Clinical Translation of Mesenchymal Stromal Cell Therapies in Nephrology

Abstract

Mesenchymal stromal cells have emerged as potential candidates for cell-based therapies to modulate the immune response in organ transplantation and repair tissues after acute or chronic injury. Preclinical studies have shown convincingly in rodent models that mesenchymal stromal cells can prolong solid organ graft survival and that they can induce immune tolerance, accelerate recovery from AKI, and promote functional improvement in chronic nephropathies. Multiple complex properties of the cells, including immunomodulatory, anti-inflammatory, and proregenerative effects, seem to contribute. The promising preclinical studies have encouraged investigators to explore the safety, tolerability, and efficacy of mesenchymal stromal cell-based therapy in pilot clinical trials, including those for bone marrow and solid organ transplantation, autoimmune diseases, and tissue and organ repair. Here, we review the available data on culture-expanded mesenchymal stromal cells tested in renal transplantation, AKI, and CKD. We also briefly discuss the relevant issues that must be addressed to ensure rigorous assessment of the safety and efficacy of mesenchymal stromal cell therapies to allow the translation of this research into the practice of clinical nephrology.

Keywords: acute kidney injury; kidney disease; mesenchymal stromal cells.

Figure 1.

MSCs exert their potential beneficial effects both systemically and at the renal level. MSCs, either constitutively or through crosstalk with target cells, release a multitude of cytokines, growth factors, and microvesicles that can inhibit the inflammatory functions of adaptive and innate immune cells and promote the development of regulatory cell populations, such as CD4⁺Foxp3⁺ Tregs, M2 macrophages, and myeloid-derived suppressor cells (MDSCs), with their own renoprotective effects. MSC secretome protects tubular cells from apoptosis and oxidative stress, favors angiogenesis, prevents/reverses renal fibrosis, inhibits inflammatory cell infiltration, and stimulates the endogenous process of renal repair. DC, dendritic cell; miRNA, micro RNA; Th, CD4⁺ T helper cell.