title: Human amniotic fluid-derived mesenchymal stem cells as therapeutic vehicles: a novel approach for the treatment of bladder cancer.
abstract: Recent studies support cell-based therapies for cancer treatment. An advantageous cell type for such therapeutic schemes are the mesenchymal stem cells (MSCs) that can be easily propagated in culture, genetically modified to express therapeutic proteins, and exhibit an innate tropism to solid tumors in vivo. Recently, we successfully isolated and expanded MSCs from second-trimester amniotic fluid (AF-MSCs). The main characteristic of AF-MSCs is their efficient and rapid expansion in vitro. Herein, we investigated the AF-MSCs tropism and capability to transport interferon beta (IFNβ) to the region of neoplasia in a bladder tumor model. To this end, we used the T24M bladder cancer cell line, previously generated from our studies, and developed a disease progression model in immunosuppressed mice, that can recapitulate the molecular events of bladder carcinogenesis. Our results documented that AF-MSCs exhibited high motility, when migrated either to T24M cells or to T24M-conditioned medium, and we further identified and studied the secreted factors which may trigger these enhanced migratory properties. Further, lentivirus-transduced AF-MSCs, expressing green fluorescent protein (GFP) or IFNβ, were intravenously administered to T24M tumor-bearing animals at multiple doses to examine their therapeutic effect. GFP- and IFNβ-AF-MSCs successfully migrated and colonized at the tumor site. Notably, significant inhibition of tumor growth as well as prolonged survival of mice were observed in the presence of IFNβ-AF-MSCs. Collectively, these results document the great potential of AF-MSCs as anti-cancer vehicles, implemented by the targeting of the tumor site and further facilitated by their high proliferation rate and expansion efficiency in culture.
authors: Cell and Gene Therapy Laboratory, Centre of Basic Research II, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece.
authors: Vasiliki
authors: V
authors: Bitsika
authors: Maria G
authors: MG
authors: Roubelakis
authors: Dimitra
authors: D
authors: Zagoura
authors: Ourania
authors: O
authors: Trohatou
authors: Manousos
authors: M
authors: Makridakis
authors: Kalliopi I
authors: KI
authors: Pappa
authors: Frank C
authors: FC
authors: Marini
authors: Antonia
authors: A
authors: Vlahou
authors: Nicholas P
authors: NP
authors: Anagnou
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016503:Drug Delivery Systems; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis / Q000097:blood / Q000494:pharmacology; D016209:Interleukin-8 / Q000502:physiology; D053208:Kaplan-Meier Estimate; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D020543:Proteome / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000097:blood / Q000494:pharmacology; D047368:Tumor Burden; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D017077:Culture Media, Conditioned; D016209:Interleukin-8; D020543:Proteome; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D049452:Green Fluorescent Proteins; D016899:Interferon-beta