Cell-based therapies for experimental chronic kidney disease: a systematic review and meta-analysis

Abstract

Cell-based therapy is a promising strategy for treating chronic kidney disease (CKD) and is currently the focus of preclinical studies. We performed a systematic review and meta-analysis to evaluate the efficacy of cell-based therapy in preclinical (animal) studies of CKD, and determined factors affecting cell-based therapy efficacy in order to guide future clinical trials. In total, 71 articles met the inclusion criteria. Standardised mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcome parameters including plasma urea, plasma creatinine, urinary protein, blood pressure, glomerular filtration rate, glomerulosclerosis and interstitial fibrosis. Sub-analysis for each outcome measure was performed for model-related factors (species, gender, model and timing of therapy) and cell-related factors (cell type, condition and origin, administration route and regime of therapy). Overall, meta-analysis showed that cell-based therapy reduced the development and progression of CKD. This was most prominent for urinary protein (SMD, 1.34; 95% CI, 1.00–1.68) and urea (1.09; 0.66–1.51), both P<0.001. Changes in plasma urea were associated with changes in both glomerulosclerosis and interstitial fibrosis. Sub-analysis showed that cell type (bone-marrow-derived progenitors and mesenchymal stromal cells being most effective) and administration route (intravenous or renal artery injection) were significant predictors of therapeutic efficacy. The timing of therapy in relation to clinical manifestation of disease, and cell origin and dose, were not associated with efficacy. Our meta-analysis confirms that cell-based therapies improve impaired renal function and morphology in preclinical models of CKD. Our analyses can be used to optimise experimental interventions and thus support both improved preclinical research and development of cell-based therapeutic interventions in a clinical setting.

Recent Progress in Stem Cell Therapy for Diabetic Nephropathy

“…Chronic diabetic kidney disease is characterized by a reduced renal regenerative capacity [13] , which is modulated by inflammation [14] . The link between inflammation and regeneration is the sharing of signaling pathways that regulate cell death cell cycle control.…”

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

“…However, direct evidence from glomerulosclerosis and interstitial fibrosis analyses was incomplete. Additionally, Li et al 24 found that human MSCs prevented hyperglycemia-induced podocyte apoptosis and injury, and other investigations have shown that in animal models of diabetic nephropathy, MSCs reduced glomerulosclerosis and oxidative stress 18, 20, 25, 26 . We also previously demonstrated the beneficial effect of EPC and MSC transplantation in a porcine model of renovascular hypertension, wherein intrarenal delivery of cells attenuated renovascular hypertension-induced myocardial injury and decreased renal injury 19, 27, 28 …”

“…In a systematic review and meta-analysis of 71 articles in animal models, Papazova et al 20 found that cell-based therapy reduced development and progression of CKD. This was evidenced by decreases in urinary protein and urea, which structurally associated with glomerulosclerosis and interstitial fibrosis.…”

“…However, while EPCs and MSCs were identified as the most effective cell types for CKD therapy 20 , these cells themselves are not impervious to damage and wear. Cell loss and dysfunction may manifest by impaired circulating cell count and pro-angiogenic or anti-inflammatory functionality.…”

Prospect of alternative therapies to kidney transplantation

“…A meta-analysis of the effect of stem cells on chronic kidney disease (CKD) showed beneficial effect, which might give hope to ESRD cases, as the CKD in the study had various grades and some of them represent chronic renal failure. 3 In the beginning of stem cell therapy, it was postulated that the stem cells would home to the damaged area and differentiate into the needed cells to replace the damaged cells. However, most tracing studies showed that most of the stem cells did not replace the damaged cells.…”