Endothelial differentiation potential of human monocyte-derived multipotential cells

Masataka Kuwana, Yuka Okazaki, Hiroaki Kodama, Takashi Satoh, Yutaka Kawakami, Yasuo Ikeda

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

We previously reported a unique CD14+CD45+CD34 + type I collagen+ cell fraction derived from human circulating CD14+ monocytes, named monocyte-derived multipotential cells (MOMCs). This primitive cell population contains progenitors capable of differentiating along the mesenchymal and neuronal lineages. Here, we investigated whether MOMCs can also differentiate along the endothelial lineage. MOMCs treated with angiogenic growth factors for 7 days changed morphologically and adopted a caudate appearance with rod-shaped microtubulated structures resembling Weibel-Palade bodies. Almost every cell expressed CD31, CD144, vascular endothelial growth factor (VEGF) type 1 and 2 receptors, Tie-2, von Willebrand factor (vWF), endothelial nitric-oxide synthase, and CD146, but CD14/CD45 expression was markedly downregulated. Under these culture conditions, the MOMCs continued to proliferate for up to 7 days. Functional characteristics, including vWF release upon histamine stimulation and upregulated expression of VEGF and VEGF type 1 receptor in response to hypoxia, were indistinguishable between the MOMC-derived endothelial-like cells and cultured mature endothelial cells. The MOMCs responded to angiogenic stimuli and promoted the formation of mature endothelial cell tubules in Matrigel cultures. Finally, in xenogenic transplantation studies using a severe combined immunodeficient mouse model, syngeneic colon carcinoma cells were injected subcutaneously with or without human MOMCs. Cotransplantation of the MOMCs promoted the formation of blood vessels, and more than 40% of the tumor vessel sections incorporated human endothelial cells derived from MOMCs. These findings indicate that human MOMCs can proliferate and differentiate along the endothelial lineage in a specific permissive environment and thus represent an autologous transplantable cell source for therapeutic neovasculogenesis.

Original languageEnglish
Pages (from-to)2733-2743
Number of pages11
JournalStem Cells
Volume24
Issue number12
DOIs
Publication statusPublished - 2006 Dec 1

Keywords

  • Endothelial cells
  • Endothelial differentiation
  • Monocyte
  • Vascularization

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Endothelial differentiation potential of human monocyte-derived multipotential cells'. Together they form a unique fingerprint.

  • Cite this

    Kuwana, M., Okazaki, Y., Kodama, H., Satoh, T., Kawakami, Y., & Ikeda, Y. (2006). Endothelial differentiation potential of human monocyte-derived multipotential cells. Stem Cells, 24(12), 2733-2743. https://doi.org/10.1634/stemcells.2006-0026