Brief report: Mechanism of extravasation of infused stem cells

Ke Cheng, Deliang Shen, Yucai Xie, Eugenio Cingolani, Konstantinos Malliaras, Eduardo Marbán

Research output: Contribution to journalArticle

Abstract

In order for bloodborne stem cells to be effective in tissue regeneration, cells must cross vessel walls and enter the parenchyma. Although such transmigration does occur, the mechanism remains elusive. Leukocytes invade tissue by diapedesis; stem cells are commonly assumed to do likewise, but evidence is lacking. Cardiac-derived regenerative cells and multicellular cardiospheres (CSPs) were infused into the coronary vessels of rat hearts. Serial histology revealed a novel mechanism of cell transmigration, "active vascular expulsion," which underlies the extravasation of infused cells and cell aggregates. In this mechanism, the vascular barrier undergoes extensive remodeling, while the cells themselves are relatively passive. The mechanism was confirmed in vivo by serial intravital microscopy of CSP extravasation in a dorsal skin flap model. Integrins and matrix metalloproteinases play critical roles in active vascular expulsion. In vitro models revealed that active vascular expulsion is generalizable to other stem cell types and to breast cancer cells. Recognition of active vascular expulsion as a mechanism for transvascular cell migration opens new opportunities to enhance the efficacy of vascularly delivered cell therapy.

Original languageEnglish (US)
Pages (from-to)2835-2842
Number of pages8
JournalStem Cells
Volume30
Issue number12
DOIs
StatePublished - Dec 2012
Externally publishedYes

Fingerprint

Stem Cells
Blood Vessels
Transendothelial and Transepithelial Migration
Cell- and Tissue-Based Therapy
Matrix Metalloproteinases
Integrins
Cell Movement
Regeneration
Coronary Vessels
Histology
Leukocytes
Breast Neoplasms
Skin

Keywords

  • Cell adhesion molecules
  • Cell migration
  • Extravasation
  • Metalloproteinases
  • Vasculature

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Cheng, K., Shen, D., Xie, Y., Cingolani, E., Malliaras, K., & Marbán, E. (2012). Brief report: Mechanism of extravasation of infused stem cells. Stem Cells, 30(12), 2835-2842. https://doi.org/10.1002/stem.1184

Brief report : Mechanism of extravasation of infused stem cells. / Cheng, Ke; Shen, Deliang; Xie, Yucai; Cingolani, Eugenio; Malliaras, Konstantinos; Marbán, Eduardo.

In: Stem Cells, Vol. 30, No. 12, 12.2012, p. 2835-2842.

Research output: Contribution to journalArticle

Cheng, K, Shen, D, Xie, Y, Cingolani, E, Malliaras, K & Marbán, E 2012, 'Brief report: Mechanism of extravasation of infused stem cells', Stem Cells, vol. 30, no. 12, pp. 2835-2842. https://doi.org/10.1002/stem.1184
Cheng K, Shen D, Xie Y, Cingolani E, Malliaras K, Marbán E. Brief report: Mechanism of extravasation of infused stem cells. Stem Cells. 2012 Dec;30(12):2835-2842. https://doi.org/10.1002/stem.1184
Cheng, Ke ; Shen, Deliang ; Xie, Yucai ; Cingolani, Eugenio ; Malliaras, Konstantinos ; Marbán, Eduardo. / Brief report : Mechanism of extravasation of infused stem cells. In: Stem Cells. 2012 ; Vol. 30, No. 12. pp. 2835-2842.
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