Multimodal Imaging Techniques Show Differences in Homing Capacity Between Mesenchymal Stromal Cells and Macrophages in Mouse Renal Injury Models

PURPOSE: The question of whether mesenchymal stromal cells (MSCs) home to injured kidneys remains a contested issue. To try and understand the basis for contradictory findings reported in the literature, our purpose here was to investigate whether MSC homing capacity is influenced by administration route, the type of injury model used, and/or the presence of exogenous macrophages. PROCEDURES: To assess the viability, whole-body biodistribution, and intra-renal biodistribution of MSCs, we used a multimodal imaging strategy comprising bioluminescence and magnetic resonance imaging. The effect of administration route (venous or arterial) on the ability of MSCs to home to injured renal tissue, and persist there, was assessed in a glomerular injury model (induced by the nephrotoxicant, Adriamycin) and a tubular injury model induced by ischaemia-reperfusion injury (IRI). Exogenous macrophages were used as a positive control because these cells are known to home to injured mouse kidneys. To assess whether the homing capacity of MSCs can be influenced by the presence of exogenous macrophages, we used a dual-bioluminescence strategy that allowed the whole-body biodistribution of the two cell types to be monitored simultaneously in individual animals. RESULTS: Following intravenous administration, no MSCs were detected in the kidneys, irrespective of whether the mice had been subjected to renal injury. After arterial administration via the left cardiac ventricle, MSCs transiently populated the kidneys, but no preferential homing or persistence was observed in injured renal tissue after unilateral IRI. An exception was when MSCs were co-administered with exogenous macrophages; here, we observed some homing of MSCs to the injured kidney. CONCLUSIONS: Our findings strongly suggest that MSCs do not home to injured kidneys. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11307-019-01458-8) contains supplementary material, which is available to authorized users.