15 June 2020
Mesenchymal stem cells (MSCs), or the cells that differentiate into bone, cartilage, muscle or fat cells, have a versatile use in developing new therapies. They can trigger activities in other cells or change how cell populations respond to certain stimuli, and this versatility creates a multitude of possibilities for scientists when it comes to tackling complex diseases like cancer.
Dunia Jawdat and colleagues at KAIMRC’s Stem Cell and Regenerative Medicine Department, and co-workers across Saudi Arabia have now demonstrated that MSCs taken from the foetal part of the human placenta can influence how natural killer (NK) immune cells express anti-inflammatory and anti-tumour molecules. Their results could inform future cancer therapies.
NK cells are a key component of the innate immune system, and can either prevent pathogenic cell growth and replication, or destroy cells by bursting or dissolving them. Receptor proteins on the surface of NK cells mediate these activities by binding to target cells and either activating or inhibiting a destructive response.
Previous studies, including research conducted by the KAIMRC team, have demonstrated that pMSCs can suppress immune responses and may be able to control immune cell functioning. However, precisely how pMSCs interact with different immune cell populations is unclear.
In their study, published in Stem Cell Research and Therapy journal, Jawdat’s team used both non-activated ‘fresh’ NK cells, and NK cells which had been activated by cytokine signalling prior to use. They cultured each NK cell population at different ratios with pMSCs to determine whether NK cells would interact with or destroy the stem cells.
While the activated NK cells actively destroyed the pMSCs, the fresh NK cells did not. The team identified an NK cell receptor that could be responsible for the attack on pMSCs, and could potentially be inactivated to prevent damage to pMSCs. Notably, preconditioning NK cells with pMSCs did not reduce the NK cells’ ability to destroy breast cancer cell lines.
Further examination showed that co-cultured NK cells significantly increased their production of anti-tumour molecules, including the secretion of IL1ra, a natural anti-inflammatory cytokine.
“Our data suggest that pMSCs could be used to treat cancers by enhancing the anti-cancer activity of NK cells in vitro,” the researchers reported in their paper. “Before realizing this possibility, further studies are needed to elucidate the molecular mechanisms that underlie the enhancement of the anti-tumor activities of NK cells by pMSCs.”
Abumaree, M.H. et al. Preconditioning human natural killer cells
with chorionic villous mesenchymal stem cells stimulates their expression of
inflammatory and anti-tumor molecules. Stem Cell Research and Therapy 10 (2019). | article