Experimental Evaluation of Kidney Regeneration by Organ Scaffold Recellularization

Andrea Remuzzi,Nadia Azzollini,Ariela Benigni,Barbara Bonandrini,Sara Silvani,Giuseppe Remuzzi,Roberta Nossa,Marina Figliuzzi

doi:10.1038/srep43502

Abstract

The rising number of patients needing renal replacement therapy, alongside the significant clinical and economic limitations of current therapies, creates an imperative need for new strategies to treat kidney diseases. Kidney bioengineering through the production of acellular scaffolds and recellularization with stem cells is one potential strategy. While protocols for obtaining organ scaffolds have been developed successfully, scaffold recellularization is more challenging. We evaluated the potential of in vivo and in vitro kidney scaffold recellularization procedures. Our results show that acellular scaffolds implanted in rats cannot be repopulated with host cells, and in vitro recellularization is necessary. However, we obtained very limited and inconsistent cell seeding when using different infusion protocols, regardless of injection site. We also obtained experimental and theoretical data indicating that uniform cell delivery into the kidney scaffolds cannot be obtained using these infusion protocols, due to the permeability of the extracellular matrix of the scaffold. Our results highlight the major physical barriers that limit in vitro recellularization of acellular kidney scaffolds and the obstacles that must be investigated to effectively advance this strategy for regenerative medicine.

Highlights

Rising global rates of chronic diseases, such as diabetes and hypertension, portend a consequent rise in end-stage renal disease (ESRD)[1]
The dynamic changes of implanted acellular scaffolds indicated that cellular repopulation does not occur in the scaffold vasculature and parenchyma over time, while the scaffold extracellular matrix (ECM) matrix starts to be degraded and reabsorbed
After the successful development of tissue engineering applications, from the laboratory to the clinic, it has been suggested that a similar approach could have great potential to create functional organs in the laboratory[19,29]

Summary

Introduction

Rising global rates of chronic diseases, such as diabetes and hypertension, portend a consequent rise in end-stage renal disease (ESRD)[1]. There are several recent reports in the literature of experimental methods being used to repopulate acellular kidney scaffolds Cell seeding within these scaffolds has been performed by perfusing cell suspensions through either the renal artery or the ureter[8,16,17]. To obtain cell engraftment in the renal tubules and in the collecting system, Song et al.[16] infused neonatal rat kidney cells through the ureter while a negative pressure gradient was applied to the organ chamber. Using this technique, some cells were distributed throughout the tubular compartment, up to the glomerular tuft. Caralt et al.[9] infused a higher number of human renal cortical tubular epithelial cells in rat kidney scaffolds at a higher pressure than is usually adopted, and obtained up to 50% coverage in some parts of the renal parenchyma 24 hours after seeding

Methods

Results

Conclusion