Targeting Murine Mesenchymal Stem Cells to Kidney Injury Molecule-1 Improves Their Therapeutic Efficacy in Chronic Ischemic Kidney Injury

Xiangyu Zou, Kai Jiang, Amrutesh S. Puranik, Kyra L. Jordan, Hui Tang, Xiangyang Zhu, Lilach O. Lerman

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Mesenchymal stem cells (MSC) have been experimentally used for kidney repair, but modest retention limits their efficacy. Cell-surface coating allows modulating MSC homing and interaction with target cells. We coated mouse adipose tissue-derived MSC with antibodies directed against kidney injury molecule-1 (ab-KIM1), which is upregulated in injured kidneys, and tested the hypothesis that this would enhance their therapeutic effects in ischemic kidney injury. Untreated MSC, ab-KIM1-coated MSC (KIM-MSC), or vehicle, were injected systemically into the carotid artery of 2-kidneys, 1-clip mice 2 weeks after surgery. MSC retention in different organs was explored 24 hours, 48 hours, or 2 weeks after injection. Renal volume, perfusion, and oxygenation were studied 2 weeks after injection using magnetic resonance imaging in vivo, and renal inflammation, apoptosis, capillary density, and fibrosis ex vivo. The ab-KIM1 coating had little effect on MSC viability or proliferation. The stenotic kidney showed upregulated KIM1 expression, selective homing, and greater retention of KIM-MSC compared to untreated MSC and compared to other organs. KIM-MSC-injected mice improved renal perfusion and capillary density, and attenuated oxidative damage, apoptosis, and fibrosis compared to mice treated with vehicle or with native MSC. In conclusion, MSC coating with ab-KIM1 increased their retention in the ischemic kidney and enhanced their therapeutic efficacy. This novel method may be useful to selectively target injured kidneys, and supports further development of strategies to enhance cell-based treatment of ischemic kidney injury. Stem Cells Translational Medicine 2018;7:394–403.

Original languageEnglish (US)
Pages (from-to)394-403
Number of pages10
JournalStem Cells Translational Medicine
Volume7
Issue number5
DOIs
StatePublished - May 2018

Keywords

  • Cell coating
  • Kidney injury molecule-1
  • Mesenchymal stem cell
  • Renal artery stenosis

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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