[Effect of bone marrow-derived mesenchymal stem cells transplantation on the inflammatory response and lung injury in rabbit with inhalation injury].

Objective: To study the effect of bone marrow-derived mesenchymal stem cells (MSC) transplantation on the major inflammatory cytokines content in peripheral blood, lung water mass fraction, and lung tissue injury in rabbits with smoke inhalation injury.

Methods: Sixteen adult New Zealand big ear rabbits were subjected to smoke inhalation injury and then were divided into pure injury group (PI, n = 8) and MSC transplantation group (MT, n = 8) according to the random number table. Via ear marginal vein, rabbits in PI group were injected with 10 mL phosphate buffered saline (PBS); rabbits in MT group were injected with 10 mL PBS containing the third passage MSC (1 x 10⁷ cell) isolated from marrow of healthy young New Zealand big ear rabbit. Another 8 rabbits were enrolled as normal control group (NC). Rabbits in NC group were injected with 10 mL PBS via ear marginal vein without smoke inhalation injury. Blood was harvested from rabbits in PI and MT groups at post injury hour (PIH) 2, 4, 6. Contents of TNF-α, IL-1β, IL-6, and IL-10 in serum were determined with ELISA. At PIH 24, left lung was harvested for morphology and histopathology observation; the right lung tissue was obtained to measure and calculate lung water mass fraction. Blood and lung tissue of rabbits in NC group were harvested and determined in the same way. Data were processed with t test.

Results: (1) Serum contents of TNF-α in PI and MT groups at each time point were obviously higher than that in NC group (t = 2.43 - 9.57, P < 0.05 or P < 0.01). Serum contents of IL-1β and IL-6 in PI group at each time point were obviously higher than those in NC group (t = 8.49 - 19.80, P values all below 0.01). Serum content of IL-1β in MT group at each time point was close to that in NC group (t = 0.11 - 0.92, P values all above 0.05). Serum content of IL-6 in MT group at PIH 2 was close to that in NC group (t = 2.12, P > 0.05), but that of MT group increased significantly at PIH 4 and 6 (t = 2.83, P values all below 0.05). Serum contents of TNF-α, IL-1β, and IL-6 in MT group at each time point were obviously lower than those in PI group (t = 2.35 - 12.45, P < 0.05 or P < 0.01). (2) Serum content of IL-10 in MT group at PIH 2, 4, and 6 was respectively (13.0 ± 3.6), (11.6 ± 8.5), (15.2 ± 4.4) pg/mL, and they were higher than those in PI group [(5.5 ± 3.4), (5.0 ± 1.7), (7.9 ± 3.5) pg/mL, with t value respectively 4.28, 2.15, 3.67, P values all below 0.01]. Serum contents of IL-10 in PI and MT groups were obviously higher than that in NC group (t = 2.46-8.14, P < 0.05 or P < 0.01). (3) Lung tissue injury in MT group was alleviated markedly as compared with that in PI group. (4) At PIH 24, lung water mass fraction in MT group was (69 ± 7)%, which was obviously lower than that in PI group [(87 ± 6)%, t = 5.49, P < 0.01]. Compared with that in NC group [(48 ± 3)%], lung water mass fraction in PI and MT groups were increased obviously (with t value respectively 16.93 and 7.22, P values all below 0.01).

Conclusions: MSC transplantation can decrease pro-inflammatory cytokines, increase anti-inflammatory cytokines, decrease lung water mass fraction, ameliorate systemic inflammatory response, and protect lung tissue in rabbits with smoke inhalation injury.