Published online Sep 7, 2019. doi: 10.3748/wjg.v25.i33.4892
Peer-review started: April 11, 2019
First decision: May 17, 2019
Revised: May 31, 2019
Accepted: June 8, 2019
Article in press: June 8, 2019
Published online: September 7, 2019
There is growing interest on mesenchymal stromal cells (MSC) as a novel therapeutic strategy to treat auto-immune and inflammatory diseases. However, identifying optimal MSC sources and limited reliability of current experimental models still represent a challenge in this field. Pigs represent more closely human physiology and an accessible resource for ex vivo procedures. Recently, our group isolated a population of pericytes from porcine aortic wall with an MSC profile, currently cited as porcine vascular wall-MSC (pVW-MSC).
Inflammatory bowel diseases (IBDs), comprising the two major forms ulcerative colitis and Crohn’s disease, are characterized by an aberrant immune response leading to severe damage of the intestinal wall and functioning. Current trials are evaluating the application of cell-based therapies for the treatment of IBDs. The present study describes the effect of pVW-MSC-conditioned medium (CM) on enteric ganglia in two ex vivo models of IBDs in order to investigate a potential development of MSC-based treatment of IBDs.
To evaluate the effect of pVW-MSC secretome on survival and differentiation of enteric ganglionic cells isolated by guinea pigs (GPEG) and pigs (PEG) and exposed to lipopolysaccharide (LPS).
The expression of standard MSC markers in pVW-MSC were assessed by flow cytometry. Increasing concentration of LPS were tested in both GPEG and PEG cultures. CM derived by pVW-MSC cultures were added alone or in combination with 1µg of LPS in GPEG and PEG cultures. Ganglionic cells were double-stained with antibodies directed to the pan-neuronal marker, HuD and the glial fibrillary acidic protein, GFAP. Cell count and morphometric analysis were performed to determine changes of neuronal and glial population.
Guinea-pig neurons and glial cells decreased and increased respectively in response to high concentrations of LPS. These changes were not observed in pig primary cultures. pVW-MSC secretome increased the number and differentiation of glial cells compared to neurons with a more pronounced effect in PEG and in combination with LPS.
These data showed a higher resilience of pig enteric ganglia to the main bacterial product LPS compared to guinea pig and a higher responsiveness of glial cells to pVW-MSC secreted mediators.
Neuro-immune changes induced by pVW-MSC represent an essential aspect in the development of cell-based therapies. Further studies are warranted to investigate inter-species differences of pVW-MSC secretome.