title: Intraluminal Injection of Mesenchymal Stromal Cells in Spheroids Attenuates Experimental Colitis.
abstract: OBJECTIVE
  In recent years, mesenchymal stromal cells [MSCs] emerged as a promising therapeutic option for various diseases, due to their immunomodulatory properties. We previously observed that intraperitoneally injected MSCs in experimental colitis form spherical shaped aggregates. Therefore, we aggregated MSCs in vitro into spheroids and injected them intraluminally in mice with established colitis, to investigate whether these MSC spheroids could alleviate the colitis.
  
  
  METHODS
  We injected 0.5 x 10(6) MSCs in spheroids, 2.0 x 10(6) MSCs in spheroids, or phosphate-buffered saline [PBS] as a treatment control, via an enema in mice with established dextran sulphate sodium [DSS]-induced colitis. Body weight was measured daily and disease activity score was determined at sacrifice. Endoscopy was performed to evaluate mucosal healing. After sacrifice, both systemic and local inflammatory responses were evaluated.
  
  
  RESULTS
  Intraluminally injected MSC spheroids alleviated DSS-induced colitis, resulting in significantly less body weight loss and lower disease activity score at sacrifice when a high dose of MSC spheroids was administered. However, the percentage of mucosal lesions in the distal colon and endoscopy scores were not significantly lower after treatment with 2.0 x 10(6) MSCs in spheroids compared with PBS-treated mice. Systemic inflammation marker serum amyloid A [SAA] was significantly reduced after treatment with 2.0 x 10(6) MSCs in spheroids. In addition, local cytokine levels of IFN-ɣ, TNF-α, IL-6, and IL-17a, as well as numbers of macrophages and neutrophils, showed a clear decrease-though not always significant-after intraluminal injection of the MSC spheroids.
  
  
  CONCLUSIONS
  Intraluminally injected MSC spheroids at least partially attenuate experimental colitis, with fewer phagocytes and proinflammmatory cytokines, when a high dose of MSCs in spheroids was administered.
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ilse
authors.initials: I
authors.lastname: Molendijk
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marieke C
authors.initials: MC
authors.lastname: Barnhoorn
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Eveline S M
authors.initials: ES
authors.lastname: de Jonge-Muller
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marij A C
authors.initials: MA
authors.lastname: Mieremet-Ooms
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Johan J
authors.initials: JJ
authors.lastname: van der Reijden
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Danny
authors.initials: D
authors.lastname: van der Helm
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands Division of Digestive Diseases, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Hommes
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: van der Meulen-de Jong
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands h.w.verspaget@lumc.nl.
authors.forename: Hein W
authors.initials: HW
authors.lastname: Verspaget
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016264:Dextran Sulfate; D005260:Female; D007267:Injections; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D018874:Spheroids, Cellular / Q000637:transplantation*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016264:Dextran Sulfate
keywords: Experimental colitis; mesenchymal stromal cell; spheroid