Fig. 1. Therapeutically administered FRCs impart a survival benefit after LPS endotoxemia or CLP sepsis induction.

In all experiments, stated groups received a single intraperitoneal dose of FRCs ex vivo expanded from sex-matched mice or saline (vehicle alone control). All CLP mice received standard of care, that is, antibiotics administered from the time of FRC administration and maintained throughout the experiment, and fluid resuscitation at the time of surgery. (A) Schematic timeline of experimental setup and analyses for LPS and CLP sepsis studies. LN, lymph node. (B) C57BL6 mice aged 4 to 6 weeks received 350 μg of LPS in saline intraperitoneally. Four hours later, mice received 1 × 10⁶ syngeneic C57BL6-derived FRCs (n = 5), bone marrow MSCs (n = 7), or vehicle (saline, n = 5) intraperitoneally and were monitored for survival. (C) Aged C57BL6 mice (18 to 24 months age-matched between groups) received 150 μg of LPS intraperitoneally, and 4 hours later, this was followed by a single intraperitoneal injection of 1 × 10⁶ syngeneic FRCs derived from 4- to 6-week-old C57BL6 mice (n = 6) or vehicle (saline, n = 10). Mice were monitored for survival. (D) CLP sepsis was induced in C57BL6 mice aged 4 to 6 weeks. Four hours later, mice received a single dose of 1 × 10⁶ autologous FRCs (n = 5) or vehicle (saline, n = 13) intraperitoneally. (E) CLP sepsis was induced in BALB/c mice aged 4 to 6 weeks. Mice received a single dose of allogeneic C57BL6-derived FRCs (n = 18), bone marrow MSCs (n = 7), or vehicle (saline, n = 21) intraperitoneally at 4 hours and were monitored for survival. (F) BALB/c mice aged 4 to 6 weeks received a single dose of 1 × 10⁶ allogeneic C57BL6-derived FRCs (n = 9) or saline (n = 10) intraperitoneally 16 hours after CLP surgery. Mice were monitored for survival. All data depict a minimum of two independent experiments. The log-rank (Mantel-Cox) test was used to test for significance. Arrows depict the time of cell administration.