Intravenously injected human multilineage-differentiating stress-enduring cells selectively engraft into mouse aortic aneurysms and attenuate dilatation by differentiating into multiple cell types

Katsuhiro Hosoyama, Shohei Wakao, Yoshihiro Kushida, Fumitaka Ogura, Kay Maeda, Osamu Adachi, Shunsuke Kawamoto, Mari Dezawa, Yoshikatsu Saiki

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objectives: Aortic aneurysms result from the degradation of multiple components represented by endothelial cells, vascular smooth muscle cells, and elastic fibers. Cells that can replenish these components are desirable for cell-based therapy. Intravenously injected multilineage-differentiating stress-enduring (Muse) cells, endogenous nontumorigenic pluripotent-like stem cells, reportedly integrate into the damaged site and repair the tissue through spontaneous differentiation into tissue-compatible cells. We evaluated the therapeutic efficacy of Muse cells in a murine aortic aneurysm model. Methods: Human bone marrow Muse cells, isolated as stage-specific embryonic antigen-3+ from bone marrow mesenchymal stem cells, or non-Muse cells (stage-specific embryonic antigen-3- cells in mesenchymal stem cells), bone marrow mesenchymal stem cells, or vehicle was intravenously injected at day 0, day 7, and 2 weeks (20,000 cells/injection) after inducing aortic aneurysms by periaortic incubation of CaCl2 and elastase in severe combined immunodeficient mice. Results: At 8 weeks, infusion of human Muse cells attenuated aneurysm dilation, and the aneurysmal size in the Muse group corresponded to approximately 62.5%, 55.6%, and 45.6% in the non-Muse, mesenchymal stem cell, and vehicle groups, respectively. Multiphoton laser confocal microscopy revealed that infused Muse cells migrated into aneurysmal tissue from the adventitial side and penetrated toward the luminal side. Histologic analysis demonstrated robust preservation of elastic fibers and spontaneous differentiation into endothelial cells and vascular smooth muscle cells. Conclusions: After intravenous injection, Muse cells homed and expanded to the aneurysm from the adventitial side. Subsequently, Muse cells differentiated spontaneously into vascular smooth muscle cells and endothelial cells, and elastic fibers were preserved. These Muse cell features together led to substantial attenuation of aneurysmal dilation.

Original languageEnglish
Pages (from-to)2301-2313.e4
JournalJournal of Thoracic and Cardiovascular Surgery
Volume155
Issue number6
DOIs
Publication statusPublished - 2018 Jun

Keywords

  • Muse cell
  • aortic aneurysm
  • mesenchymal stem cell
  • stem cell therapy

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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