Stem cell replacement therapy for reflux nephropathy.
Reflux nephropathy is a condition in which the kidneys are damaged or scarred over time by the backward flow of urine into the kidney. This condition may cause kidney failure in both children and adults. The long-term goal of the 'Developing a stem cell based therapy to replace nephrons lost through reflux nephropathy ' (RENALSTEM) project was the development of stem cell based replacement therapy to prevent chronic kidney disease. During the initial stage (first 17 months) the major goal was to develop a non-invasive method to monitor stem cells following their transplantation. Magnetic nanoparticle (MNP) labelling of the cells coupled with magnetic resonance imaging (MRI) has the advantages over other imaging techniques because the magnetic signal does not diminish with tissue depth. However, most MNPs available to date are quickly degraded within the cellular environment. Researchers of the project prepared MNPs with a protective coating and demonstrated that these MNPs were more readily retained inside the stem cells than were commercial MNPs. RENALSTEM MNPs caused no significant cytotoxicity at concentrations of 30 micrograms per ml per 100 000 cells. Embryonic stem cells labelled with the MNPs expressed similar levels of the pluripotency markers and expressed markers of three germ layer derivatives. Stem cells labelled with the MNPs were able to undergo osteogenesis and adipogenesis to a similar extent as unlabelled stem cells. This demonstrates that the developed MNPs had no adverse effects on pluripotency and differentiation potential of stem cells. The results of this initial stage of the project formed the basis of a proposal to a United Kingdom stem sell initiative that was funded in March 2010. Two papers have been published in the journals of IEEE Transactions on Nanoscience (2010) and the Journal of Nanoscience and Nanotechnology (2011). Further investigation based on RENALSTEM results would be a significant step forward in the development of stem cell based therapies in general.