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Placental and Amniotic Fluid Stem Cells: A New Means to Prevent Inflammatory Disease?

Review of “Stromal Cells from Perinatal and Adult Sources Modulate the Inflammatory Immune Response in Vitro by Decreasing Th1 Cell Proliferation and Cytokine Secretion” from STEM CELLS Translational Medicine by Stuart P. Atkinson

While many types of autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, corneal transplant rejection, and type I diabetes, involve T helper 1 (Th1) cell‐mediated inflammation, current single or combination therapies, such as Th1 pro-inflammatory cytokine antagonists, exhibit limited efficacy in chronic and severe forms of disease. In the search for a better therapeutic approach, researchers led by Sean V. Murphy (Wake Forest School of Medicine, Winston-Salem, NC, United States) have investigated a potential role for mesenchymal-like stem cells derived from perinatal tissues such as the placenta and amniotic fluid in the modulation of the inflammatory response of immune cells. 

Said cells have received much recent attention due to their ease of collection, ready availability, high abundance, and high proliferation rates [1, 2], as well as their ability to modulate the immune system towards an anti-inflammatory, pro-resolution state [3, 4]. In their new STEM CELLS Translational Medicine article, Khoury et al. compared the potential immunomodulatory properties of amniotic fluid‐derived stem cells (AFSCs), placenta‐derived stem cells (PLSCs), and bone marrow‐derived mesenchymal stem cells (BM‐MSCs) on antigen‐stimulated leukocytes, lymphocytes, neutrophils, and T cell subsets derived from healthy donor blood [5].

Overall, coculture of AFSCs, PLSC, and BM-MSCs led to a potent decrease in the expression of genes coding inflammatory cytokines and enzymes (including interleukin 1β, interferon-γ (IFN‐γ), and tissue necrosis factor‐α), as well as neutrophil elastase, and the transcription factor NF‐B in leukocytes stimulated with lipopolysaccharide, a Gram‐negative bacteria component that triggers an inflammatory immune response. While PLSCs displayed the highest activity of the stem cells evaluated, the immunomodulatory effect did not require cell-to-cell contact, suggesting a role of stem cell-secreted factors.

Further analysis of PLSCs, as they prompted the most widespread reduction of cytokine levels and significant suppression of lymphocyte proliferation, employed coculture with peripheral blood mononuclear cells stimulated with phytohemagglutinin, a plant lectin that mimics inflammation that increases pro-inflammatory cytokine levels. Encouragingly, PLSC coculture led to decreased lymphocyte proliferation and, importantly, a decrease in the numbers of Th1 lymphocytes and levels of secreted IFN‐γ.

In summary, stem cells of the placenta and amniotic fluid exhibit immunomodulatory capabilities similar to that of BM‐MSCs and, thus, may represent an easier to isolate stem cell type for use as a therapeutic approach to inflammatory disease. Furthermore, the robust effect of PLSCs on the suppression and function of Th1 subsets suggests further research towards their specific application in Th1‐related conditions.

For more on the immunomodulatory powers of stem cells derived from the placenta and amniotic fluid, stay tuned to the Stem Cells Portal!

References

  1. Ilancheran S, Moodley Y, and Manuelpillai U, Human Fetal Membranes: A Source of Stem Cells for Tissue Regeneration and Repair? Placenta 2009;30:2-10.
  2. Abomaray FM, Al Jumah MA, Alsaad KO, et al., Phenotypic and Functional Characterization of Mesenchymal Stem/Multipotent Stromal Cells from Decidua Basalis of Human Term Placenta. Stem Cells International 2016;2016:18.
  3. Pianta S, Magatti M, Vertua E, et al., Amniotic mesenchymal cells from pre-eclamptic placentae maintain immunomodulatory features as healthy controls. Journal of Cellular and Molecular Medicine 2016;20:157-169.
  4. Yang H, Sun J, Li Y, et al., Human umbilical cord-derived mesenchymal stem cells suppress proliferation of PHA-activated lymphocytes in vitro by inducing CD4+CD25highCD45RA+ regulatory T cell production and modulating cytokine secretion. Cellular Immunology 2016;302:26-31.
  5. Khoury O, Atala A, and Murphy SV, Stromal cells from perinatal and adult sources modulate the inflammatory immune response in vitro by decreasing Th1 cell proliferation and cytokine secretion. STEM CELLS Translational Medicine 2020;9:61-73.