Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2019; 25(33): 4892-4903
Published online Sep 7, 2019. doi: 10.3748/wjg.v25.i33.4892
Ex vivo effect of vascular wall stromal cells secretome on enteric ganglia
Giovanni Dothel, Chiara Bernardini, Augusta Zannoni, Maria Rosaria Spirito, Roberta Salaroli, Maria Laura Bacci, Monica Forni, Fabrizio De Ponti
Giovanni Dothel, Maria Rosaria Spirito, Fabrizio De Ponti, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40126, Italy
Chiara Bernardini, Augusta Zannoni, Roberta Salaroli, Maria Laura Bacci, Monica Forni, Department of Veterinary Medical Sciences, University of Bologna, Bologna 40064, Italy
Author contributions: Dothel G, Zannoni A, Bernardini C and Forni M conceived and designed the study; Dothel G, Salaroli R and Spirito MR performed the experiments; Dothel G, Bernardini C and Forni M wrote the paper; Dothel G performed the data analysis; Bacci ML carried out the procedures on pigs; De Ponti F and Forni M coordinated the research; all authors reviewed and participated to the paper drafting.
Supported by Fondazione del Monte di Bologna e Ravenna (ID ROL: FdM/3208).
Institutional review board statement: This study was approved by the institutional review board of National Institute of Health.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Bologna (approved experimental protocol for the use of guinea pigs: protocol number - 18/79/14; approved experimental protocol for the use of pigs: protocol number - 43-IX/9 all.37; 15/04/2013).
Conflict-of-interest statement: None of the authors have any potential conflicts of interest associated with this research.
ARRIVE guidelines statement: The present study was conceived, designed and performed following the ARRIVE guidelines. All the authors have read the ARRIVE guidelines and reviewed the manuscript accordingly.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Monica Forni, PhD, Associate Professor, Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra 50, Ozzano dell'Emilia, Bologna 40064, Italy.
Telephone: +39-51-2097913 Fax: +39-51-2097899
Received: April 11, 2019
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.

Keywords: Enteric nervous system, Mesenchymal stromal cells, Inflammatory bowel disease, Ganglia, Translational models

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.