Stem/Stromal Cells for Treatment of Kidney Injuries With Focus on Preclinical Models

Abstract

Within the last years, the use of stem cells (embryonic, induced pluripotent stem cells, or hematopoietic stem cells), Progenitor cells (e.g., endothelial progenitor cells), and most intensely mesenchymal stromal cells (MSC) has emerged as a promising cell-based therapy for several diseases including nephropathy. For patients with end-stage renal disease (ESRD), dialysis or finally organ transplantation are the only therapeutic modalities available. Since ESRD is associated with a high healthcare expenditure, MSC therapy represents an innovative approach. In a variety of preclinical and clinical studies, MSC have shown to exert renoprotective properties, mediated mainly by paracrine effects, immunomodulation, regulation of inflammation, secretion of several trophic factors, and possibly differentiation to renal precursors. However, studies are highly diverse; thus, knowledge is still limited regarding the exact mode of action, source of MSC in comparison to other stem cell types, administration route and dose, tracking of cells and documentation of therapeutic efficacy by new imaging techniques and tissue visualization. The aim of this review is to provide a summary of published studies of stem cell therapy in acute and chronic kidney injury, diabetic nephropathy, polycystic kidney disease, and kidney transplantation. Preclinical studies with allogeneic or xenogeneic cell therapy were first addressed, followed by a summary of clinical trials carried out with autologous or allogeneic hMSC. Studies were analyzed with respect to source of cell type, mechanism of action etc.

Human amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injury

“…One hundred microliters of cell-free vehicle (PBS), hAECs (1 × 10 6 cells), or hAECs-EXO (about 3 × 10 8 exosomes) in vehicle was injected into injured mice intravenously at the end of the procedure. The dosage of hAECs (1 × 10 6 cells/mouse) in the treatment group was determined by the toxicity test and based on previous studies that used mesenchymal stem cells in murine IRI models [ 23 , 24 ]. For toxicity test of hAECs on C57BL/6 by intravenous injection, three dose escalations, 2.5 × 10 7 cells/kg, 5.0 × 10 7 cells/kg, and 1.0 × 10 8 cells/kg, were examined, respectively.…”

Organ Preservation into the 2020s: The Era of Dynamic Intervention

“…The therapeutic action of MSCs is associated with paracrine effects of secretomes, microvesicles, and exosomes, which are involved in the transfer of proteins and miRNA to neighboring cells. In total, MSCs secrete a lot of bioregulators such as IDO, TGF-α, TGF-β, prostaglandin E2, HGF, IL-6, IL-10, VEGF, and bFGF [99, 100]. These and other not yet identified bioregulators have diverse actions, such as modulating the local immune system, enhancing angiogenesis, preventing ROS production and cell apoptosis, as well as stimulating survival, proliferation, and differentiation of resident tissue cells [101].…”

Cell-derived Secretome for the Treatment of Renal Disease

“…Further studies are needed to characterize better and define the secreting factors, which allows for improved control and regulation for clinical translation. Furthermore, clinical efficacy and indication need to be assessed in welldesigned and controlled clinical trials 81) .…”