Hydrogel-embedded endothelial progenitor cells evade LPS and mitigate endotoxemia

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&#...

Full description

Saved in:
Bibliographic Details
Published in:American journal of physiology. Renal physiology 2011-10, Vol.301 (4), p.F802-F812
Main Authors: Ghaly, Tammer, Rabadi, May M, Weber, Mia, Rabadi, Seham M, Bank, Michael, Grom, John M, Fallon, John T, Goligorsky, Michael S, Ratliff, Brian B
Format: Article
Language:English
Subjects:
Animals
Blood Pressure - drug effects
Endothelial Cells - transplantation
Endotoxemia - therapy
Hydrogels
Hydrogels - administration & dosage
Kidney - blood supply
Lipopolysaccharides - immunology
Male
Mice
Microcirculation
Neovascularization, Physiologic
Physiology
Rodents
Sepsis
Stem Cell Transplantation
Tissue Embedding
Toxins
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1931-857X
1522-1466
DOI:10.1152/ajprenal.00124.2011