Título

GENERATED OF HUMAN INDUCED PLURIPOTENT STEM CELLS AND RENAL PROGENITOR CELLS IN EXPERIMENTAL CHRONIC KIDNEY DISEASE.

Resumo

Background Regenerative medicine using pluripotent stem cells represents an attractive therapeutic approach for treatment of chronic kidney disease (CKD) in its different stages. Methods We transplanted Mitomycin C (MMC)-treated human induced pluripotent stem cells (hiPSCs) and renal progenitors cells (RPCs) into the CKD rat model system. The RPCs and hiPSCs cells were characterized by immunofluorescence and qRT-PCR. Untreated 5/6 nephrectomized rats were compared to CKD animals receiving the same amount of MMC-treated hiPSCs or RPCs. Renal function, histology, and immunohistochemistry were evaluated 45 days post-surgery. Results Initially we successfully generate hiPSCs from peripheral blood and differentiated them into RPCs expressing renal progenitor genes (PAX2, WT1, SIX2, and SALL1) and podocyte-related genes (SYNPO, NPHS1). RPCs also exhibited reduced OCT4 expression, confirming the loss of pluripotency. These cells when transplanted into CKD rats, caused a significant increase in body weight change in both hiPSC and RPC groups, in comparison with the control group. Creatinine clearance (CCr) was preserved only in the hiPSC group as well as was significantly lower the number of macrophages in the rat kidneys treated with hiPSC. Both treatments reduced positive staining for the marker α-smooth muscle actin. Histological features showed decreased tubulointerstitial damage (interstitial fibrosis and tubular atrophy) as well as the glomerulosclerosis. Conclusions In conclusion, we observed that MMC-treated hiPSCs and RPCs, both had beneficial effects to attenuate CKD progression. Both types of cells were equally efficient to reduce histological damage and weight loss caused by CKD. hiPSC seemed to be more efficient than RPCs suggesting different anti-inflammatory mechanisms. These results demonstrate that the use of MMC-treated hiPSCs and RPCs improved clinical and histological parameters, avoided tumor formation, and therefore may be promising cell therapy strategies for CKD.

Área

Doença Renal Crônica

Autores

HELOISA C CALDAS, Patrícia de Carvalho Ribeiro, Fernando Henrique Lojudice, Stanley De Almeida Araujo, Ida Maria Maximina Fernandes-Charpiot, Maria Alice Ferreira Baptista, Mari Cleide Sogayar, Gloria Elisa Florido Mendes, Heloisa Cristina Caldas, Mario Abbud-Filho