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Deciphering the Influence of B Cells in MSC Therapy for Fibrosis

Review of “Amniotic MSCs reduce pulmonary fibrosis by hampering lung B‐cell recruitment, retention, and maturation” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Researchers from the laboratory of Anna Cargnoni (Fondazione Poliambulanza‐Istituto Ospedaliero, Brescia, Italy) have previously employed a rodent model of lung damage to demonstrate the potential of mesenchymal stem cells (MSCs) derived from the amniotic membrane of the human term placenta to inhibit fibrosis [1-3]. Secreted factors from MSCs are thought to dampen inflammatory processes associated with lung injury to inhibit the development and progression of fibrosis [4, 5].

Now, in a new STEM CELLS Translational Medicine article, the Cargnoni team report on their recent research that sought to investigate the crosstalk between human amniotic membrane MSCs and those immune cell populations involved in lung injury and fibrosis and correlate these findings with therapeutic outcome [6]. Fascinatingly, the authors now establish that the modulation of B cell responses by MSC therapy can blunt inflammatory responses in the lung and reduce progression to fibrosis.

Following the induction of bleomycin‐induced lung fibrosis in mice, the authors administered MSCs and then evaluated immune cells collected through bronchoalveolar lavage and lung tissues. As expected, MSC therapy inhibited the progression of lung injury to fibrosis, and the authors linked this effect to an increase in T regulatory cells, the polarization of macrophages toward the anti‐inflammatory M2 phenotype, and a reduction in antigen‐presentation by macrophages and dendritic cells. Furthermore, and for the first time, the authors also observed a significant reduction in pulmonary B‐cell recruitment, retention, and maturation following MSC therapy, as well as the inhibited formation and expansion of intrapulmonary lymphoid aggregates. Overall, this suggested that MSCs suppress inflammation by B cells that function as antigen-presenting cells for T lymphocytes in the injured lungs to inhibit the development of fibrosis. Of additional note, the therapeutic capacity of freshly isolated MSCs and short-term in vitro expanded MSCs remained similar, which should encourage the translation of this therapeutic strategy into the clinic.

While this fascinating new study provides evidence for the therapeutic and translational potential of human amniotic membrane MSCs as a means to inhibit inflammation‐related fibrotic disease, the authors highlight the utility of monitoring MSCs during the long-term in vitro expansion of MSCs required to generate therapeutically relevant cell numbers to evaluate any influence in their curative capacity.

For more on the potential of human amniotic membrane MSC therapy in the treatment of inflammation‐related fibrotic diseases, stay tuned to the Stem Cells Portal!

References

  1. Cargnoni A, Gibelli L, Tosini A, et al., Transplantation of Allogeneic and Xenogeneic Placenta-Derived Cells Reduces Bleomycin-Induced Lung Fibrosis. Cell Transplantation 2009;18:405-422.
  2. Cargnoni A, Ressel L, Rossi D, et al., Conditioned medium from amniotic mesenchymal tissue cells reduces progression of bleomycin-induced lung fibrosis. Cytotherapy 2012;14:153-161.
  3. Cargnoni A, Piccinelli EC, Ressel L, et al., Conditioned medium from amniotic membrane-derived cells prevents lung fibrosis and preserves blood gas exchanges in bleomycin-injured mice - specificity of the effects and insights into possible mechanisms. Cytotherapy 2014;16:17-32.
  4. Kolahian S, Fernandez IE, Eickelberg O, et al., Immune Mechanisms in Pulmonary Fibrosis. American Journal of Respiratory Cell and Molecular Biology 2016;55:309-322.
  5. Hoyne GF, Elliott H, Mutsaers SE, et al., Idiopathic pulmonary fibrosis and a role for autoimmunity. Immunology & Cell Biology 2017;95:577-583.
  6. Cargnoni A, Romele P, Bonassi Signoroni P, et al., Amniotic MSCs reduce pulmonary fibrosis by hampering lung B-cell recruitment, retention, and maturation. STEM CELLS Translational Medicine 2020;9:1023-1035.