Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease

Author(s)

Ribeiro, Patricia de Carvalho ^[1] ; Lojudice, Fernando Henrique ^[2] ; Fernandes-Charpiot, Ida Maria Maximina ^{[1, 3]} ; Baptista, Maria Alice Sperto Ferreira ^{[1, 3]} ; de Almeida Araujo, Stanley ^{[4, 5]} ; Mendes, Gloria Elisa Florido ^[1] ; Sogayar, Mari Cleide ^{[6, 2]} ; Abbud-Filho, Mario ^{[1, 3]} ; Caldas, Heloisa Cristina ^{[1, 3]}

Affiliation

^[1] FAMERP Med Sch, Dept Med, Lab Immunol & Expt Transplantat LITEX, Sao Jose Do Rio Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Med, Cell & Mol Therapy Ctr NUCEL, Sao Paulo, SP - Brazil

^[3] FAMERP FUNFARME, Hosp Base, Kidney Transplant Unit, Sao Jose Do Rio Preto, SP - Brazil

^[4] Univ Fed Minas Gerais, Ctr Microscopia Eletron, Horizonte - Brazil

^[5] Inst Nefropatol, Belo Horizonte, MG - Brazil

^[6] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: STEM CELL RESEARCH & THERAPY; v. 11, n. 1 DEC 9 2020.
• Web of Science Citations: 0

Abstract

BackgroundChronic kidney disease (CKD) is a global public health problem. Cell therapy using pluripotent stem cells represents an attractive therapeutic approach for the treatment of CKD.MethodsWe transplanted mitomycin C (MMC)-treated human induced pluripotent stem cells (hiPSCs) and renal progenitor cells (RPCs) into a CKD rat model system. The RPC and hiPSC 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 45days post-surgery.ResultsWe successfully generated 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. After cell transplantation into CKD rats, the body weight change was significantly increased in both hiPSC and RPC groups, in comparison with the control group. Creatinine clearance (CCr) was preserved only in the hiPSC group. Similarly, the number of macrophages in the kidneys of the hiPSC group reached a statistically significant reduction, when compared to control rats. Both treatments reduced positive staining for the marker alpha -smooth muscle actin. Histological features showed decreased tubulointerstitial damage (interstitial fibrosis and tubular atrophy) as well as a reduction in glomerulosclerosis in both iPSC and RPC groups.ConclusionsIn conclusion, we describe that both MMC-treated hiPSCs and RPCs exert beneficial effects in attenuating CKD progression. Both cell types were equally efficient to reduce histological damage and weight loss caused by CKD. hiPSCs seem to be more efficient than RPCs, possibly due to a paracrine effect triggered by hiPSCs. These results demonstrate that the use of MMC-treated hiPSCs and RPCs improves clinical and histological CKD parameters, avoided tumor formation, and therefore may be a promising cell therapy strategy for CKD. (AU)

• FAPESP's process: 16/18586-0 - In vitro differentiation of induced pluripotent stem cells (iPS) in renal progenitor cells and their effect on treatment of experimental chronic renal failure
• Grantee: Heloisa Cristina Caldas
• Support Opportunities: Regular Research Grants