Mesenchymal stromal cell–based therapies for acute kidney injury: progress in the last decade

A little over 10 years ago, the therapeutic potential of mesenchymal stromal cells (MSCs) for the treatment of acute kidney injury (AKI) was becoming widely recognized. Since then, there has been further intensive study of this topic with a clear translational intent. Over the past decade, many more animal model studies have strengthened the evidence that systemically or locally delivered MSCs ameliorate renal injury in sterile and sepsis-associated AKI. Some of these preclinical studies have also provided a range of compelling new insights into the in vivo fate and mechanisms of action of MSCs in the setting of AKI and other inflammatory conditions. Coupled with increased knowledge of the functional roles of resident and infiltrating immune cell mediators in determining the severity and outcome of AKI, the progress made in the past decade would appear to have significantly strengthened the translational pathway for MSC-based therapies. In contrast, however, the extent of the clinical experience with MSC administration in human subjects with AKI or sepsis-associated AKI has been limited to a small number of early-phase clinical trials, which appear to demonstrate safety but have not thus far delivered a strong signal of efficacy. In this review, we summarize the most significant new developments in the field of MSC-based therapies as they relate to AKI and reflect on the key gaps in knowledge and technology that remain to be addressed for the true clinical potential of MSCs and, perhaps, other emerging cellular therapies to be realized.