Human Mesenchymal Stem Cells Reduce Lung Injury in Immunocompromised Mice but Not in Immunocompetent Mice

Lim, Rebecca; Milton, Phillipa Louise; Murphy, Sean V.; Dickinson, Hayley; Chan, Sze Wah Samuel; Jenkin, Graham

doi:10.1159/000343078

Cited by 24 publications

(17 citation statements)

References 37 publications

(43 reference statements)

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“…A growing number of studies demonstrates efficacy of human MSCs in lung injury models in both immune-deficient and immune-competent mice [31][32][33][34][35]. However, a recent comparison demonstrated that human MSCs were more effective in ameliorating bleomycin-induced lung injury in immune-deficient mice than in immune-competent mice [46]. The current study demonstrates that hMSCs are potent in ameliorating mixed Th2/Th17 AHR, lung inflammation, and antigen-specific Th2/Th17 phenotype.…”

Section: Discussionmentioning

confidence: 99%

Freshly Thawed and Continuously Cultured Human Bone Marrow-Derived Mesenchymal Stromal Cells Comparably Ameliorate Allergic Airways Inflammation in Immunocompetent Mice

Cruz

Borg

Goodwin

et al. 2015

Stem Cells Translational Medicine

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Recent data suggest that freshly thawed previously frozen mesenchymal stromal cells (MSCs) may not have the same effectiveness or breadth of anti-inflammatory activities as do continuously cultured MSCs. This has significant implications for clinical use, in which many infusion schemes use frozen cells thawed at the bedside for administration. The available data, however, predominantly evaluate in vitro MSC properties, and so far there has been limited in vivo analysis. To further assess this issue, we compared freshly thawed (thawed) versus continuously cultured (fresh) human bone marrowderived MSC (hMSC) administration in a mouse model of mixed Th2/Th17 allergic airway inflammation induced by Aspergillus hyphal extract (AHE) exposures in immunocompetent C57Bl/6 mice. Control cell populations included fresh versus thawed murine bone marrow-derived MSCs (mMSCs) and human lung fibroblasts (HLFs). Systemic administration of both thawed and fresh hMSCs and mMSCs, but not HLFs, at the onset of antigen challenge in previously sensitized mice significantly ameliorated the AHE-provoked increases in airway hyper-reactivity, lung inflammation, and antigenspecific CD4 T-cell Th2 and Th17 phenotype. Notably, there was no difference in effects of fresh versus thawed hMSCs or mMSCs on any outcome measured except for some variability in the effects on the bronchoalveolar lavage fluid composition. These results demonstrated potent xenogeneic effects of human MSCs in an immunocompetent mouse model of allergic airways inflammation and that thawed MSCs are as effective as fresh MSCs. The question of fresh versus thawed MSC effectiveness needs to be investigated carefully and may differ in different in vivo disease-specific models. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:615-624 SIGNIFICANCEThis study addressed whether freshly thawed mesenchymal stromal cells (MSCs) are as effective in in vivo settings as those that have been continuously cultured. It also provided further data demonstrating that xenogeneic use of MSCs in immunocompetent mice is as effective as murine MSCs. This information provides further support and direction for potential clinical use of MSCs in patients with severe asthma.

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Section: Discussionmentioning

confidence: 99%

Freshly Thawed and Continuously Cultured Human Bone Marrow-Derived Mesenchymal Stromal Cells Comparably Ameliorate Allergic Airways Inflammation in Immunocompetent Mice

Cruz

Borg

Goodwin

et al. 2015

Stem Cells Translational Medicine

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“…This issue is also being investigated in the context of lung diseases. In a model of bleomycin-induced lung injury, it has been recently found that hMSC xenotransplantation into immunocompromised SCID mice resulted in reparative effects on respiratory physiology as well as on lung inflammation and fibrosis, while not having such effects in immunocompetent mice [Lim et al, 2013]. These results indicate that priming of MSCs in different immunological milieu may also make the difference in terms of beneficial effects in the lung disease context.…”

Section: Immunomodulatory Effects Of Mscsmentioning

confidence: 99%

Paracrine Effects and Heterogeneity of Marrow-Derived Stem/Progenitor Cells: Relevance for the Treatment of Respiratory Diseases

