Comparative study of adipose tissue derived mesenchymal stem cells with rapamycin on paraquat-induced acute lung injury and pulmonary fibrosis in a mouse model: histological and biochemical study.

Background: The most noticeable consequence of paraquat (PQ) toxicity is pulmonary fibrosis. Mesenchymal stem cells have the remarkable ability to self-renew and differentiate into many cell types. One such type is adipose tissue-derived Mesenchymal Stem Cells (AT-MSCs), which are derived from adipose tissue. Thus, the purpose of this study was to compare the effects of AT-MSCs and rapamycin on paraquat-induced acute lung injury and pulmonary fibrosis in a mouse model.

Methods: Fifty female mice were randomly allocated to four groups. Group I (control group) received the drug solvent using the same route of administration for the same duration as the corresponding experimental groups. Group II (pulmonary fibrosis group) lung injury was induced by injection of PQ at a dosage of 40 mg/kg. Group III (AT-MSCs group) received 1.0 × 10⁵ cells/mouse of male AT-MSCs. Group IV (rapamycin group) received 2.5 mg/kg/day diluted in 1% Dimethyl sulfoxide orally for two weeks. Lung tissue was harvested at the end of the experiment and analyzed by light and electron microscopy in addition to immunohistochemistry evaluation of p53. Samples were also taken to -80 for identification of the Y chromosome (SRY gene) and biochemical testing in the lung tissue. The injured lung was improved with AT-MSCs. Just like the control group, they restored p53 levels.

Results: Following injection with AT-MSCs, there was an increase in Y-chromosome expression levels. Treatment with AT-MSCs also reduced malondialdehyde levels in the lung tissues while increasing superoxide dismutase and reduced glutathione levels. The results showed that pulmonary fibrosis may be mitigated following AT-MSCs transplantation in PQ-poisoned mice by suppressing the synthesis of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-alpha) in the lung tissues of the animals. The SRY gene's expression was significantly upregulated in the AT-MSCs treatment group.

Conclusion: This study provides more evidence that the immunomodulatory effects of AT-MSC transplantation can alleviate pulmonary inflammatory and fibrotic alterations more effectively than rapamycin. As a result, these cells are a very promising pharmacological therapy for acute lung injury and pulmonary fibrosis induced by PQ poisoning.