Stem Cell Therapy for Asthma

Asthma is a chronic inflammatory disease of the airways caused by endogenous (such as chronic inflammation and oxidative stress) and exogenous factors (such as exposure to CS and air pollution), involving multiple cells and cellular components.

In this condition, effector cells secrete inflammatory factors that cause inflammation, mediate peripheral tissue destruction, induce high secretion of airway mucus, hypertrophy of smooth muscle, and increase of goblet cells. 

Mesenchymal stem cells (MSCs) have a great potential to proliferate, undergo multidirectional differentiation, and exert immunoregulatory effects. They can regulate cell proliferation and control the secretion of various immune cells through cell-cell contact.

MSCs can secrete a variety of growth factors to promote the repair of alveolar epithelial cells and pulmonary vascular endothelial cells. 

Animal studies have shown that MSCs can revert pathological chances and intratracheal inflammation. They have also shown the reduction of pathological changes, such as basement membrane epithelial thickness, subepithelial smooth muscle thickness, and increase of goblet cell number, to reduce airway inflammation. 

How do Stem Cells Work? 

Lung lesions can trigger the release of various chemokines, which can induce the migration and colonization of vascular MSCs towards the damaged sites and then exert an immunomodulatory effect and improve asthma symptoms.

Transforming growth factor-beta 1 (TGF-β1) is a multifunctional cytokine that plays a critical role in cell growth/differentiation and immune regulation. It can recruit MSCs to participate in tissue repair and remodeling at injured sites.

The excessive production of helper T lymphocyte type 2 (Th2) and Th17 cytokines promotes the eosinophil- and neutrophil-mediated airway inflammation, respectively, and excessive maturation of dendritic cells (DC) can further activate Th2 cells.

Many studies have proved that MSCs exert their therapeutic effect on asthma by restoring Th1/Th2 balance. They also help inhibit the excessive maturation and increase of dendritic cells.

Conclusions

Currently, corticosteroids and long-acting β-agonists are the main drugs for asthma therapy. But for refractory asthma and steroid-resistant neutrophilic asthma, drugs can’t control the asthma symptom well.

Multiple studies have shown that MSCs can be an effective therapy for respiratory diseases like asthma by modulating the chronic inflammatory response. Clinical trials have already shown promising results in patients with COPD and acute respiratory distress syndrome (ARDS). There are currently many ongoing clinical trials in humans with asthma to evaluate their efficacy. 

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Sources:

Wang MY, Zhou TY, Zhang ZD, Liu HY, Zheng ZY, Xie HQ. Current therapeutic strategies for respiratory diseases using mesenchymal stem cells. MedComm (2020). 2021 Sep 2;2(3):351-380. doi: 10.1002/mco2.74. PMID: 34766151; PMCID: PMC8554668. 

Yu X, Yu L, Guo B, Chen R, Qiu C. A narrative review of research advances in mesenchymal stem cell therapy for asthma. Ann Transl Med. 2020 Nov;8(21):1461. doi: 10.21037/atm-20-6389. PMID: 33313206; PMCID: PMC7723541. 

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