Original pre-clinical scienceAttenuation of early airway obstruction by mesenchymal stem cells in a murine model of heterotopic tracheal transplantation
Section snippets
Animal maintenance
Experiments were conducted using 10- to 14-week-old female C57BL/6, BALB/c and CH3 mice (Jackson Laboratories, Bar Harbor, ME). The animals were housed in cages and maintained on a 12/12-hour light/dark cycle at the Division of Animal Resources, Emory University. All animals had free access to food and water. All animal protocols were reviewed and approved by the institutional animal care and use committee.
Trachea grafting
Tracheas were transplanted as previously described.6, 13, 14 Briefly, the mice were
MSC attenuate airway obstruction in allograft transplant recipients
Donor tracheal segments from BALB/c and C57BL/6 were heterotopically transplanted into C57BL/6 recipients. Group assignment was defined by the donating species. Allograft controls were made up of BALB/c tracheas transplanted into C57BL/6 recipients. Isograft controls were made up of C57BL/6 tracheas transplanted into C57BL/6 recipients. Tracheas were harvested on Day 10 and homogenized for Western blot analysis or fixed in formalin and then paraffin and sectioned for staining with H&E, Masson's
Discussion
In this study we investigated a potential therapeutic intervention to prevent the development of airway obstruction in a murine heterotopic model of lung transplantation and to further characterize its mechanisms. Based on previous studies, we hypothesized that MSC would modulate the pro-fibrotic response of allogeneic transplant. We presumed this would be mediated through modulatory effects on TGF-β.
To demonstrate the impact of MSC on the development of AO we used the heterotopic tracheal
Disclosure statement
This research was supported by the National Heart Lung and Blood Institute (5K01HL084683-02), the American Federation for Aging Research, Emory University (URC 2003100) and the McKelvey Center for Lung Transplantation at Emory University. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S.
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Cited by (34)
Bone Marrow-derived Mesenchymal Stem Cells and Chronic Allograft Disease in a Bronchiolitis Obliterans Animal Model
2020, Archivos de BronconeumologiaCitation Excerpt :Another example of this is the finding of BMSC (CrY+) taking part of the walls of neovessels, which are morphologically identical to endothelial cells (Fig. 5). Previous heterotopic tracheal transplant models have shown the capacity of stem cells to attenuate histopathological changes of BO after either topical or systemic administration.34–36 In this study, we have found that BMSC are able to nest and survive, detect an injury scenario, modify the histopathological course of BO lesions, and repair the structure.
The efficacy of mesenchymal stem cells in bronchiolitis obliterans syndrome after allogeneic HSCT: A multicenter prospective cohort study
2019, EBioMedicineCitation Excerpt :Our group also observed in a small pilot study that MSCs improved steroid-resistant chronic GVHD (cGVHD) with lung manifestations [15]. Preclinical studies have provided rationales for use of MSCs in BOS [16-18]. Accordingly, in this prospective cohort study, we assessed the efficacy and safety of MSCs combined with azithromycin and prednisone on lung function of patients with HSCT-related BOS.
Cardiopulmonary and histological characterization of an acute rat lung injury model demonstrating safety of mesenchymal stromal cell infusion
2016, CytotherapyCitation Excerpt :These results underscore the importance of evaluating the safety of MSC injections in animal models of lung injury before the initiation of human clinical studies, especially for pulmonary disorders. It has been shown that MSCs can protect the lungs from acute lung injury induced by bleomycin and reduce lung transplant rejection in rodent models [11–16]. However, detailed and clinically relevant pulmonary function tests (PFTs) have not been assessed in detail in any animal model [17].
Hepatocyte growth factor enhances the inflammation-alleviating effect of umbilical cord-derived mesenchymal stromal cells in a bronchiolitis obliterans model
2016, CytotherapyCitation Excerpt :Also, IL-10 may play a potential role in the development of experimental BO. In a murine model of allotropic tracheal transplantation, MSCs could induce an increase in IL-10 levels [20]. Our study showed that MSC treatment could increase the expression level of IL-10 that was down-regulated by heterograft not only in the transplanted trachea but also in the peripheral blood.
Treatment with placenta-derived mesenchymal stem cells mitigates development of bronchiolitis obliterans in a murine model
2014, Journal of Thoracic and Cardiovascular SurgeryMesenchymal stromal cells augment CD4+ and CD8+ T-cell proliferation through a CCL2 pathway
2013, CytotherapyCitation Excerpt :For example, MSC express B7 homolog 1 (B7-H1), which interacts with CD28, blocking an essential T-cell co-stimulatory pathway for the initiation of antigen-specific humoral and cell-mediated immune responses (13). We determined that in vivo delivery of intra-tracheal BMC had variable effects on allograft rejection, although the reduction in rejection was broadly similar to a recently reported study (26). Although not common, others have reported that MSC are not always immunosuppressive (27,28).