A new Bioengineering Solution to Kidney Disease

The number of premature deaths due to chronic kidney disease (CKD) reflects the inadequacy of the currently available drugs and the growing epidemic worldwide. These patients wait for a kidney transplant or receive renal replacement therapy in the form of dialysis. Cell-based gene therapy represents a promising treatment alternative for patients, and has gained increased momentum in the last decade.

Central to this excitement is the use of microRNA (miRNA) as a new target for drug discovery. However, the advancement of miRNA therapy for kidney disease patients is hampered by difficulties in delivering miRNAs to the damaged kidney in a robust and sustainable manner.
One way to overcome the challenge of miRNA delivery to damaged kidneys is by harnessing the regenerative potential of mesenchymal stem cells (MSCs). However, a major challenge is to support the survival of the MSCs once injected, where patients present with a harsh tissue environment due to long-term inflammation that culminates during the course of FSGS. The number of transplanted MSCs, and the survival of the cells at the site of tissue damage are critical for the efficacy of MSC therapies and these factors have hampered successful clinical trials.

In order to overcome this challenge, we have developed a novel bioengineering delivery system that consists of a long-lasting, biocompatible hydrogel to deliver MSC-derived miRNA to reverse the devastating effects of CKD. This hydrogel cell delivery system is innovative and has the potential to reduce chronic fibrosis and to significantly enhance the development of novel cell/drug-delivery systems for safe treatment of long-term complications.

The PhD project will provide an essential pre-clinical, proof-of-concept approach for translation to the clinic. The study will engineer human MSCs to overexpress a miRNA, that can be used to reduce fibrosis and to reverse established kidney damage. MSC encapsulation by the hydrogel that is injected subcutaneously, allows for sustained local release of miRNA that provides a physical barrier to protect the transplanted cells from hostile inflammatory microenvironments, resulting in prolonged cell survival and improved kidney function over the long term.