Ex vivo effect of vascular wall stromal cells secretome on enteric ganglia  

作　　者：Giovanni Dothel Chiara Bernardini Augusta Zannoni Maria Rosaria Spirito Roberta Salaroli Maria Laura Bacci Monica Forni Fabrizio De Ponti 

机构地区：[1]Department of Medical and Surgical Sciences,University of Bologna,Bologna 40126,Italy [2]Department of Veterinary Medical Sciences,University of Bologna,Bologna 40064,Italy

出　　处：《World Journal of Gastroenterology》2019年第33期4892-4903,共12页世界胃肠病学杂志（英文版）

基　　金：Supported by Fondazione del Monte di Bologna e Ravenna(ID ROL:Fd M/3208)

摘　　要：BACKGROUND 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.AIM 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).METHODS 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 1μg/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.RESULTS 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.CONCLUSION These findings suggest an immunomodulating activity of pVW-MSCs mediators on the enteric nervous system in inflammatory conditions.BACKGROUND 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.AIM To evaluate the effect of conditioned medium(CM) derived from porcine vascular wall MSCs(p VW-MSCs) on survival and differentiation of porcine and guinea pig enteric ganglia exposed to lipopolysaccharide(LPS).METHODS 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). p VW-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 p VW-MSCs or a combination of CM and LPS 1 μg/mL.Cell count and morphometric analysis of Hu D positive neurons and glial fibrillary acidic protein positive glial cells were performed by immunofluorecent staining of cultured ganglia.RESULTS 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.CONCLUSION These findings suggest an immunomodulating activity of p VW-MSCs mediators on the enteric nervous system in inflammatory conditions.

关 键 词：ENTERIC nervous system MESENCHYMAL STROMAL cells Inflammatory BOWEL disease GANGLIA Translational models 

分 类 号：R[医药卫生]