Conese

Carbone

Castellani

et al. 2013

Cells Tissues Organs

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Stem cell-based treatment may represent a hope for the treatment of acute lung injury and pulmonary fibrosis, and other chronic lung diseases, such as cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD). It is well established in preclinical models that bone marrow-derived stem and progenitor cells exert beneficial effects on inflammation, immune responses and repairing of damage in virtually all lung-borne diseases. While it was initially thought that the positive outcome was due to a direct engraftment of these cells into the lung as endothelial and epithelial cells, paracrine factors are now considered the main mechanism through which stem and progenitor cells exert their therapeutic effect. This knowledge has led to the clinical use of marrow cells in pulmonary hypertension with endothelial progenitor cells (EPCs) and in COPD with mesenchymal stromal (stem) cells (MSCs). Bone marrow-derived stem cells, including hematopoietic stem/progenitor cells, MSCs, EPCs and fibrocytes, encompass a wide array of cell subsets with different capacities of engraftment and injured tissue-regenerating potential. The characterization/isolation of the stem cell subpopulations represents a major challenge to improve the efficacy of transplantation protocols used in regenerative medicine and applied to lung disorders.

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“…Differences between syngeneic, allogeneic, and xenogeneic MSC administration have been less well explored in preclinical lung injury models. A growing number of studies demonstrate the efficacy of human MSCs in lung injury models in immune-deficient (4,281,285) and immune-competent mice (4,260,261,273,274,285,294). However, a recent head-tohead comparison of human MSCs in ameliorating bleomycin-induced lung injury in immune-deficient versus immune-competent mice suggests that human MSCs may be less effective in immune-competent mice (285).…”

Section: Vermont Stem Cell Conferencementioning

confidence: 99%

“…A growing number of studies demonstrate the efficacy of human MSCs in lung injury models in immune-deficient (4,281,285) and immune-competent mice (4,260,261,273,274,285,294). However, a recent head-tohead comparison of human MSCs in ameliorating bleomycin-induced lung injury in immune-deficient versus immune-competent mice suggests that human MSCs may be less effective in immune-competent mice (285). Although the overall consistency of studies demonstrating the ability of MSCs to ameliorate different types of lung injuries is encouraging, continued rigor must be applied to understand the mechanisms of MSC effects when comparing MSCs isolated by different protocols and obtained from different sources.…”

Section: Vermont Stem Cell Conferencementioning

confidence: 99%

Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases. Comprehensive Review of the Recent Literature 2010–2012

Weiss

2013

Annals ATS

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A conference, "Stem Cells and Cell Therapies in Lung Biology and Lung Diseases," was held July 25 to 28, 2011, at the University of Vermont to review the current understanding of the role of stem and progenitor cells in lung repair after injury and to review the current status of cell therapy and ex vivo bioengineering approaches for lung diseases. These are rapidly expanding areas of study that provide further insight into and challenge traditional views of mechanisms of lung repair after injury and pathogenesis of several lung diseases. The goals of the conference were to summarize the current state of the field, to discuss and debate current controversies, and to identify future research directions and opportunities for basic and translational research in cell-based therapies for lung diseases. The goal of this article, which accompanies the formal conference report, is to provide a comprehensive review of the published literature in lung regenerative medicine from the last conference report through December 2012.

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Human Mesenchymal Stem Cells Reduce Lung Injury in Immunocompromised Mice but Not in Immunocompetent Mice

Cited by 24 publications

References 37 publications

Freshly Thawed and Continuously Cultured Human Bone Marrow-Derived Mesenchymal Stromal Cells Comparably Ameliorate Allergic Airways Inflammation in Immunocompetent Mice

Freshly Thawed and Continuously Cultured Human Bone Marrow-Derived Mesenchymal Stromal Cells Comparably Ameliorate Allergic Airways Inflammation in Immunocompetent Mice

Paracrine Effects and Heterogeneity of Marrow-Derived Stem/Progenitor Cells: Relevance for the Treatment of Respiratory Diseases

Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases. Comprehensive Review of the Recent Literature 2010–2012

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