• Du Jun, Chrystelle Garat, James West, Nathalie Thorn, Kelsey Chow, Timothy Cleaver, Timothy Sullivan, Enrique C Torchia, Christine Childs, Theodore Shade, Mehrdad Tadjali, Abigail Lara, Eva Nozik-Grayck, Stephen Malkoski, Brian Sorrentino, Barbara Meyrick, Dwight Klemm, Mauricio Rojas, David H Wagner, and Susan M Majka.
• Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology Program, University of Colorado Denver, Aurora, Colorado 80045, USA.
• Stem Cells. 2011 Apr 1;29(4):725-35.

AbstractTissue-resident mesenchymal stem cells (MSCs) are important regulators of tissue repair or regeneration, fibrosis, inflammation, angiogenesis, and tumor formation. Here, we define a population of resident lung MSCs (luMSCs) that function to regulate the severity of bleomycin injury via modulation of the T-cell response. Bleomycin-induced loss of these endogenous luMSCs and elicited fibrosis (pulmonary fibrosis), inflammation, and pulmonary arterial hypertension (PAH). Replacement of resident stem cells by administration of isolated luMSCs attenuated the bleomycin-associated pathology and mitigated the development of PAH. In addition, luMSC modulated a decrease in numbers of lymphocytes and granulocytes in bronchoalveolar fluid and demonstrated an inhibition of effector T-cell proliferation in vitro. Global gene expression analysis indicated that the luMSCs are a unique stromal population differing from lung fibroblasts in terms of proinflammatory mediators and profibrotic pathways. Our results demonstrate that luMSCs function to protect lung integrity after injury; however, when endogenous MSCs are lost, this function is compromised illustrating the importance of this novel population during lung injury. The definition of this population in vivo in both murine and human pulmonary tissue facilitates the development of a therapeutic strategy directed at the rescue of endogenous cells to facilitate lung repair during injury.Copyright © 2011 AlphaMed Press.

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