Mesenchymal stromal cell-based therapy in lung diseases; from research to clinic

Abstract

Recent studies demonstrated that mesenchymal stem cells (MSCs) are important for the cell-based therapy of diseased or injured lung due to their immunomodulatory and regenerative properties as well as limited side effects in experimental animal models. Preclinical studies have shown that MSCs have also a remarkable effect on the immune cells, which play major roles in the pathogenesis of multiple lung diseases, by modulating their activity, proliferation, and functions. In addition, MSCs can inhibit both the infiltrated immune cells and detrimental immune responses in the lung and can be used in treating lung diseases caused by a virus infection such as Tuberculosis and SARS-COV-2. Moreover, MSCs are a source for alveolar epithelial cells such as type 2 (AT2) cells. These MSC-derived functional AT2-like cells can be used to treat and diminish serious lung disorders, including acute lung injury, asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis in animal models. As an alternative MSC-based therapy, extracellular vesicles that are derived from MSC-derived can be employed in regenerative medicine. Herein, we discussed the key research findings from recent clinical and preclinical studies on the functions of MSCs in treating some common and well-studied lung diseases. We also discussed the mechanisms underlying MSC-based therapy of well-studied lung diseases, and the recent employment of MSCs in both the attenuation of lung injury/inflammation and promotion of the regeneration of lung alveolar cells after injury. Finally, we described the role of MSC-based therapy in treating major pulmonary diseases such as pneumonia, COPD, asthma, and idiopathic pulmonary fibrosis (IPF).

Keywords: ARDS; IPF; Mesenchymal stromal cell; asthma; lung; pneumonia.

Figure 1

Summary of the major functions of MSCs in key lung diseases and disorders. A. MSC treatment for asthma can increase TGF-beta and IL-10, but decrease the cytokines IL-4, IL-5 and IL-13. B. ARDS treatment with MSCs can lead to the increase of IL-4, IL-5, and IL-10, but decreases TNF-alpha, IL-1, and IL-6. C. MSC treatment for the IPF leads to the reduction of the deposition of collagen, activated fibroblasts, and pro-inflammatory cytokines. D. COPD treatment with MSCs can lead to a reduction in the TNF-alpha, IL-8 and inflammatory response, as well as the alleviation of emphysema.