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Potentiating the Therapeutic Activity of Mesenchymal Stem Cells for Asthma Treatment

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Review of “Serum from Asthmatic Mice Potentiates the Therapeutic Effects of Mesenchymal Stromal Cells in Experimental Allergic Asthma” from STEM CELLS Translational Medicine by Stuart P. Atkinson 

As asthma patients suffer from chronic allergic immune and inflammatory responses in the airways, researchers have turned to the immunomodulatory power of mesenchymal stem cell (MSC) therapy as a potential treatment option. However, the inability of MSCs derived from the bone marrow to secrete the required levels of critical factors needed for tissue repair and remodeling [1-3] (See an SCTM article here!) suggests the necessity for an additional pre-treatment or “potentiation” step before MSC administration. 

Researchers from the laboratory of Patricia R. M. Rocco (Federal University of Rio de Janeiro, Rio de Janeiro, Brazil) recently assessed the potential of bronchoalveolar lavage fluid or serum derived from asthmatic mice to potentiate the therapeutic output of bone marrow MSCs and thereby improve asthma treatment. In their new STEM CELLS Translational Medicine article, Abreu et al. now report that pretreatment of MSCs with serum from asthmatic mice leads to a reduction in lung inflammation and remodeling and improvements to lung function, thereby providing a platform for future clinical trials in patients with asthma [4].

The mouse model of asthma employed by the authors involved the exposure of mice to house dust mite extract, a human-relevant model [5], followed 24 hours later by intratracheal administration of control and potentiated MSCs to mimic the clinical situation. Interestingly, MSCs potentiated with asthmatic serum triggered the highest reduction in inflammation and remodeling in the asthmatic lung and prompted an overall improvement in lung function when compared to control MSCs or bronchoalveolar lavage fluid-potentiated MSCs. Specifically, the authors noted a decrease in IL‐4, IL‐13, and eotaxin levels in bronchoalveolar lavage fluid, reduced immune cell counts in the bronchoalveolar lavage fluid, bone marrow, and mediastinal lymph nodes, and lower collagen fiber content in the lungs.

Further in vitro assessments delineated how serum-mediated potentiation improved the therapeutic potential of MSCs; overall, asthmatic serum-potentiated MSCs displayed higher levels of apoptosis, elevated expression of anti‐inflammatory and pro-resolution mediators (such as TGF‐β1, IFN‐γ, IL‐10, TSG‐6, IDO‐1, and IL‐1RN), and the polarization of macrophages to an anti‐inflammatory M2 phenotype.

While the authors believe their findings will provide a platform for future clinical trials in patients with asthma, they also note certain limitations to their study. Future studies hope to remedy this by including a broader range of potential allergens and ascertaining whether these may produce a different outcome, and by assessing a wider range of mediators to fully discover the mechanisms of MSC stimulation before administration.

For more on this MSC potentiation and stem cell treatment for asthma, stay tuned to the Stem Cells Portal!

References

  1. Abreu SC, Antunes MA, Xisto DG, et al., Bone Marrow, Adipose, and Lung Tissue-Derived Murine Mesenchymal Stromal Cells Release Different Mediators and Differentially Affect Airway and Lung Parenchyma in Experimental Asthma. STEM CELLS Translational Medicine 2017;6:1557-1567.
  2. Mariñas-Pardo L, Mirones I, Amor-Carro Ó, et al., Mesenchymal stem cells regulate airway contractile tissue remodeling in murine experimental asthma. Allergy 2014;69:730-740.
  3. Kitoko JZ, de Castro LL, Nascimento AP, et al., Therapeutic administration of bone marrow-derived mesenchymal stromal cells reduces airway inflammation without up-regulating Tregs in experimental asthma. Clinical & Experimental Allergy 2018;48:205-216.
  4. Abreu SC, Xisto DG, de Oliveira TB, et al., Serum from Asthmatic Mice Potentiates the Therapeutic Effects of Mesenchymal Stromal Cells in Experimental Allergic Asthma. STEM CELLS Translational Medicine 2019;8:301-312.
  5. Gregory LG and Lloyd CM, Orchestrating house dust mite-associated allergy in the lung. Trends in Immunology 2011;32:402-411.