Interaction of a specific population of human embryonic stem cell-derived progenitor cells with CD11b+ cells ameliorates sepsis-induced lung inflammatory injury

Sophie P. Toya, Fei Li, Marcelo G. Bonini, Ignatius Gomez, Mao Mao, Kurt W. Bachmaier, Asrar B. Malik

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Human embryonic stem cells differentiated under mesoderm-inducing conditions have important therapeutic properties in sepsis-induced lung injury in mice. Single cell suspensions obtained from day 7 human embryoid bodies (d7EBs) injected i.v. 1 hour after cecal ligation and puncture significantly reduced lung inflammation and edema as well as production of tumor necrosis factor-α and interferon-γ in lungs compared with controls, whereas interleukin-10 production remained elevated. d7EB cell transplantation also reduced mortality to 50% from 90% in the control group. The protection was ascribed to d7EB cell interaction with lung resident CD11b+ cells, and was correlated with the ability of d7EB cells to reduce it also reduced production of proinflammatory cytokines by CD11+ cells, and to endothelial NO synthase-derived NO by d7EB cells, leading to inhibition of inducible macrophage-type NO synthase activation in CD11b+ cells. The protective progenitor cells were positive for the endothelial and hematopoietic lineage marker angiotensin converting enzyme (ACE). Only the ACE+ fraction modulated the proinflammatory profile of CD11b+ cells and reduced mortality in septic mice. In contrast to the nonprotective ACE-cell fraction, the ACE+ cell fraction also produced NO. These findings suggest that an ACE+ subset of human embryonic stem cell-derived progenitor cells has a highly specialized anti-inflammatory function that ameliorates sepsis-induced lung inflammation and reduces mortality.

Original languageEnglish (US)
Pages (from-to)313-324
Number of pages12
JournalAmerican Journal of Pathology
Volume178
Issue number1
DOIs
StatePublished - Jan 2011

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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