In vivo regeneration of renal vessels post whole decellularized kidneys transplantation.

Jianse Zhang,Tinggang Chu,Kezhi Lin,Miaozhong Li,Lizhi Wu,Yaling Yu,Maolin Tang,Xinfa Lou,Yingkuan Shao,Zhibin Wang,Ali Alkhawaji,Jin Mei,Lina Zhao,Shixin Chen,Ting Li

doi:10.18632/oncotarget.6321

Abstract

Nearly 50 million patients in China live with end-stage renal disease (ESRD), and only about 4000 patients may receive kidney transplantation. The purpose of this study was to investigate regeneration of renal vessels post whole decellularized kidneys transplantation in vivo. We decellularized kidneys of donor rats by perfusing a detergent through the abdominal aorta, yielding feasible extracellular matrix, confirmed for acellularity before transplantation. Based on the concept of using the body as a bioreactor, we orthotopically transplanted the kidney and ureter scaffolds in recipient rats, and found the regeneration of vessels including artery and vein in the renal sinus following a spontaneous recanalization. Although the findings only represent an initial step toward the ultimate goal of the generation of fully functional kidneys in vivo, these findings suggest that the body itself, as the bioreactor, is a viable strategy for kidney regeneration.

Highlights

Chronic kidney disease (CKD) is a global health issue
Microscopic examination of hematoxylin and eosin (H&E) stained decellularized kidney specimens revealed that the integrity of the glomerular capsule, tubules and vessels was intact and cells were all removed compared with the native (Figure 2C-2H)
Transmission electron microscopy (TEM) assay showed that the decellularized kiney scaffolds were clear of any cellular/nuclear material compared with the native kidney, but the basement membrane extracellular matrix of the renal glomeruli, the renal tubules were kept intact (Figure 2I-2N),suggesting the potential to support regenerative ability

Summary

Introduction

Chronic kidney disease (CKD) is a global health issue. 120 million patients live with CKD in China alone [1]. Dialysis partially replaces the filtration properties of the kidney, but does not address the loss of homeostatic and endocrine functions [2,3,4]. Alternative to dialysis, which could holistically restore homeostatic renal functions, is kidney transplantation. Less than one percent of ESRD patients in China may receive kidney transplantation [1], lifelong immunosuppression is required to reduces the risk of chronic rejection [5, 6]. A potential solution to address these challenges is the application of organ engineering, which could be used to develop functional organ replacements in a timely manner

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