MSCs: The Other Facts
In contrast to the idea that the key function of hMSCs is to supply replacement parts for mesenchymal tissue are the observations that human marrow-derived MSCs can be activated to secrete cytokines/growth factors which inhibit an in vitro mixed lymphocyte assay (Abboud et al., 1987; Maitra et al., 2004). These observations suggested that hMSCs could be used therapeutically as allogeneic, “universal cells.” To support this suggestion, it has been further documented that culture-expanded hMSCs do not have MHC class I cell surface markers, but rather only MHC class II and no co-stimulator molecules (Dominici et al., 2006). Thus, hMSCs cannot be antigen-presenting cells and should be invisible to the host’s immune system. It is important to note that in all of the clinical usages of human adult marrow-derived, culture-expanded MSCs, whether autologous or allogeneic, no adverse events have been recorded (Abdallah et al., 2007; Le Blanc et al., 2007). This establishes that the procedures for isolation and culture expansion are safe and that in certain clinical applications, there has been a benefit from the intravenous delivery of hMSCs.
hMSCs can be of great value by virtue of their ability to differentiate into distinctive and specialized cells and their secretion of site-specific proteins. Defining the mechanisms of MSC therapeutic efficacy may require elaborate technology associated with delivery, imaging, and targeting, which has the potential of identifying appropriate delivery mechanisms and the ability to localize hMSCs (Caplan et al., 2007). The use of hMSCs in interstitial pulmonary fibrosis, cardiovascular disease, and neurological disorders is currently being explored and was based upon not only the ability of hMSCs to be site-specific producers of trophic factors, but also upon their ability to induce host tissue trophic factors which may also contribute to the inflammatory milieu (Dai et al., 2005; Stripp et al., 2006). It remains to be determined if hMSCs home to the site of inflammation and/or if the MSCs’ destination is a central or systemic site such as the lymph system. Caplan and his colleagues have recently described a cell targeting technology for such site-directed therapeutics (Dennis et al., 2004). The issue is where to target the therapeutic cell for the most impact and largest clinical response. Targeting will depend upon the clinical entity in question and the stage and severity of the disease. The studies outlined in this review focus on lung airway inflammation and remodeling and the therapeutic potential of hMSCs.