Intraluminal Injection of Mesenchymal Stromal Cells in Spheroids Attenuates Experimental Colitis.

Autor: Molendijk I; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands., Barnhoorn MC; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands., de Jonge-Muller ES; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands., Mieremet-Ooms MA; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands., van der Reijden JJ; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands., van der Helm D; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands., Hommes DW; 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., van der Meulen-de Jong AE; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands., Verspaget HW; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands h.w.verspaget@lumc.nl.
Jazyk: angličtina
Zdroj: Journal of Crohn's & colitis [J Crohns Colitis] 2016 Aug; Vol. 10 (8), pp. 953-64. Date of Electronic Publication: 2016 Feb 19.
DOI: 10.1093/ecco-jcc/jjw047
Abstrakt: Background and Aims: 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.
Conclusion: 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.
(Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze: MEDLINE
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