Naïve rat umbilical cord matrix stem cells significantly attenuate mammary tumor growth through modulation of endogenous immune responses

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dc.contributor.author Kawabata, Atsushi
dc.contributor.author Ohta, Naomi
dc.contributor.author Seiler, Garret
dc.contributor.author Pyle, Marla M.
dc.contributor.author Ishiguro, Susumu
dc.contributor.author Zhang, Yongqing
dc.contributor.author Becker, Kevin G.
dc.contributor.author Troyer, Deryl L.
dc.contributor.author Tamura, Masaaki
dc.date.accessioned 2013-05-06T21:06:28Z
dc.date.available 2013-05-06T21:06:28Z
dc.date.issued 2013-05-06
dc.identifier.uri http://hdl.handle.net/2097/15743
dc.description.abstract Background: Un-engineered human and rat umbilical cord matrix stem cells (rUCMSC) attenuate growth of several types of tumors in mice and rats. However, the mechanism by which UCMSC attenuate tumor growth has not been studied rigorously. Methods- The possible mechanisms of tumor growth attenuation by rUCMSC were studied using orthotopic Mat B III rat mammary tumor grafts in female F344 rats. Tumor-infiltrating leukocytes were identified and quantified by immunohistochemical image analysis. Potential cytokines involved in lymphocyte infiltration in the tumors were determined by microarray and Western blot analysis. The Boyden chamber migration assay was performed for the functional analysis of identified cytokines. Results: rUCMSC markedly attenuated the tumor growth; this attenuation was accompanied by considerable lymphocyte infiltration. Immunohistochemical analysis revealed that the majority of infiltrating lymphocytes in the rUCMSC-treated tumors were CD3+ T cells. In addition, treatment with rUCMSC significantly increased infiltration of CD 8+ and CD4+ T cells and NK cells throughout tumor tissue. CD68+ monocytes/macrophages and FoxP3+ regulatory T cells were scarcely observed, only in the tumors of the PBS control group. Microarray analysis of rUCMSC identified that monocyte chemotactic protein (MCP)-1 is involved in rUCMSCinduced lymphocyte infiltration in the tumor tissues. Discussion: These results suggest that naïve rUCMSC attenuated mammary tumor growth at least in part by enhancing host anti-tumor immune responses. Thus, naïve UCMSC can be used as powerful therapeutic cells for breast cancer treatment, and MCP-1 may be a key molecule to enhance the effect of UCMSC at the tumor site. en_US
dc.language.iso en_US en_US
dc.relation.uri http://www.sciencedirect.com/science/article/pii/S1465324913001199 en_US
dc.subject Rat umbilical cord matrix stem cells en_US
dc.subject Mammary tumor en_US
dc.subject Immune response en_US
dc.subject T cells en_US
dc.subject Macrophages en_US
dc.title Naïve rat umbilical cord matrix stem cells significantly attenuate mammary tumor growth through modulation of endogenous immune responses en_US
dc.type Article (author version) en_US
dc.date.published 2013 en_US
dc.citation.doi doi:10.1016/j.jcyt.2013.01.006 en_US
dc.citation.epage 597 en_US
dc.citation.issue 5 en_US
dc.citation.jtitle Cytotherapy en_US
dc.citation.spage 586 en_US
dc.citation.volume 15 en_US
dc.contributor.authoreid isusumu en_US
dc.contributor.authoreid troyer en_US
dc.contributor.authoreid masaakit en_US
dc.contributor.authoreid mpyle en_US


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