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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 HR4, 5 ; Sharifi MR6 ; Salarinia R7 ; Darani HY8 ; Mokhtari M9 ; Masoudifar A10 ; Sahebkar A11, 12 ; Salehi R6 ; Jaafari MR13, 14
Authors
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Authors Affiliations
  1. 1. Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  2. 2. Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Faculty of Nursing and Midwifery, Gonabad University of Medical Sciences, Gonabad, Iran
  4. 4. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Clinical Laboratory Sciences, School of Allied Medical Sciences, Kashan University of Medical Sciences, Kashan, Iran
  6. 6. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
  7. 7. Department of Medical Biotechnology, School of Medicine, North Khorasan University of Medical Sciences, Bojnourd, Iran
  8. 8. Department of Medical Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  9. 9. Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  10. 10. Department of Molecular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
  11. 11. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
  12. 12. Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
  13. 13. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
  14. 14. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

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.
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