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
Mesenchymal stromal cell (MSC)-based therapy is currently under study to treat inflammatory bowel diseases. MSC bioactive products could represent a valid alternative to overcome issues associated with systemic whole-cell therapies. However, MSC anti-inflammatory mechanisms differ between rodents and humans, impairing the reliability of preclinical models.
To evaluate the effect of conditioned medium (CM) derived from porcine vascular wall MSCs (pVW-MSCs) on survival and differentiation of porcine and guinea pig enteric ganglia exposed to lipopolysaccharide (LPS).
Primary cultures of enteric ganglia were obtained by mechanic and enzymatic digestion of ileum resections from guinea pigs (Cavia porcellus) (GPEG) and pigs (Suus scrofa) (PEG). pVW-MSCs were derived by enzymatic digestion from vascular wall resections of porcine aorta and tested by immunoflowcytometry for MSC immune profile. Enteric ganglia were treated with increasing concentrations of LPS, CM derived by pVW-MSCs or a combination of CM and LPS 1 µg/mL. Cell count and morphometric analysis of HuD positive neurons and glial fibrillary acidic protein positive glial cells were performed by immunofluorecent staining of cultured ganglia.
PEG showed a higher number of neurons compared to GPEG. Overall, CM exerted a protective role on LPS-treated enteric ganglia. CM in combination with LPS increased the number of glial cells per ganglion in both cultures evoking glial cells differentiation in porcine cultures.
These findings suggest an immunomodulating activity of pVW-MSCs mediators on the enteric nervous system in inflammatory conditions.
Core tip: Secretome of porcine vascular wall mesenchymal stromal cells (pVW-MSCs) induced an increase of glial cell number in swine and guinea pig-derived enteric ganglia. Co-treatment of enteric ganglia with lipopolysaccharide and conditioned medium promoted glial cell differentiation only in pigs. These data indicate an immune activation promoted by pVW-MSCs which could be more specific in higher mammals, suggesting a careful consideration of the animal models used in research studies on cell-based therapies.