Mesenchymal stem cells modulate lung injury

Abstract

Mesenchymal stem cells (MSCs) have been shown to differentiate into a variety of mesenchymal cell types, including fibroblasts, myofibroblasts, osteoblasts, chondroblasts, adipocytes, and myoblasts, as well as epithelial cells. It has been shown that these cells can be recovered from bone marrow as well as umbilical cord blood, and they can be propagated, stored, and administered to animals and patients in clinical trials. It is clear that the cells engraft in the lung, and several laboratories have demonstrated an ameliorating effect in models of acute injury caused by LPS and in chronic lung injury induced by bleomycin and asbestos. However, it is not at all clear under what conditions these cells must be applied to provide an advantage and when using these cells might cause exacerbation of the lung injury. This brief review focuses on the biology of MSCs in vitro, how the cells have been used in some animal models, and the potential for their use in therapeutic strategies for diseases as diverse as lung cancer and interstitial fibrosis.

Figure 1.

A and B show asbestos-induced fibroproliferative lesions that have developed at the bronchiolar-alveolar duct junctions in the lungs of rats exposed for 3 hours (see References 12–18 for details). Green fluorescent protein (GFP) labels the mesenchymal stem cells that were used for the bone marrow transplant in these animals and that migrated to the developing lesions. The same lesion is shown in B stained positively with K19, suggesting that several of the GFP-labeled cells in A have differentiated to cells with epithelial characteristics. (Original magnification: ×20.)

Figure 2.

Activated bone marrow–derived mesenchymal stem cells (BMSC) conditioned media (CM) induces COL1A1 expression in 16Lu fibroblasts. Quiescent BMSC ( 8 × 1 0⁵ cells) were cultured in 20 ml serum-free (SF) medium. After 48 hours the mesenchymal stem cell CM was concentrated 5-fold. Quiescent 16Lu fibroblasts were cultured for 48 hours in SF medium, TGF-β₁ (5 ng/ml, positive control) or serially diluted acid-activated or latent CM. COL1A1 up-regulation was determined by quantitative real-time RT-PCR. Data represent the mean ± SEM from triplicate wells for each treatment group. Significantly different from SF: *P < 0.05, **P < 0.002.