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Mesenchymal stem cell-derived factors protect the intestines from experimental colitis in organ culture.
Introduction: Although the mesenchymal stromal cells (MSC) have shown therapeutic potential in intestinal tissue repair, controversy remains concerning to the short survival and their poor biodistribution in recipient tissues suggesting that the therapeutic effects afforded by MSC transplantation are related to the paracrine interactions between MSC and resident cells. Therefore, this paracrine mechanism may have therapeutic potential for cell-free treatment strategies using MSC-secreted bioactive factors.
Objetivos - Metodologia - Resultados - Discussão dos Resultados/Objectives - Methodology - Results - Discussion of Results/Objetivos - Metodología - Resultados - Discusión de los resultados
Objectives: To investigate the paracrine role of MSC in three-dimensional culture of mouse colon with DSS-induced colitis.
Methods: Acute colitis was induced in mice by oral administration of 2% dextran sulfate sodium (DSS) for 7 days. Inflammatory responses were assessed on the basis of clinical signs, morphological, and histopathological parameters. On days 2 and 5, colonic explants were removed and a three-dimensional culture model was performed for cell biological investigations in an in vivo-like environment. The structural integrity of the intestinal mucosa was tested by treating the cultures with MSC or conditioned medium (CM) for 24 h. The tissue was then prepared for histology/immunohistochemistry, and the culture supernatants were assayed for Il-6 production.
Results and Discussion: Histological analysis demonstrated MSC and CM treatment reduced colon damage in organ culture. An increased in cell proliferation (Ki-67 staining) was observed after CM treatment in colonic explants. Additionally, the MSC treatment was able to reduce CD3+ cells. The therapeutic effect of MSC and CM was most likely mediated by the downregulation of pro-inflammatory cytokine IL-6. Accordingly, the intestinal in vitro model has demonstrated to be potentially useful for studying cellular interactions in a three-dimensional cell arrangement. Moreover, both MSC and CM treatments provide strong evidence that they can alleviated the colonic damage in organ culture.
Considerações Finais/Final considerations/Consideraciones finales
Conclusion: These results suggest MSC-secreted factors are capable of providing support without cell transplantation to protect from colon inflammation caused by DSS-induced colitis.
Palavras-chave/Key words/Palabras clave
Organ culture, three-dimensional culture, DSS-induced colitis, conditioned medium, mesenchymal stromal cell, cell therapy.
Mesenchymal stem cells/adultas
FABIANY DA COSTA GONÇALVES, Michele Aramburu Serafini, Ana Carolina Henzel Raymundo, Bianca Pfaffenseller, Anelise Bergmann Araújo, Fernanda Visioli, Ana Helena Paz