Lung-resident mesenchymal stromal cells are tissue-specific regulators of lung homeostasis

Until recently, data supporting the tissue-resident status of mesenchymal stromal cells (MSC) has been ambiguous since their discovery in the 1950–60s. These progenitor cells were first discovered as bone marrow-derived adult multipotent cells and believed to migrate to sites of injury, opposing the notion that they are residents of all tissue types. In recent years, however, it has been demonstrated that MSC can be found in all tissues and MSC from different tissues represent distinct populations with differential protein expression unique to each tissue type. Importantly, these cells are efficient mediators of tissue repair, regeneration, and prove to be targets for therapeutics, demonstrated by clinical trials ( phase 1– 4) for MSC-derived therapies for diseases like graft-versus-host-disease, multiple sclerosis, rheumatoid arthritis, and Crohn’s disease. The tissue-resident status of MSC found in the lung is a key feature of their importance in the context of disease and injuries of the respiratory system, since these cells could be instrumental to providing more specific and targeted therapies. Currently, bone marrow-derived MSC have been established in the treatment of disease, including diseases of the lung. However, with lung-resident MSC representing a unique population with a different phenotypic and gene expression pattern than MSC derived from other tissues, their role in remediating lung inflammation and injury could provide enhanced efficacy over bone marrow-derived MSC methods. Through this review, lung-resident MSC will be characterized, using previously published data, by surface markers, gene expression patterns, and compared with bone-marrow MSC to highlight similarities and, importantly, differences in these cell types.