sera of the transplanted mice [4]. This also showed that metanephros transplantation can maintain the blood pressure in anephric rats with induced acute hypotension [14] and reduce vascular calcification in rats with chronic renal failure [15], suggesting that transplanted metanephroi have multiple renal functions other than urine production. Although the omentum is used mainly because a tight renal capsule does not confine it, and the host's vessels can be preferentially integrated into the transplant, the low hydrostatic pressure in the omentum may affect the acquisition of some renal function in the developed metanephros.…”