Combined treatment with bone marrow mesenchymal stem cells and methylprednisolone in paraquat-induced acute lung injury.

BACKGROUND: To evaluate the efficacy of combined treatment with bone marrow mesenchymal stem cell (BMSC) transplantation and methylprednisolone (MP) to treat paraquat (PQ)-induced acute lung injury. MATERIALS AND METHODS: A total of 102 female rats were randomly divided into five groups: PQ, BMSC, MP, BMSC + MP and normal control. After 14 days of PQ poisoning, the survival of rats, wet/dry weight ratio of lung tissue, serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-10, malondialdehyde (MDA) and superoxidase dismutase (SOD), and the expression of nuclear factor (NF)-кB p65 in lung tissue were determined. RESULTS: Rats in BMSC and BMSC + MP groups survived. BMSC transplantation significantly decreased the wet/dry weight ratio of lung tissue, down-regulated NF-кB p65 expression in lung tissue, lowered serum levels of TNF-α, IL-1ß, IL-6 and MDA, and increased serum levels of IL-10 and SOD. These changes were particularly significant on days 7-14 after PQ poisoning. The above changes were more significant in the MP group on days 1-3 after PQ poisoning, compared with those of the BMSC group. However, the BMSC + MP group showed more significant changes on days 1-14 after PQ poisoning than those of both BMSC and MP groups. CONCLUSIONS: MP inhibits the inflammatory response, reduces the products of lipid peroxidation and promotes survival of transplanted BMSC, thus improving the intermediate and longer term efficacy of BMSC transplantation for treatment of PQ-induced lung injury.

Optimal conditions of bone marrow mesenchymal stem cells on paraquat-induced acute lung injury in rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect of bone marrow mesenchymal stem cell (BMSC) transplantation on acute lung injury induced by paraquat (PQ) poisoning in rats, and to identify the optimal transplantation conditions.</p><p><b>METHODS</b>Two hundred female rats were randomly divided into six groups, i.e., PQ group (n = 15), BMSC treatment group 1 (n = 15 for each subgroup), BMSC treatment group 2 (n = 15 for each subgroup), BMSC control group 1 (n = 15 for each subgroup), BMSC control group 2 (n = 15), and normal control group (n = 5). In the PQ group, each rat was intraperitoneally injected with 20% PQ solution (15 mg/kg). In BMSC treatment group 1, each rat was injected via the caudal vein with 1×10(5), 10(6), 10(7)or 10(8) BMSCs (1 ml) after 6 hours of PQ exposure. In BMSC treatment group 2, each rat was injected via the caudal vein with 1×10(7) BMSCs (1 ml) after 1, 6, 12, or 24 hours of PQ exposure. In BMSC control group 1, each rat was injected via the caudal vein with 1×10(5), 10(6), 10(7), or 10(8) BMSCs (1 ml). In BMSC control group 2, each rat was injected via the caudal vein with 1×10(7) BMSCs (1 ml). In the normal control group, each rat was intraperitoneally injected with an equal volume of 0.9% saline. The lung wet/dry weight ratio and plasma tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) levels were measured at 1, 3, and 7 days after various treatments.</p><p><b>RESULTS</b>Compared with the normal control group, the PQ group showed significantly higher lung wet/dry weight ratios at 3 and 7 days after PQ exposure and significantly higher plasma TNF-α and MDA levels at 1, 3, and 7 days after PQ exposure (P < 0.01). Compared with the PQ group, BMSC treatment group 1 showed significantly lower lung wet/dry weight ratios at 7 days after injection of 1×10(6) and 10(7) BMSCs, significantly lower plasma TNF-α levels at 3 and 7 days after injection of 1×10(5), 10(6), and 10(7) BMSCs, and significantly lower plasma MDA levels at 3 days after injection of 1×10(6) and 10(7) BMSCs and at 7 days after injection of 1×10(5), 10(6), and 10(7) BMSCs (P < 0.05 or P < 0.01). Compared with the PQ group, BMSC treatment group 2 showed significantly lower lung wet/dry weight ratios at 7 days after injection of BMSCs following 1, 6, and 12 hours of PQ exposure, significantly lower plasma TNF-α levels at 3 and 7 days after injection of BMSCs following 1, 6, and 12 hours of PQ exposure, and significantly lower plasma MDA levels at 3 days after injection of BMSCs following 6 hours of PQ exposure and at 7 days after injection of BMSCs following 1, 6, and 12 hours of PQ exposure (P < 0.01).</p><p><b>CONCLUSION</b>BMSCs have a protective effect on the lung in rats with PQ poisoning, and the effect is closely related to the transplantation time and number of transplanted BMSCs. After 6 hours of PQ exposure, intravenous injection of 1×10(7) BMSCs can result in significant decreases in lung wet/dry weight ratio and plasma TNF-α and MDA levels.</p>

Protection of bone marrow mesenchymal stem cells from acute lung injury induced by paraquat poisoning.

OBJECTIVE. To examine the protective effect of bone marrow mesenchymal stem cell (BMSC) transplantation against lung injury induced by paraquat (PQ) poisoning. MATERIALS AND METHODS. Fifty-four female SD rats were randomly divided into four groups: a PQ group, a BMSC treatment group, a BMSC control group, and a normal control group. BMSC, isolated and cultured in vitro, were injected into the tail veins of the rats. The mortality rate, the ratio of lung wet/dry weight, plasma levels of IL-1ß, tumor necrosis factor-α (TNF-α), malonaldehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-P(X)), and NF-κBp65 expression in the lung tissues were examined during 14 days after injection. Results. Survival in the PQ group ranged from 8 to 12 days, with an average of 9.6 days. All the rats in the BMSC treatment group survived for more than 14 days. In the BMSC treatment group, the ratio of lung wet /dry weight (P  =  0.02  <  0.05), plasma IL-1ß and TNF-α levels (P  =  0.00  <  0.01), MDA levels (P  = 0.03  <  0.05), and expression of NF-κBp65 in the lung tissues (P  =  0.00  <  0.01) were significantly lower than those in the PQ group by day 7 post-injection. However, the SOD and GSH-P(X) levels began to increase (P  =  0.00  < 0.01) compared with the PQ group. There was no significant difference between the BMSC control group and the normal control group (P  >  0.01). DISCUSSION AND CONCLUSION. BMSC transplantation may have the potential to protect against PQ-induced lung injury, by reducing lung edema and lipid peroxidation, inhibiting the release of inflammatory mediators. However, the protective effects require time to develop, and early BMSC transplantation may be more evident during the middle and late stages of therapy.