RenalToolBox · Developing novel tools and technologies to assess the safety and efficacy of cell-based regenerative medicine therapies, focusing on kidney disease

Developing novel tools and technologies to assess the safety and efficacy of cell-based regenerative medicine therapies, focusing on kidney disease

Chronic diseases are the leading cause of mortality, with chronic kidney disease (CKD) affecting >10% of the population worldwide. There is a need for therapies that can impact the survival and quality of life of CKD patients. Therapies based on mesenchymal stromal cells (MSCs) are showing promise in rodent models of kidney disease but before they can be used for CKD we need: (i) cost-effective and convenient methods for diagnosing CKD, (ii) reliable data on the safety and efficacy of MSC therapies and (iii) a better understanding of which MSCs have greatest therapeutic potential and how they might act to prevent kidney disease. Our three research objectives and conclusions were: 1. Develop novel tools for diagnosing kidney disease and assessing renal function: a new device to measure kidney function quickly and easily was devised. This was based on the excretion/absorption of tracers given intravenously, with the measurements obtained via a device attached to the skin. We also identified biomarkers that can indicate the health/disease state of the kidney, to monitor the progression and regression of renal disease more accurately. Finally, a kidney-on-a-chip device for the testing of tracers and MSC efficacy was developed. 2. Develop and apply cutting-edge imaging technologies to evaluate the safety and efficacy of MSCs in a rodent model of kidney disease: to assess safety, we applied complementary imaging technologies and probes to monitor the biodistribution and fate of MSCs in animals and, at study end-points, in tissues. For efficacy, we applied novel imaging strategies and analysis tools to monitor renal function and structure longitudinally in rodents with an ischaemia reperfusion injury (IRI). Intact organs were analysed post-mortem with novel microscopy ‘clearing’ techniques to validate the in vivo biodistribution results, accurately quantify the extent of morphological damage and determine potential mechanisms by which MSCs act. 3. Establish the optimal source of MSCs, develop a matrix of potency assays and explore therapeutic mechanisms: we compared the properties and therapeutic potential of MSCs derived from different tissues (bone marrow, adipose and umbilical cord) to identify differences in their potential to treat kidney injury. We also looked at the properties of extracellular vesicles (EVs), a product of MSC culture, and their therapeutic effects.

Data: CORDIS, © European Union