Pulmonary fibrosis is a type of chronic, progressive, fibrotic lung disease of unclear cause with few treatment options. Cell therapy is emerging as a promising novel modality for facilitating lung repair. Mesenchymal stem cell (MSC)-based and macrophage-based cell therapies are regarded as promising strategies to promote lung repair, due to incredible regenerative potential and typical immunomodulatory function, respectively. Extracellular vesicles (EVs), including exosomes and microvesicles, are cell-derived lipid-bilayer membrane vesicles that are secreted from virtually every cell and are involved in intercellular communication by delivering expansive biological cargos to recipients. This review provides a deep insight into the recent research progress concerning the effects of MSC and macrophage-associated EVs on the pathogenesis of pulmonary fibrosis. In addition to discussing their respective vital roles, we summarize the importance of cross-talk, as macrophages are vital for MSCs to exert their protective effects through two major patterns, including attenuating macrophage activation and M1 phenotype macrophage polarization. Moreover, miRNAs are selectively enriched into EVs as essential components, and consideration is given to the particular effects of EV-associated miRNAs.

Background: Fibrotic diseases take a very heavy toll in terms of morbidity and mortality equal to or even greater than that caused by metastatic cancer. This meta-analysis aimed to evaluate the effect of endothelin receptor antagonists on idiopathic pulmonary fibrosis. Method: A systematic search of the clinical trials from the Medline, Google Scholar, Cochrane Library, and PubMed electronic databases was performed. Stata version 12.0 statistical software (Stata Crop LP, College Station, TX) was adopted as statistical software. Result: A total of 5 studies, which included 1500 participants. Our analysis found there is no significant difference between using the endothelin receptor antagonists’ group and placebo groups regarding the lung function via estimating both the change of forced vital capacity from baseline and DLco index. Exercise capacity and serious adverse effects are taken into consideration as well; however, there is still no significant change between the 2 groups. Conclusion: This meta-analysis provides insufficient evidence to support that endothelin receptor antagonists’ administration provides a benefit among included participants who encounter idiopathic pulmonary fibrosis.

Ischemic stroke represent major global health challenges due to their high incidence and debilitating consequences. Similarly, lung ischemia-reperfusion injury has gained increasing attention in the medical research community. The emerging concept of the lung-brain axis has shed new light on the complex interplay between these two organ systems during pathological injury, demonstrating that their interaction can significantly exacerbate ischemia- reperfusion damage. Although these conditions exhibit distinct pathophysiological characteristics, they share remarkable similarities in their genetic responses to tissue injury. Recent advancements in regenerative medicine have highlighted the therapeutic potential of mesenchymal stem cells (MSCs) in addressing both ischemic stroke and lung ischemia-reperfusion injury. Particularly, extracellular vesicles (EVs) derived from MSCs have emerged as a promising therapeutic avenue. These MSC-derived EVs exert their protective effects through multiple mechanisms, including immunomodulation, anti-inflammatory actions, anti-apoptotic effects, oxidative stress regulation, and promotion of angiogenesis. This comprehensive review aims to systematically examine the therapeutic roles of MSC-derived EVs in both cerebral and pulmonary ischemia-reperfusion injuries, while emphasizing their shared pathological mechanisms. By elucidating these common pathways, we hope to provide novel perspectives and research directions for both clinical and basic investigations into lung-brain ischemia-reperfusion injury.