title: Concise Review: The Bystander Effect: Mesenchymal Stem Cell-Mediated Lung Repair.
abstract: Mesenchymal stem or stromal cells (MSCs), a heterogeneous subset of adult stem/progenitor cells, have surfaced as potential therapeutic units with significant clinical benefit for a wide spectrum of disease conditions, including those affecting the lung. Although MSCs carry both self-renewal and multilineage differentiation abilities, current dogma holds that MSCs mainly contribute to tissue regeneration and repair by modulating the host tissue via secreted cues. Thus, the therapeutic benefit of MSCs is thought to derive from so called bystander effects. The regenerative mechanisms employed by MSCs in the lung include modulation of the immune system as well as promotion of epithelial and endothelial repair. Apart from secreted factors, a number of recent findings suggest that MSCs engage in mitochondrial transfer and shedding of membrane vesicles as a means to enhance tissue repair following injury. Furthermore, it is becoming increasingly clear that MSCs are an integral component of epithelial lung stem cell niches. As such, MSCs play an important role in coupling information from the environment to stem and progenitor populations, such that homeostasis can be ensured even in the face of injury. It is the aim of this review to outline the major mechanisms by which MSCs contribute to lung regeneration, synthesizing recent preclinical findings with data from clinical trials and potential for future therapy. Stem Cells 2016;34:1437-1444.
authors.affiliation: Department of Experimental Medical Science, Lung Biology Unit, Lund University, Lund, Sweden.
authors.forename: Ulrika Blank
authors.initials: UB
authors.lastname: Savukinas
authors.affiliation: Department of Experimental Medical Science, Lung Biology Unit, Lund University, Lund, Sweden.
authors.forename: Sara Rolandsson
authors.initials: SR
authors.lastname: Enes
authors.affiliation: Department of Experimental Medical Science, Lung Biology Unit, Lund University, Lund, Sweden.
authors.forename: Annika Andersson
authors.initials: AA
authors.lastname: Sjöland
authors.affiliation: Department of Experimental Medical Science, Lung Biology Unit, Lund University, Lund, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Westergren-Thorsson
mesh_terms: D024201:Bystander Effect; D002986:Clinical Trials as Topic; D006801:Humans; D008168:Lung / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D019899:Paracrine Communication; D012038:Regeneration
keywords: Immunomodulation; Lung; Mesenchymal stem cell; Paracrine communication; Regenerative medicine; Stem cell niche