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Induced pluripotent stem cell-derived endothelial progenitor cells attenuate ischemic acute kidney injury and cardiac

Wen-Ching Shen1,2, Yu-Hsiang Chou2,3,4, Hsiang-Po Huang5,6

  • 1Drug Development Center, Institute of New Drug Development, Institute of Biomedical Sciences, China Medical University, Taichung, 404, Taiwan.

Stem Cell Research & Therapy
|December 12, 2018
PubMed
Abstract

Insights

Human induced pluripotent stem cell-derived endothelial progenitor cells (iEPCs) treat acute kidney injury (AKI) and cardiac dysfunction. This therapy repairs kidney endothelial cells and reduces heart cell apoptosis in AKI mice.

Area of Science:

  • Regenerative Medicine
  • Cardiovascular Biology
  • Nephrology

Background:

  • Renal ischemia-reperfusion (I/R) injury is a primary cause of acute kidney injury (AKI), leading to significant morbidity and mortality.
  • Effective treatments for AKI are lacking, and the molecular mechanisms linking kidney injury to distant organ damage are not fully understood.
  • Novel therapeutic strategies are crucial for managing AKI and its systemic complications.

Purpose of the Study:

  • To investigate the therapeutic potential of human induced pluripotent stem cell-derived endothelial progenitor cells (iEPCs) in a mouse model of renal I/R injury.
  • To evaluate the efficacy of iEPC therapy in ameliorating AKI and associated remote cardiac dysfunction.
  • To elucidate the mechanisms underlying iEPC-mediated protection.

Main Methods:

  • Human induced pluripotent stem cells were differentiated into iEPCs.
  • A mouse model of AKI was established using renal I/R injury.
  • iEPCs were intravenously infused into AKI mice to assess their therapeutic effects.
  • Kidney function, histology, cardiac function, and molecular markers were analyzed.

Main Results:

  • Intravenously infused iEPCs engrafted into the injured kidney, expressed CD31, and replaced damaged endothelial cells.
  • iEPC therapy significantly reduced blood urea nitrogen and creatinine levels in AKI mice.
  • Treatment with iEPCs attenuated tubular injury, apoptosis, and capillary rarefaction in the kidneys.
  • Cardiac apoptosis and dysfunction were ameliorated in AKI mice treated with iEPCs, with reduced serum brain natriuretic peptide levels.
  • iEPC therapy downregulated caspase-3 and upregulated Bcl-2 in the heart, potentially by reducing indoxyl sulfate and interleukin-1β.

Conclusions:

  • Human iPS cell-derived iEPCs demonstrate protective effects against ischemic AKI.
  • iEPC therapy mitigates remote cardiac dysfunction in the context of AKI.
  • The therapeutic benefits involve endothelial cell repair in the kidney and attenuation of cardiomyocyte apoptosis, possibly via modulation of specific molecular pathways.
Keywords:
Acute kidney injuryCardiac dysfunctionEndothelial progenitor cellsIndoxyl sulfateInduced pluripotent stem cells

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