Original Article
Transplantation of umbilical cord mesenchymal stem cells into mice with focal segmental glomerulosclerosis delayed disease manifestation
Abstract
Background: Familial focal segmental glomerulosclerosis (fFSGS) is difficult to treat, and stem cell transplantation is one of the most promising approaches for treating this condition. According to the novel mutation site found in our FSGS family, we established a novel animal model of FSGS to explore the application of stem cell therapy in FSGS.
Methods: The animal model used in this experiment was p.Gly1617Valfs X15 (C57BL/6) mutant mice. This mutation was first found in a focal segmental glomerulosclerosis (FSGS) family undergoing renal biopsy in our department. The mouse model was then constructed via CRISPR/Cas9 genomic editing technology. Then, the animals were injected with human umbilical cord mesenchymal stem cells (UCMSC) through the tail vein and regularly followed up to determine phenotypic changes in urine protein quantities, serum creatinine and histological outcomes.
Results: Compared with the positive control group, the levels of urinary protein and serum creatine were decreased significantly after UCMSC transplantation. HE staining images revealed a delay in glomerular sclerosis. Moreover, the secretion of the type IV collagen α3 chain was significantly increased compared with the positive control group, as shown by using immunofluorescence microscopic observation, and electron microscopy proved that the podocytes and basement membrane recovered well from the damage. The intervention also resulted in enhanced IL-22 expression.
Conclusions: UCMSC transplantation may be a potential treatment for FSGS, and IL-22 may play an important role in this process. Further studies are needed to reveal the underlying mechanism.
Methods: The animal model used in this experiment was p.Gly1617Valfs X15 (C57BL/6) mutant mice. This mutation was first found in a focal segmental glomerulosclerosis (FSGS) family undergoing renal biopsy in our department. The mouse model was then constructed via CRISPR/Cas9 genomic editing technology. Then, the animals were injected with human umbilical cord mesenchymal stem cells (UCMSC) through the tail vein and regularly followed up to determine phenotypic changes in urine protein quantities, serum creatinine and histological outcomes.
Results: Compared with the positive control group, the levels of urinary protein and serum creatine were decreased significantly after UCMSC transplantation. HE staining images revealed a delay in glomerular sclerosis. Moreover, the secretion of the type IV collagen α3 chain was significantly increased compared with the positive control group, as shown by using immunofluorescence microscopic observation, and electron microscopy proved that the podocytes and basement membrane recovered well from the damage. The intervention also resulted in enhanced IL-22 expression.
Conclusions: UCMSC transplantation may be a potential treatment for FSGS, and IL-22 may play an important role in this process. Further studies are needed to reveal the underlying mechanism.
