title: Airway delivery of soluble factors from plastic-adherent bone marrow cells prevents murine asthma.
abstract: Asthma affects an estimated 300 million people worldwide and accounts for 1 of 250 deaths and 15 million disability-adjusted life years lost annually. Plastic-adherent bone marrow-derived cell (BMC) administration holds therapeutic promise in regenerative medicine. However, given the low cell engraftment in target organs, including the lung, cell replacement cannot solely account for the reported therapeutic benefits. This suggests that BMCs may act by secreting soluble factors. BMCs also possess antiinflammatory and immunomodulatory properties and may therefore be beneficial for asthma. Our objective was to investigate the therapeutic potential of BMC-secreted factors in murine asthma. In a model of acute and chronic asthma, intranasal instillation of BMC conditioned medium (CdM) prevented airway hyperresponsiveness (AHR) and inflammation. In the chronic asthma model, CdM prevented airway smooth muscle thickening and peribronchial inflammation while restoring blunted salbutamol-induced bronchodilation. CdM reduced lung levels of the T(H)2 inflammatory cytokines IL-4 and IL-13 and increased levels of IL-10. CdM up-regulated an IL-10-induced and IL-10-secreting subset of T regulatory lymphocytes and promoted IL-10 expression by lung macrophages. Adiponectin (APN), an antiinflammatory adipokine found in CdM, prevented AHR, airway smooth muscle thickening, and peribronchial inflammation, whereas the effect of CdM in which APN was neutralized or from APN knock-out mice was attenuated compared with wild-type CdM. Our study provides evidence that BMC-derived soluble factors prevent murine asthma and suggests APN as one of the protective factors. Further identification of BMC-derived factors may hold promise for novel approaches in the treatment of asthma.
authors: University of Alberta, HMRC 407, Edmonton, AB, Canada.
authors: Lavinia I
authors: LI
authors: Ionescu
authors: Rajesh S
authors: RS
authors: Alphonse
authors: Narcy
authors: N
authors: Arizmendi
authors: Beverly
authors: B
authors: Morgan
authors: Melanie
authors: M
authors: Abel
authors: Farah
authors: F
authors: Eaton
authors: Marek
authors: M
authors: Duszyk
authors: Harissios
authors: H
authors: Vliagoftis
authors: Tamar R
authors: TR
authors: Aprahamian
authors: Kenneth
authors: K
authors: Walsh
authors: Bernard
authors: B
authors: Thébaud
mesh_terms: D000818:Animals; D001249:Asthma / Q000473:pathology / Q000517:prevention & control*; D001854:Bone Marrow Cells / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C