Challenges and opportunities for stem cell therapy in patients with chronic kidney disease

Abstract

Chronic kidney disease (CKD) is a global healthcare burden affecting billions of individuals worldwide. The kidney has limited regenerative capacity from chronic insults, and for the most common causes of CKD, no effective treatment exists to prevent progression to end-stage kidney failure. Therefore, novel interventions, such as regenerative cell-based therapies, need to be developed for CKD. Given the risk of allosensitization, autologous transplantation of cells to boost regenerative potential is preferred. Therefore, verification of cell function and vitality in CKD patients is imperative. Two cell types have been most commonly applied in regenerative medicine. Endothelial progenitor cells contribute to neovasculogenesis primarily through paracrine angiogenic activity and partly by differentiation into mature endothelial cells in situ. Mesenchymal stem cells also exert paracrine effects, including pro-angiogenic, anti-inflammatory, and anti-fibrotic activity. However, in CKD, multiple factors may contribute to reduced cell function, including older age, coexisting cardiovascular disease, diabetes, chronic inflammatory states, and uremia, which may limit the effectiveness of an autologous cell-based therapy approach. This review highlights current knowledge on stem and progenitor cell function and vitality, aspects of the uremic milieu that may serve as a barrier to therapy, and novel methods to improve stem cell function for potential transplantation.

Macrophage in chronic kidney disease

“…Therefore, interventions such as gene and cell-based therapies are being extensively developed as an alternative treatment modality for the prevention of progression to end-stage renal failure [68]. Nevertheless, there are very few therapies that induce renal repair in chronic nephropathies [69].…”

Allogeneic Mesenchymal Precursor Cells (MPC) in Diabetic Nephropathy: A Randomized, Placebo-controlled, Dose Escalation Study

“…The anti-inflammatory properties of adult, bone-marrow derived mesenchymal lineage cells may have beneficial effects in diabetic nephropathy, as suggested by observed effects on renal function and histology in animal models of chronic kidney disease (Prockop and Oh, 2012, Singer and Caplan, 2011, Cantaluppi et al, 2013). Other properties such as tropism for damaged tissues and secretion of a broad range of bioactive molecules with subsequent paracrine effects contribute to the effects on renal function and histopathology in preclinical chronic and acute kidney injury models (Papazova et al, 2015, Meirelles Lda et al, 2009, Hickson et al, 2016). In addition, the capacity of this cell type to reprogram macrophages from a proinflammatory M1 phenotype to the alternatively activated or anti-inflammatory M2 phenotype may also promote tissue repair (Maggini et al, 2010, Kim and Hematti, 2009).…”

Mechanistic Insight and Management of Diabetic Nephropathy: Recent Progress and Future Perspective

“…Apoptosis of stem cells is likely to promote eventual manifestation of kidney failure in diabetes mellitus [66]. Furthermore, the present study shows reductions in subsets of stem cells in peripheral blood and renal cell preparations of db/db mice which is a model of DN, which indicates that the decrease of stem cells might be a hallmark of DN [66, 67]. MSC transplantation is a promising therapeutic strategy to delay DN progression in animal models; however, the clinical trials should be performed to investigate the safety and efficacy of MSC transplantation in patients with DN [68].…”