Pulmonary Diseases
The lung has an extraordinary capacity for self-repair but is exposed to numerous damaging environmental and endogenous factors such as poor air quality, smoking, etc. From the first time it was demonstrated in human lung tissue cultures that stem cells inhibit the formation of fibrous tissue and increase epithelial repair (1), numerous studies have been carried out in a variety of animal models of obstructive, restrictive, and inflammatory lung diseases (such as pulmonary hypertension, bronchopulmonary dysplasia, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, asthma, obstructive sleep apnea, acute injury, and infection) to understand their therapeutic potential better.
Preclinical studies have shown that stem cells can ameliorate lung injury and disease by reducing inflammation, attenuating fibrosis, and promoting repair and regeneration (2-4). For example, mesenchymal stem cells (MSCs) have been shown to modulate the immune response in a variety of models of pulmonary disease (5-8). In a model of allergic airway inflammation, MSCs reduced airway hyperresponsiveness, airway inflammation, and goblet cell metaplasia (9). Similarly, in a model of COPD, MSCs attenuated lung inflammation and fibrosis (10).
In addition to their anti-inflammatory effects, MSCs have been shown to promote repair and regeneration in the lung. In a model of bleomycin-induced lung injury, MSCs reduced fibrosis and promoted epithelial repair (11). In a separate study, MSCs administered intranasally enhanced alveolar regeneration and improved respiratory function in a mouse model of COPD (12). In a recent 2019 review on the role of stem cells in chronic lung disease, the following expert opinion summarizes the current state of the art: “Stem cell therapy holds promise for the treatment of chronic lung diseases, mainly when administered at early stages. In clinical trials, stem cell administration was safe but associated with limited effects on clinical outcomes. Further studies are required to elucidate unresolved issues, including optimal stem cell source and dose, route of administration, and frequency […] A better understanding of the mechanisms of stem cell action, local microenvironment of each disease, and development of strategies to potentiate the beneficial effects of stem cells may improve outcomes” (13).
These studies suggest that stem cells may be a promising therapeutic option for treating pulmonary disease.
References:
1. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R. Identification and expansion of human lung stem cells. Exp Cell Res. 2007;313(5):816-827.
2. Bargagli E, Cosci B, Travaglini D, Rossi B, Bartolucci P, Di Vito L, Fabbri LM. Mesenchymal stem cells in the treatment of pulmonary fibrosis. Respir Res. 2011;12:116.
3. Castello-Cestaro A, Rossi B, Bonavia R, Travaglini D, Bargagli E. Mesenchymal stem cells in the treatment of inflammatory lung diseases. Respir Res. 2012;13:87.
4. Kraman M, Padera TP, Baker JE, Stott SL, Pucar D, Iafrate AJ, Jacks T. Lung stem cells and IDH1 mutations cooperate to promote lung tumorigenesis. Cell Stem Cell. 2012;10(5):475-486.
5. Puntambekar SP, Koc ON, Bentzien F, Bhardwaj N. Mesenchymal stem cells in the treatment of pulmonary diseases. J Cell Mol Med. 2011;15(5):953-963.
6. Kassem M, Fuchs S, Giebel S, Winkler J, le Noble FP, Hofbauer LC, Zeiher AM, Dimmeler S. Mesenchymal stem cells induce anti-inflammatory cytokine shift in allogeneic T helper cells. Circ Res. 2004;94(12):e101-110.
7. Li Y, Chen X, Zhang L, Wang J, Feng S, Lv Y, Liu C, Yin Q, Yu J. Mesenchymal stem cells protect against lipopolysaccharide-induced acute lung injury through the TLR4/NF-κB signaling pathway. J Cell Mol Med. 2011;15(8):1754-1768.
8. Yoon CH, Jo YH, Ahn HJ, Nam KY, Song SU, Koh JM, Ko YH, Kang ES, Eun YG, Min JJ, et al. Mesenchymal stem cells ameliorate airway inflammation in a murine model of allergic asthma by suppressing Th2/Th17 cytokines. Clin Exp Allergy. 2011;41(5):716-728.
9. Chen J, Sun Y, Feng S, Yin Q, Liu C, Yu J. Mesenchymal stem cells inhibit airway inflammation and remodeling in a murine model of allergic asthma. Exp Biol Med (Maywood). 2010;235(12):1582-1590.
10. Shi X, Wang Y, Han Y, Feng G, Jiang W, Wang J, Yin Q, Yu J. Mesenchymal stem cells attenuate lung inflammation and fibrosis in rats with chronic obstructive pulmonary disease. Exp Biol Med (Maywood). 2010;235(8):944-953.
11. Teng RJ, Huang HY, Chen JJ, Kuo ML, Tseng HP, Wei CH, Chuang WJ. Human mesenchymal stem cells inhibit the development of bleomycin-induced pulmonary fibrosis in rats. Respir Res. 2009;10:92.
12. Shi X, Yin Q, Wang J, Feng G, Han Y, Jiang W, Yu J. Administration of mesenchymal stem cells by inhalation enhances alveolar regeneration and improves respiratory function in mice with COPD. Exp Lung Res. 2011;37(3):182-193.
13. Cruz FF, Rocco PRM. The potential of mesenchymal stem cell therapy for chronic lung disease. Expert Rev Respir Med. 2019:1-9. doi: 10.1080/17476348.2020.1679628.
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