Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: a new biosafety insight

dc.contributor.authorBruna, Flavia
dc.contributor.authorPlaza, Anita
dc.contributor.authorArango, Martha
dc.contributor.authorEspinoza, Iris
dc.contributor.authorConget, Paulette
dc.date.accessioned2022-06-03T20:56:04Z
dc.date.available2022-06-03T20:56:04Z
dc.date.issued2018
dc.description.abstractBackground: Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal cells currently tested for multiple therapeutic purposes. Their potential to home into tumors, to secrete trophic/vasculogenic factors, and to suppress immune response raises questions regarding their biosafety. Our aim was to evaluate whether systemically administered allogeneic MSCs modify the natural progression of precancerous lesions and whether their putative effect depends on cancer stage and/or cell dose. Methods: Oral squamous cell carcinoma (OSCC) was induced in Syrian golden hamsters by topical application of 7,12-dimethylbenz[a]anthracene in one buccal pouch. At hyperplasia, dysplasia, or papilloma stage, animals received intracardially the vehicle or 0.7 × 106 , 7 × 106 , or 21 × 106 allogeneic bone marrow-derived MSCs/kg. OSCC progression was assessed according to the presence of erythroplakia and leukoplakia, extent of inflammation and vascularization, and appearance, volume, and staging of tumors. Also, the homing of donor cells was studied. Results: Precancerous lesions progressed from hyperplasia to dysplasia in 2 weeks, from dysplasia to papilloma in 3 weeks, and from papilloma to carcinoma in 4 weeks. This time course was unmodified by the systemic administration of MSCs at hyperplasia or dysplasia stages. When MSCs were administered at papilloma stage, lesions did not progress to carcinoma stage. Tumors developed in hamsters receiving 0.7 × 106 or 7 × 106 MSCs/kg at hyperplasia stage were significantly smaller than those found in control animals (25 ± 4 or 23 ± 4 mm3 versus 72 ± 19 mm3 , p < 0.05). Similar results were obtained when 0.7 × 106 , 7 × 106 , or 21 × 106 MSCs/kg were administered at papilloma stage (44 ± 15, 28 ± 7, or 28 ± 5 mm3 versus 104 ± 26 mm3 , p < 0.05). For dysplasia stage, only the lower concentration of MSCs reached statistical significance (21 ± 9 mm3 versus 94 ± 39 mm3 , p < 0.05). Animals receiving 21 × 106 MSCs/kg at hyperplasia stage developed tumors larger than those found in animals that received the vehicle (147 ± 47 mm3 versus 72 ± 19 mm3 , p < 0.05). Donor cells were rarely found in precancerous lesions. Conclusions: Systemically administered allogeneic MSCs do not aggravate the progression of precancerous lesions. Moreover, they preclude cancer progression and tumor growth.es
dc.description.versionVersión Publicadaes
dc.identifier.citationBruna F, Plaza A, Arango M, Espinoza I, Conget P. Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: a new biosafety insight. Stem Cell Res Ther. 2018 May 11;9(1):137. doi: 10.1186/s13287-018-0878-1.es
dc.identifier.urihttps://doi.org/10.1186/s13287-018-0878-1es
dc.identifier.urihttp://hdl.handle.net/11447/6185
dc.language.isoenes
dc.subjectMesenchymal stem cellses
dc.subjectMultipotent stromal cellses
dc.subjectOral squamous cell carcinomaes
dc.subjectSystemic administrationes
dc.subjectCancer progressiones
dc.subjectBiosafetyes
dc.titleSystemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: a new biosafety insightes
dc.typeArticlees
dcterms.sourceStem Cell Research & Therapyes

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