Yang Liu1, Sydney C W Tang1. 1. Division of Nephrology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, SAR, China.
Abstract
BACKGROUND: Diabetic nephropathy (DN) represents the leading cause of end-stage renal disease. Current therapeutic strategies for DN are very limited, and none of them can stop end-stage renal disease progression. Stem cell-based therapy showed encouraging outcomes in kidney disease, including experimental DN. SUMMARY: Both podocytes and proximal tubular epithelial cells play key roles in the pathogenesis of DN and, accordingly, could be regarded as treatment targets. Multiple kinds of stem cells contribute to the regeneration of the injured kidney, including embryonic stem cells (ESCs), mesenchymal stem cells, and induced pluripotent stem cells (iPSCs). Stem cells exert reparatory effects mainly by homing to injured sites, directing differentiation, paracrine action, and immunoregulation. However, poor survival after transplantation under diabetic conditions and unsatisfactory animal models of advanced DN are major obstacles for achieving an efficacious therapeutic effect from stem cell transplantation. Recently, remarkable progress has been made both in the direct differentiation of human ESCs and iPSCs into renal cells and in the generation of tissue- and patient-specific iPSCs, offering a powerful tool to investigate DN mechanisms and to identify the ideal candidate cell for future clinical application. KEY MESSAGE: This review provides updated information on recent progress and limitations of stem cell-based therapy for DN.
BACKGROUND:Diabetic nephropathy (DN) represents the leading cause of end-stage renal disease. Current therapeutic strategies for DN are very limited, and none of them can stop end-stage renal disease progression. Stem cell-based therapy showed encouraging outcomes in kidney disease, including experimental DN. SUMMARY: Both podocytes and proximal tubular epithelial cells play key roles in the pathogenesis of DN and, accordingly, could be regarded as treatment targets. Multiple kinds of stem cells contribute to the regeneration of the injured kidney, including embryonic stem cells (ESCs), mesenchymal stem cells, and induced pluripotent stem cells (iPSCs). Stem cells exert reparatory effects mainly by homing to injured sites, directing differentiation, paracrine action, and immunoregulation. However, poor survival after transplantation under diabetic conditions and unsatisfactory animal models of advanced DN are major obstacles for achieving an efficacious therapeutic effect from stem cell transplantation. Recently, remarkable progress has been made both in the direct differentiation of human ESCs and iPSCs into renal cells and in the generation of tissue- and patient-specific iPSCs, offering a powerful tool to investigate DN mechanisms and to identify the ideal candidate cell for future clinical application. KEY MESSAGE: This review provides updated information on recent progress and limitations of stem cell-based therapy for DN.
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