The Regenerative Power of Stem Cells: Treating Bleomycin-Induced Lung Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with no known cure, characterized by the formation of scar tissue in the lungs, leading to respiratory failure. Although the exact cause of IPF remains unclear, the condition is thought to result from a combination of genetic and environmental factors. One of the most widely used animal models to study IPF is the bleomycin-induced lung injury model in mice. In this model, the administration of the chemotherapeutic agent bleomycin causes pulmonary inflammation and fibrosis, which closely mimics the pathological features of human IPF. Numerous recent investigations have explored the functions of various categories of stem cells in the healing process of lung injury induced by bleomycin in mice, documenting the beneficial effects and challenges of this approach. Differentiation of stem cells into various cell types and their ability to modulate tissue microenvironment is an emerging aspect of the regenerative therapies. This review article aims to provide a comprehensive overview of the role of stem cells in repairing bleomycin-induced lung injury. It delves into the mechanisms through which various types of stem cells, including mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, and lung resident stem cells, exert their therapeutic effects in this specific model. We have also discussed the unique set of intermediate markers and signaling factors that can influence the proliferation and differentiation of alveolar epithelial cells both during lung repair and homeostasis. Finally, we highlight the challenges and opportunities associated with translating stem cell therapy to the clinic for IPF patients. The novelty and implications of this review extend beyond the understanding of the potential of stem cells in treating IPF to the broader field of regenerative medicine. We believe that the review paves the way for further advancements in stem cell therapies, offering hope for patients suffering from this debilitating and currently incurable disease.

Airway basal cell‑derived exosomes suppress epithelial‑mesenchymal transition of lung cells by inhibiting the expression of ANO1

“…Bleomycin-induced pulmonary fibrosis is a widely used model, which closely mimics the pathological features of human IPF. 9-days treatment of bleomycin initiates the fibrotic response, resulting in the expression of pro-fibrotic factors ( 40 ), followed by the deposition of collagen ( 41 ). The in vivo assay of the present study indicated that exosome treatment effectively inhibited bleomycin-induced pulmonary fibrosis, consistent with in vitro results.…”

Unlocking the Future: Pluripotent Stem Cell-Based Lung Repair

“…While all compounds seem to induce fibrosis via AT2 cells, none of the models addresses genetic causes of familial and idiopathic fibrosis. Thus, recent models were not able to directly investigate the effect of engrafted gene-corrected or WT iPSC derivatives on fibrosis caused by the mutated endogenous AT2 cells [114].…”

Molecular Mechanisms Responsible for the Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Lung Fibrosis

“…Results recently obtained in large number of experimental studies indicated that mesenchymal stem cells (MSCs), self-renewable, adult, rapidly proliferative, multipotent cells, should be considered as potentially new therapeutic agents for the treatment of lung fibrosis [18][19][20][21]. MSCs produce various anti-inflammatory and immunosuppressive factors which may suppress immune cell-driven lung injury and inflammation, attenuate collagen production, inhibit epithelial to mesenchymal transition (EMT) and prevent tissue remodeling in the fibrotic lungs [20][21][22]. MSCs release hepatocyte growth factor (HGF) which binds to c-Met receptor on activated fibroblasts, inducing activation of the PI3K/Akt and Ras/MAPK pathways, which lead to the inhibition of fibroblast activation and the subsequent reduction in collagen synthesis [23].…”

“…Since MSC-dependent beneficial effects in the treatment of lung fibrosis are mainly reliant on the biological activity of MSC-derived anti-fibrotic, immunoregulatory and angio-modulatory factors, injection of MSC-derived secretome is considered to be a novel approach for the treatment of pulmonary fibrosis, which may overcome all potential safety issues associated with the transplantation of MSCs [20]. The majority of MSC-sourced bioactive factors are contained within MSC-derived exosomes (MSC-Exos), nano-sized extracellular vesicles (EVs) which are abundantly present in the MSC-sourced secretome [28].…”