Low-Energy Shockwave Treatment Promotes Endothelial Progenitor Cell Homing to the Stenotic Pig Kidney

Yu Zhao, Adrian Santelli, Xiang Yang Zhu, Xin Zhang, John R. Woollard, Xiao Jun Chen, Kyra L. Jordan, James Krier, Hui Tang, Ishran Saadiq, Amir Lerman, Lilach O. Lerman

Research output: Contribution to journalArticle

Abstract

Endothelial progenitor cells (EPCs) patrols the circulation and contributes to endothelial cell regeneration. Atherosclerotic renal artery stenosis (ARAS) induces microvascular loss in the stenotic kidney (STK). Low-energy shockwave therapy (SW) can induce angiogenesis and restore the STK microcirculation, but the underlying mechanism remains unclear. We tested the hypothesis that SW increases EPC homing to the swine STK, associated with capillary regeneration. Normal pigs and pigs after 3 wk of renal artery stenosis were treated with six sessions of low-energy SW (biweekly for three consecutive weeks) or left untreated. Four weeks after completion of treatment, we assessed EPC (CD34+/KDR+) numbers and levels of the homing-factor stromal cell-derived factor (SDF)-1 in the inferior vena cava and the STK vein and artery, as well as urinary levels of vascular endothelial growth factor (VEGF) and integrin-1β. Subsequently, we assessed STK morphology, capillary count, and expression of the proangiogenic growth factors angiopoietin-1, VEGF, and endothelial nitric oxide synthase ex vivo. A 3-wk low-energy SW regimen improved STK structure, capillary count, and function in ARAS+SW, and EPC numbers and gradients across the STK decreased. Plasma SDF-1 and renal expression of angiogenic factors were increased in ARAS+SW, and urinary levels of VEGF and integrin-1β tended to rise during the SW regimen. In conclusion, SW improves ischemic kidney capillary density, which is associated with, and may be at least in part mediated by, promoting EPCs mobilization and homing to the stenotic kidney.

Original languageEnglish (US)
Pages (from-to)963689720917342
JournalCell transplantation
Volume29
DOIs
StatePublished - Jan 1 2020

Keywords

  • capillary
  • endothelial progenitor cells
  • low-energy shockwave
  • renal artery stenosis

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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    Zhao, Y., Santelli, A., Zhu, X. Y., Zhang, X., Woollard, J. R., Chen, X. J., Jordan, K. L., Krier, J., Tang, H., Saadiq, I., Lerman, A., & Lerman, L. O. (2020). Low-Energy Shockwave Treatment Promotes Endothelial Progenitor Cell Homing to the Stenotic Pig Kidney. Cell transplantation, 29, 963689720917342. https://doi.org/10.1177/0963689720917342