Hydrogel-embedded endothelial progenitor cells evade LPS and mitigate endotoxemia.

Area of Science:

• Biomedical Engineering
• Immunology
• Regenerative Medicine

Background:

• Sepsis, a life-threatening condition, often leads to circulatory dysfunction and poor outcomes.
• Lipopolysaccharide (LPS) triggers endotoxemia, causing vascular injury and impacting endothelial progenitor cells (EPCs).
• Increased circulating EPCs correlate with survival in endotoxemia, suggesting a role in vascular repair.

Purpose of the Study:

• To investigate the functional capacity of EPCs during endotoxemia.
• To determine if adoptive transfer of EPCs can ameliorate hemodynamic and organ dysfunction in a murine model of endotoxemia.
• To evaluate the efficacy of EPCs delivered via hyaluronic acid (HA) hydrogels.

Main Methods:

• Modeled endotoxemia using lipopolysaccharide (LPS) injection in mice.
• Assessed EPC clonogenic potential and LPS-induced cytotoxicity via Toll-like receptor 4 (TLR4).
• Administered intact EPCs intravenously or embedded in pronectin-coated HA hydrogels to LPS-injected mice.

Main Results:

• EPCs from endotoxemic mice showed impaired function; LPS exhibited TLR4-mediated cytotoxicity.
• Embedding EPCs in HA hydrogels mitigated LPS-induced cytotoxicity.
• Adoptive EPC transfer improved blood pressure control, reduced hepatocellular and renal dysfunction, and restored renal microcirculation.
• EPC therapy was most effective when cells were delivered within HA hydrogels.

Conclusions:

• Endotoxemia-induced EPC incompetence contributes significantly to hemodynamic and renal dysfunction.
• Adoptive transfer of EPCs, especially when encapsulated in HA hydrogels, offers therapeutic benefits for endotoxemia.
• This study highlights the potential of EPC-based therapy for sepsis complications.