Deleterious Effects of Cigarette Smoke on the Properties and Functions of Mesenchymal Stem Cells

Katelyn Maloney

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Maloney, Katelyn
Faculty / Advisor: Zhang, Qunzhou, Le, Anh, D.
University of Pennsylvania School of Dental Medicine, Department of Oral & Maxillofacial Surgery/Pharmacology

Introduction

Cigarette Smoke (CS) contains a myriad of carcinogens and toxicants that contribute to the pathogenesis of chronic pulmonary diseases such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. These chemicals induce inflammatory reactions, alter immune responses and impair stem cell functions. Mesenchymal stem cells (MSC) represent a unique subpopulation of postnatal and non-haematopoietic stem cells that exist in almost all body tissues, such as bone marrow, adipose tissue, placental tissue, and umbilical cord, etc. They can differentiate into mesodermal lineages such as osteoblasts, chondrocytes, and adipocytes, and possess potent immunomodulatory and anti-inflammatory functions. These unique properties and functions of MSCs make them a promising source of cells for cell-based regenerative therapy of a wide spectrum of diseases, such as skin, skeletal, pulmonary, cardiovascular, and neurodegenerative diseases.

Methods

This review and presentation focus on the deleterious effects of CS on the properties and functions of endogenous MSCs and their potential contribution to the development of chronic lung diseases, particularly, COPD and pulmonary fibrosis. To this purpose, we conducted searches through the PubMed database. Articles were excluded if not in English. Articles that only focused on electronic cigarettes, hematopoietic stem cells, neural/progenitor stem cells, muscle stem cells/satellite cells, skin stem cells, and intestinal stem cells were excluded.

Results

In COPD, CS has been shown to alter the expression of MSC surface molecules, impair their multipotent differentiation and immunomodulatory capabilities, reduce their secretion of growth factors, chemokines and chemotactic factors. On the other hand, CS can compromise the ability of the body to regulate components of the adaptive immune system. In pulmonary fibrosis, dysregulation of pulmonary mesenchymal progenitor cells may lead to impairment of angiogenesis, microvasculature and exacerbate bleomycin-induced fibrosis. This dysregulation can promote excessive extracellular matrix deposition and lung scarring seen in pulmonary fibrosis.

Conclusion

Yet, despite the negative effects of CS on stem cell property and function, MSC-based therapy is emerging as a possible route for the treatment of pulmonary diseases. Ongoing preclinical and clinical studies have provided a promising evidence that stem cell-based therapy can reverse or halt the progression of the deleterious effects of CS on different tissues and organs of the body. Meta-analyses of COPD and pulmonary fibrosis have shown that MSC therapy leads to attenuation of acute lung injury, promoting lung repair, and improving lung function, thus highlighting the potential application of MSC-based therapy for these diseases.