The therapeutic potential of human adipose-derived mesenchymal stem cells producing CXCL10 in a mouse melanoma lung metastasis model

Mirzaei, H. and Salehi, H. and Oskuee, R.K. and Mohammadpour, A. and Mirzaei, H.R. and Sharifi, M.R. and Salarinia, R. and Darani, H.Y. and Mokhtari, M. and Masoudifar, A. and Sahebkar, A. and Salehi, R. and Jaafari, M.R. (2018) The therapeutic potential of human adipose-derived mesenchymal stem cells producing CXCL10 in a mouse melanoma lung metastasis model. Cancer Letters, 419. pp. 30-39.

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Abstract

Abstract Interferon γ-induced protein 10 kDa (IP-10) is a potent chemoattractant and has been suggested to enhance antitumor activity and mediate tumor regression through multiple mechanisms of action. Multiple lines of evidence have indicated that genetically-modified adult stem cells represent a potential source for cell-based cancer therapy. In the current study, we assessed therapeutic potential of human adipose derived mesenchymal stem cells (hADSC) genetically-modified to express IP-10 for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma. A Piggybac vector encoding IP-10 was employed to transfect hADSC ex vivo. Expression and bioactivity of the transgenic protein from hADSCs expressing IP-10 were confirmed prior to in vivo studies. Our results indicated that hADSCs expressing IP-10 could inhibit the growth of B16F10 melanoma cells and significantly prolonged survival. Immunohistochemistry analysis, TUNEL assay and western blot analysis indicated that hADSCs expressing IP-10 inhibited tumor cell growth, hindered tumor infiltration of Tregs, restricted angiogenesis and significantly prolonged survival. In conclusion, our results demonstrated that targeting metastatic tumor sites by hADSC expressing IP-10 could reduce melanoma tumor growth and lung metastasis. Keywords: Melanoma Metastasis Human adipose derived mesenchymal stem cells CXCL10

Item Type: Article
Additional Information: cited By 1
Subjects: Biochemistry, Genetics and Molecular Biology
Divisions: Faculty of Medicine > Basic Sciences > Applied Cell Sciences
Depositing User: ART . editor
Date Deposited: 27 Feb 2019 13:03
Last Modified: 27 Feb 2019 13:03
URI: http://eprints.kaums.ac.ir/id/eprint/3399

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