Generation of Urine-Derived Induced Pluripotent Stem Cell Line from Patients with Acute Kidney Injury

Cell Reprogram. 2021 Oct;23(5):290-303. doi: 10.1089/cell.2021.0051.

Abstract

Acute kidney injury (AKI) is mainly characterized by rapid decline of renal function. Currently, the strategy of stem cells might be a therapy to treat AKI. The objective of this study was to obtain human urine-derived cells (HUCs) from patients with AKI, followed by establishing induced pluripotent stem (iPS) cell line. We isolated urine cells from patients with AKI and found that the cells could survive long term with epithelioid morphology and maintain a normal karyotype. The cell line had expression of renal-specific markers and renal development-related genes. After induction, the urine cells cotransfecting with TET-ON vectors were converted into iPS cells. The HUC-derived iPS (HUC-iPS) was positive for alkaline phosphatase staining, and had expression of pluripotency markers, consistent with human embryonic fibroblast-derived iPS cell. Notably, HUC-iPS could be induced to undergo directional kidney precursor cells (KPCs) differentiation under defined conditions, and transplantation of KPCs resulted in reducing kidney damage from ischemia-reperfusion injury in mice. Therefore, we successfully established HUC-iPS cell from patients with AKI and provided a novel stem cell resource for cell therapy in AKI.

Keywords: TET-ON vectors; acute kidney injury; human urine-derived renal cell; induced pluripotent stem cell line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / therapy*
  • Animals
  • Cell Differentiation
  • Cell- and Tissue-Based Therapy / methods*
  • Epithelial Cells / cytology
  • Fibroblasts / cytology*
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Kidney / cytology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Reperfusion Injury / complications*
  • Stem Cell Transplantation
  • Urine / chemistry*