Human Umbilical Cord Blood Serum Improves Gentamicin-Induced Acute Kidney Injury

Objective:

Acute kidney injury (AKI) is a type of tissue damage in which there is fibrosis and gradual dysfunction of the kidney. In mild to moderate stages of the disease, kidney function can be restored. Human umbilical cord blood serum (HUCBS) contains various interleukins and growth factors that are directly involved in nephroprotective processes. The present study has examined the preventional effects of HUCBS against AKI-induced fibrosis.

Material and Methods:

The total protein and growth factor levels in HUCBS were quantified using BCA and ELISA kits. The effects of HUCBS on cell viability and migration were evaluated using human dermal fibroblasts (HDFs). For this, gentamicin- exposed HDFs were treated with 2%, 5%, and 10% HUCBS, as well as 10% FBS and 5% PL sera, in the culture medium. Adult male C57BL/6 mice were divided into control, 100 mg/kg gentamicin (AKI), and AKI+HUCBS groups. AKI was induced by intraperitoneal injection once daily for 7 days. In the serum-treated group, mice received 500 µl of HUCBS intravenously on the second day after the gentamicin injection. Serum samples were assessed for urea and creatinine. Fibrosis was assessed by western blotting for fibronectin and vimentin. Histopathological scores were evaluated using H&E staining.

Results:

Growth factors such as HDF, EGF, IGF, PDGF, and VEGF were present at high concentrations in HUCBS. Human cord blood serum at 10% increased the survival rate of cells exposed to 1500 µg/ml gentamicin compared with other sera. However, it did not affect cell migration. Urea and creatinine levels in the AKI+HUCBS group were lower than in the AKI group, and BUN/Cr was increased in this group. The AKI group showed a 4.5-fold increase in fibronectin, whereas it was reduced to nearly zero in the AKI+HUCBS group. The AKI+HUCBS group also showed a nearly 2-fold increase in vimentin compared with the AKI group. Histopathological studies showed tubular injury and cast formation in the AKI group, but not in the HUCBS-treated group.

Conclusion:

HUCBS can prevent the progression of fibrosis after acute kidney injury.

Keyword:

HUCBS, AKI, Gentamicin, Kidney, Growth factors

Seyedeh Ghadireh Mirabolghasemi ^{1, 2}, Farhad Mostafaei ², Elham Yektadoost ², Mohammad Hossein Ghanaian ², Reza Moghadasali ²

1. Department of Cellular and Developmental Biology, Faculty of Biosciences and Emerging Technologies, University of Science and Culture, Tehran, Iran

2. Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran