Stem Cell Therapies to Modulate Harmful Immune Responses in Kidney Disease: Progress Toward Clinical Validation

Stem cell therapies hold promise for halting or reversing kidney disease and improving kidney transplant (KTx) outcomes. One route to large-scale clinical application of stem cell therapies for kidney disease is through their capacity to modulate the balance between tissue injury and repair via crosstalk with other cells. Among the key disease-modulating effects of stem cells is their interaction with components of the immune system involved in harmful inflammation during acute kidney injury (AKI), chronic kidney disease (CKD) and complications of KTx. Extensive basic research demonstrates that stem cells employ diverse paracrine mechanisms to re-program immunological activities from pro-inflammatory/pro-fibrotic to anti-inflammatory/pro-repair. The therapeutic benefits of these effects are confirmed in many pre-clinical models of AKI, CKD and KTx for autologous and allogeneic stem cells including hematopoietic stem cells, mesenchymal stem cells, renal progenitor cells, and induced pluripotent stem cells. Nonetheless, translating these findings into therapeutic immunomodulatory cell products that improve the lives of those with kidney disease is highly challenging. The aims of this review are to: (a) Summarize recent insights into the common molecular and cellular mechanisms of immune-mediated tissue injury in kidney disease and KTx along with the types of stem therapies that have been developed to address them. (b) Critically evaluate the extent to which clinical trials of stem cell products have validated such effects in humans with kidney disease and KTx. (c) Identify key bottlenecks to the large-scale application of stem cell therapies to reduce the burden of kidney disease on patients and societies.