Mesenchymal Stem Cells and Airway Problems: Current Approaches and Future Perspectives
Development of cell therapies and bioengineering approaches for lung diseases has rapidly progressed over the past decade (Weiss 2014). A number of early reports initially suggested that bone marrow-derived cells, including MSC and other populations, could structurally engraft as mature differentiated airway and alveolar epithelial cells or as pulmonary vascular or interstitial cells (Kassmer and Krause 2010). Some recent reports continue to suggest that engraftment of the donor-derived airway can occur with several different types of bone marrow-derived cells (Wong et al. 2009).
MSC from bone marrow, adipose and placental tissue, and other origins have been widely investigated for their immunomodulatory effects in a broad range of inflammatory and immune diseases (Keating 2012). However, the mechanisms of MSC actions are only partially understood. In addition to the paracrine actions of soluble peptide and other mediators, a growing body of data suggests that release of episomal or microsomal particles by MSC can influence the behavior of both surrounding structural and inflammatory cells (Weiss 2014). A recent report suggests that MSC may also promote repair by activation of endogenous distal lung airway progenitor cell populations in mouse models (Tropea et al. 2012). Administration of MSC of either bone marrow or placental origin has also been demonstrated to decrease injury and inflammation in endotoxin or bacterially injured human lung explants (Lee et al. 2013).
MSC can also exert effects on lung inflammation and injury through primary interactions with the immune system rather than through direct actions in lung, in particular when the cells are systemically delivered (Weiss 2014).
In the light of more recent findings, chronic persistent lung diseases with low level or smoldering inflammation-such as chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis-may not represent the best therapeutic targets for MSC intervention. On the contrary, more acute inflammatory lung or systemic diseases such as adult respiratory distress syndrome or sepsis/septic shock may be better targets (Bishop et al. 2012). Consequently, the scenario of an acute postresectional BPF, where the acute inflammation component is prominent along with infection, may represent an ideal target for MSC clinical use in thoracic surgery.
The use of autologous MSC eliminates the patient’s need for lifelong immunosuppressant therapy and avoids the risk of infection. Bone marrow remains one of the best sites for MSC harvesting, although even adipose tissue is a viable option and may be further explored in the future.
There may be some concern that MSC may have an undesirable effect on tumor growth, but the in vivo evidence collected so far remains inconclusive. A recent clinical study in which autologous BMMSC from cancer patients was locally administered at the site of malignant primary bone tumor resection showed no increase in the cancer local recurrence risk in patients treated with the cell-based therapy after an average follow-up of 15 years (Hernigou et al. 2014).