Combination of Nonwoven Filters and Mesenchymal Stem Cells Reduced Glomerulosclerotic Lesions in Rat Chronic Kidney Disease Models

摘要

Background and Objectives: The increasing incidence of patients requiring hemodialysis has become a medical and economic problem globally; it is necessary to maintain renal glomerulus functionality to prevent the progression of chronic kidney disease. As a therapeutic tool for preventing the progression of chronic kidney disease, mesenchymal stem cells (MSCs) are a promising source of both growth factors and cells for regeneration. However, the escape of MSCs from injection sites, as well as the insufficient production of growth factors, is issues that remain unresolved. In the present study, a complex of cells and a nonwoven filter was localized in an injured kidney to provide growth factors such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). Methods and Results: Nonwoven biodegradable polylactic acid (PLA) filters were used to capture rat bone marrow stem cells (r-BMSCs). The capture rates of r-BMSCs on five PLA filter disks were over 85%. The production of HGF by r-BMSCs on PLA filters was markedly enhanced through interactions between the cells and the nonwoven filter. Conversely, the production of VEGF by r-BMSC on PLA filters was unchanged. Complexes of nonwoven filters and cells were implanted onto the surfaces of kidneys of 5/6-nephrectomized rats, which are characterized by progressive glomerulosclerosis. Within the r-BMSC/PLA complexes, deleterious changes in serum creatinine levels were not attenuated. However, PLA filters with r-BMSCs, which enhanced HGF production over 4 weeks of culture, significantly (P = 0.03) decreased urinary protein levels at 4 weeks after implantation compared to untreated nephrectomized rats. Further histopathological studies revealed that glomerulosclerotic lesions were significantly (P = 0.008) reduced by treatment with the r-BMSC/PLA complex. Conclusion: Devices made of PLA nonwoven filters and stem cells are potentially useful for the prevention and treatment of chronic kidney disease.