Hydrogel-embedded endothelial progenitor cells evade LPS and mitigate endotoxemia

T. Ghaly, May M. Rabadi, Mia Weber, Seham M. Rabadi, Michael Bank, John M. Grom, John T. Fallon, Michael S. Goligorsky, Brian B. Ratliff

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Sepsis and its complications are associated with poor clinical outcomes. The circulatory system is a well-known target of lipopolysaccharide (LPS). Recently, several clinical studies documented mobilization of endothelial progenitor cells (EPCs) during endotoxemia, with the probability of patients' survival correlating with the rise in circulating EPCs. This fact combined with endotoxemia-induced vascular injury led us to hypothesize that the developing functional EPC incompetence could impede vascular repair and that adoptive transfer of EPCs could improve hemodynamics in endotoxemia. We used LPS injection to model endotoxemia. EPCs isolated from endotoxemic mice exhibited impaired clonogenic potential and LPS exerted Toll-like receptor 4-mediated cytotoxic effects toward EPCs, which was mitigated by embedding them in hyaluronic acid (HA) hydrogels. Therefore, intact EPCs were either delivered intravenously or embedded within pronectin- coated HA hydrogels. Adoptive transfer of EPCs in LPS-injected mice improved control of blood pressure and reduced hepatocellular and renal dysfunction. Specifically, EPC treatment was associated with the restoration of renal microcirculation and improved renal function. EPC therapy was most efficient when cells were delivered embedded in HA hydrogel. These findings establish major therapeutic benefits of adoptive transfer of EPCs, especially when embedded in HA hydrogels, in mice with LPS-induced endotoxemia, and they argue that hemodynamic and renal abnormalities of endotoxemia are in significant part due to developing incompetence of endogenous EPCs.

Original languageEnglish
Pages (from-to)F802-F812
JournalAmerican Journal of Physiology - Renal Physiology
Volume301
Issue number4
DOIs
StatePublished - Oct 2011
Externally publishedYes

Keywords

  • Lipopolysaccharide
  • Microcirculation
  • Renal function
  • Sepsis
  • Stem cell therapy

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