Bone marrow-derived cells serve as proangiogenic macrophages but not endothelial cells in wound healing

Yuji Okuno, Ayako Nakamura-Ishizu, Kazuo Kishi, Toshio Suda, Yoshiaki Kubota

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Bone marrow-derived cells (BMDCs) contribute to postnatal vascular growth by differentiating into endothelial cells or secreting angiogenic factors. However, the extent of their endothelial differentiation highly varies according to the angiogenic models used. Wound healing is an intricate process in which the skin repairs itself after injury. As a process also observed in cancer progression, neoangiogenesis into wound tissues is profoundly involved in this healing process, suggesting the contribution of BMDCs. However, the extent of the differentiation of BMDCs to endothelial cells in wound healing is unclear. In this study, using the green fluorescent protein-bone marrow chimeric experiment and high resolution confocal microscopy at a single cell level, we observed no endothelial differentiation of BMDCs in 2 acute wound healing models (dorsal excisional wound and ear punch) and a chronic wound healing model (decubitus ulcer). Instead, a major proportion of BMDCs were macrophages. Indeed, colony-stimulating factor 1 (CSF-1) inhibition depleted approximately 80% of the BMDCs at the wound healing site. CSF-1-mutant (CSF-1op/op) mice showed significantly reduced neoangiogenesis into the wound site, supporting the substantial role of BMDCs as macrophages. Our data show that the proangiogenic effects of macrophages, but not the endothelial differentiation, are the major contribution of BMDCs in wound healing.

Original languageEnglish
Pages (from-to)5264-5272
Number of pages9
JournalBlood
Volume117
Issue number19
DOIs
Publication statusPublished - 2011 May 12

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Macrophages
Endothelial cells
Bone Marrow Cells
Wound Healing
Bone
Endothelial Cells
Macrophage Colony-Stimulating Factor
Wounds and Injuries
Pressure Ulcer
Angiogenesis Inducing Agents
Confocal microscopy
Green Fluorescent Proteins
Confocal Microscopy
Ear
Blood Vessels
Bone Marrow
Skin
Repair
Tissue
Growth

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Bone marrow-derived cells serve as proangiogenic macrophages but not endothelial cells in wound healing. / Okuno, Yuji; Nakamura-Ishizu, Ayako; Kishi, Kazuo; Suda, Toshio; Kubota, Yoshiaki.

In: Blood, Vol. 117, No. 19, 12.05.2011, p. 5264-5272.

Research output: Contribution to journalArticle

Okuno, Yuji ; Nakamura-Ishizu, Ayako ; Kishi, Kazuo ; Suda, Toshio ; Kubota, Yoshiaki. / Bone marrow-derived cells serve as proangiogenic macrophages but not endothelial cells in wound healing. In: Blood. 2011 ; Vol. 117, No. 19. pp. 5264-5272.
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