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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2021.tde-19082021-101815
Document
Author
Full name
Fernanda Carrilho de Menezes
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2020
Supervisor
Committee
Festa Neto, Cyro (President)
Oliveira Filho, Jayme de
Aoki, Valeria
Tovo Filho, Reynaldo
Title in Portuguese
Efeito da terapia celular com células-tronco mesenquimais em melanoma murino B16-F10
Keywords in Portuguese
Apoptose.
Células-tronco mesenquimais
Imunomodulação
melanoma
Tumor
Abstract in Portuguese
O melanoma cutâneo (MC) é uma transformação maligna dos melanócitos, células derivadas da crista neural produtoras de melanina que podem ser encontradas principalmente na epiderme basal e nos folículos capilares, as taxas de mortalidade são altas devido à agressividade do tumor, e a incidência varia entre os países. O presente estudo objetivou avaliar os efeitos antitumorais e imunomoduladores de células-tronco mesenquimais (CTM) obtidas da medula óssea no tratamento do melanoma dorsal B16-F10. As CTM foram obtidas da medula óssea de camundongos isogênicos C57BL/6J, caracterizadas e inoculadas por duas vias, intratumoral (it) e endovenosa (ev). O perfil hematológico, marcadores de expressão e receptores, fases do ciclo celular e potencial elétrico mitocondrial foram avaliados por citometria de fluxo. A massa tumoral dorsal apresentou redução significativa após o tratamento pelas duas vias de administração, com efeito significativo pela via intravenosa. CTM apresentou potencial imunomodulador e não induziu aumento nos marcadores envolvidos no controle e progressão tumoral. O número de células na fase sub-G1 aumentou significativamente após os tratamentos em comparação com o grupo controle. A porcentagem de células nas fases G0/G1, S e G2/M diminuíram apenas para o tratamento com grupo (it) apresentando redução significativa. O grupo (it) apresentou diminuição significativa na fase G2/M. O tratamento com CTM proporcionou redução significativa no percentual de células tumorais metabolicamente ativas, demonstrando seu efeito intrínseco no controle da proliferação celular. Em relação ao mecanismo de morte celular, as CTM modulam a expressão de proteínas envolvidas na regulação do ciclo celular, receptores de angiogênese e proteínas pró-apoptóticas por vias intrínsecas e extrínsecas. Portanto, ouso de CTM indiferenciadas, administradas por via intratumoral e endovenosa, épossivelmente um tratamento promissor para o melanoma.
Title in English
Antitumor effect of cell therapy with mesenchymal stem cells on murine melanoma B16-F10
Keywords in English
Apoptosis
Immunomodulatory
Melanoma
Mesenchymal stem cells
Tumor
Abstract in English
Cutaneous melanoma (MC) is a malignant transformation of melanocytes, cells derived from the melanin-producing neural crest that can be found mainly in the basal epidermis and hair follicles, mortality rates are high due to the aggressiveness of the tumor, and the incidence varies between countries. The present study aimed to evaluate the antitumor and immunomodulatory effects of mesenchymal stem cells (MSC) obtained from bone marrow in the treatment of dorsal melanoma B16-F10. MSCs were obtained from the bone marrow of isogenic C57BL/6J mice, characterized and inoculated by two routes, intratumoral (it) and intravenous (ev). The hematological profile, expression markers and receptors, phases of the cell cycle and mitochondrial electrical potential were evaluated by flow cytometry. The dorsal tumor mass showed a significant reduction after treatment by the two routes of administration, with significant effect by the intravenous route. MSC showed immunomodulatory potential and did not induce an increase in the markers involved in tumor progression and control. The number of cells in the sub-G1 phase increased significantly after treatments compared to the control group. The percentage of cells in phases G0/G1, S, and G2/M decreased only for treatment with a group (it), presenting a significant reduction. The (it) group showed a significant decrease in the G2/M phase. Treatment with MSC provided a significant reduction in the percentage of metabolically active tumor cells, demonstrating its intrinsic effect in the control of cell proliferation. Regarding the mechanism of cell death, MSC modulate the expression of proteins involved in the regulation of the cell cycle, angiogenesis receptors, and pro-apoptotic proteins by intrinsic and extrinsic routes. Therefore, the use of undifferentiated MSC, administered intratumorally, and intravenously, is possibly a promising treatment for melanoma
 
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Publishing Date
2021-08-19
 
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