Mesenchymal Stem Cell‐Based Therapy for Kidney Disease: A Review of Clinical Evidence

Abstract

Mesenchymal stem cells form a population of self-renewing, multipotent cells that can be isolated from several tissues. Multiple preclinical studies have demonstrated that the administration of exogenous MSC could prevent renal injury and could promote renal recovery through a series of complex mechanisms, in particular via immunomodulation of the immune system and release of paracrine factors and microvesicles. Due to their therapeutic potentials, MSC are being evaluated as a possible player in treatment of human kidney disease, and an increasing number of clinical trials to assess the safety, feasibility, and efficacy of MSC-based therapy in various kidney diseases have been proposed. In the present review, we will summarize the current knowledge on MSC infusion to treat acute kidney injury, chronic kidney disease, diabetic nephropathy, focal segmental glomerulosclerosis, systemic lupus erythematosus, and kidney transplantation. The data obtained from these clinical trials will provide further insight into safety, feasibility, and efficacy of MSC-based therapy in renal pathologies and allow the design of consensus protocol for clinical purpose.

Cell-Based Therapies in Acute Kidney Injury (AKI)

“…Additional studies revealed the subcellular mechanisms of MSC-mediated tissue-protection to be predominantly indirect in nature. Firstly, the cells have been shown to secrete a heterogenous amount of paracrinic substances [28]. Secondly, they produce and excrete or shed extracellular vesicules [29].…”

“…Among the substances secreted by MSCs are monocyte chemoattractant protein-1 (MCP-1/CCL2), IL-6, IL-8, fibronectin, periostin, collagen, and metalloproteinase inhibitors. In addition, the cells produce growth factors such as insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) [28]. Microvesicles are small organelles in the size of 50-200 nm, released by shedding from biologically active cells.…”

“…Nevertheless, MSCs have meanwhile been employed in numerous clinical trials. As reported by Peired and colleagues [28], several clinical investigations have been initiated in subjects with kidney diseases. Lately, Dellepiane summarized trials currently performed in individuals at higher AKI risk [10].…”

Extracellular vesicles as regulators of tumor fate: crosstalk among cancer stem cells, tumor cells and mesenchymal stem cells

“…MSCs present self-renewal ability and multilineage differentiation into chondrocytes, osteocytes and adipocytes (mesoderm) and also into cells of ectodermic or endodermic origin (76). They have been widely investigated owing to their therapeutic potential in tissue injury or degenerative diseases, which is achieved through immunomodulatory regulation, angiogenesis, cell death inhibition, stimulation of proliferation and tropism from their niches (77)(78)(79). An important characteristic of these cells in supporting tissue recovery and regeneration is their chemotactic property, which accounts for their recruitment in response to injury and inflammation, with a tropism directed to injured sites.…”

Reading First Coordinates from the Nephrogenic Zone in Human Fetal Kidney

“…Nevertheless, clinical experiences in past years demonstrate that some regeneration is possible [2]. Because of which, substantial efforts are being made to stimulate regeneration with the help of implanted stem cells [3-6]. To provide an effective source and an optimal course of regeneration, different kinds of stem cells were tested and various implantation techniques tried [7, 8].…”