title: Intraperitoneal but not intravenous cryopreserved mesenchymal stromal cells home to the inflamed colon and ameliorate experimental colitis.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSCs) were shown to have immunomodulatory activity and have been applied for treating immune-mediated disorders. We compared the homing and therapeutic action of cryopreserved subcutaneous adipose tissue (AT-MSCs) and bone marrow-derived mesenchymal stromal cells (BM-MSCs) in rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis.
  
  
  METHODS
  After colonoscopic detection of inflammation AT-MSCs or BM-MSCs were injected intraperitoneally. Colonoscopic and histologic scores were obtained. Density of collagen fibres and apoptotic rates were evaluated. Cytokine levels were measured in supernatants of colon explants. For cell migration studies MSCs and skin fibroblasts were labelled with Tc-99m or CM-DiI and injected intraperitonealy or intravenously.
  
  
  RESULTS
  Intraperitoneal injection of AT-MSCs or BM-MSCs reduced the endoscopic and histopathologic severity of colitis, the collagen deposition, and the epithelial apoptosis. Levels of TNF-α and interleukin-1β decreased, while VEGF and TGF-β did not change following cell-therapy. Scintigraphy showed that MSCs migrated towards the inflamed colon and the uptake increased from 0.5 to 24 h. Tc-99m-MSCs injected intravenously distributed into various organs, but not the colon. Cm-DiI-positive MSCs were detected throughout the colon wall 72 h after inoculation, predominantly in the submucosa and muscular layer of inflamed areas.
  
  
  CONCLUSIONS
  Intraperitoneally injected cryopreserved MSCs home to and engraft into the inflamed colon and ameliorate TNBS-colitis.
authors.affiliation: Laboratório de Imunologia Celular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Morgana T L
authors.initials: MT
authors.lastname: Castelo-Branco
authors.forename: Igor D P
authors.initials: ID
authors.lastname: Soares
authors.forename: Daiana V
authors.initials: DV
authors.lastname: Lopes
authors.forename: Fernanda
authors.initials: F
authors.lastname: Buongusto
authors.forename: Cesonia A
authors.initials: CA
authors.lastname: Martinusso
authors.forename: Alyson
authors.initials: A
authors.lastname: do Rosario
authors.forename: Sergio A L
authors.initials: SA
authors.lastname: Souza
authors.forename: Bianca
authors.initials: B
authors.lastname: Gutfilen
authors.forename: Lea Mirian B
authors.initials: LM
authors.lastname: Fonseca
authors.forename: Celeste
authors.initials: C
authors.lastname: Elia
authors.forename: Kalil
authors.initials: K
authors.lastname: Madi
authors.forename: Alberto
authors.initials: A
authors.lastname: Schanaider
authors.forename: Maria Isabel D
authors.initials: MI
authors.lastname: Rossi
authors.forename: Heitor S P
authors.initials: HS
authors.lastname: Souza
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology; D019070:Cell Lineage; D002465:Cell Movement; D003092:Colitis / Q000150:complications / Q000473:pathology / Q000628:therapy*; D003094:Collagen / Q000378:metabolism; D003106:Colon / Q000473:pathology*; D003113:Colonoscopy; D015925:Cryopreservation; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D007249:Inflammation / Q000150:complications / Q000473:pathology*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D050151:Subcutaneous Fat / Q000166:cytology; D014302:Trinitrobenzenesulfonic Acid; D014945:Wound Healing
chemical_list: D016207:Cytokines; D014302:Trinitrobenzenesulfonic Acid; D003094:Collagen