The Therapeutic Potential of Human Adipose-Derived Mesenchymal Stem Cells Producing Cxcl10 in a Mouse Melanoma Lung Metastasis Model Publisher Pubmed



Mirzaei H¹ ; Salehi H² ; Oskuee RK¹ ; Mohammadpour A³ ; Mirzaei HR^{4, 5} ; Sharifi MR⁶ ; Salarinia R⁷ ; Darani HY⁸ ; Mokhtari M⁹ ; Masoudifar A¹⁰ ; Sahebkar A^{11, 12} ; Salehi R⁶ ; Jaafari MR^{13, 14}
Source: Cancer Letters Published:2018

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. © 2018 Elsevier B.V.