Scalable culture strategies for the expansion of patient-derived cancer stem cell lines
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/96255 |
Resumo: | Cancer stem cells (CSCs) have recently raised great interest as a promising biological system for designing effective cancer therapies. The scarcity of CSCs in vivo and the consequent low numbers obtained from biopsies represent a major hurdle to the development of such strategies. It is therefore necessary to design robust scalable methods to enable efficient expansion of bona fide CSCs in vitro. Here, we evaluated the applicability of computer-controlled bioreactors combined with 3D aggregate culture and microcarrier technology, widely used in stem cell bioprocessing, for the expansion and enrichment of CSCs isolated from different types of solid tumors—colorectal cancer (CRC) and non-small-cell lung cancer (NSCLC) from two patients. Results show that these culture strategies improved cell expansion and CSC enrichment. Both patient-derived CSC lines were able to grow on microcarriers, the best results being achieved for PPlus 102-L, Pro-F 102-L, Fact 102-L, and CGEN 102-L beads (5-fold and 40-fold increase in total cell concentration for CRC and NSCLC cells, respectively, in 6 days). As for 3D aggregate culture strategy, the cell proliferation profile was donor dependent. NSCLC cells were the only cells able to form aggregates and proliferate, and the flat-bottom bioreactor vessel equipped with a trapezoid-shaped paddle impeller was the most efficient configuration for cell growth (21-fold increase in cell concentration achieved in 8 days). Serum-free medium promotes CSC enrichment in both 3D aggregate and microcarrier cultures. The protocols developed herein for CSC expansion have the potential to be transferred to clinical and industrial settings, providing key insights to guide bioprocess design towards the production of enriched CSC cultures in higher quantity and improved quality. |
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Scalable culture strategies for the expansion of patient-derived cancer stem cell linesMolecular BiologyCell BiologySDG 3 - Good Health and Well-beingCancer stem cells (CSCs) have recently raised great interest as a promising biological system for designing effective cancer therapies. The scarcity of CSCs in vivo and the consequent low numbers obtained from biopsies represent a major hurdle to the development of such strategies. It is therefore necessary to design robust scalable methods to enable efficient expansion of bona fide CSCs in vitro. Here, we evaluated the applicability of computer-controlled bioreactors combined with 3D aggregate culture and microcarrier technology, widely used in stem cell bioprocessing, for the expansion and enrichment of CSCs isolated from different types of solid tumors—colorectal cancer (CRC) and non-small-cell lung cancer (NSCLC) from two patients. Results show that these culture strategies improved cell expansion and CSC enrichment. Both patient-derived CSC lines were able to grow on microcarriers, the best results being achieved for PPlus 102-L, Pro-F 102-L, Fact 102-L, and CGEN 102-L beads (5-fold and 40-fold increase in total cell concentration for CRC and NSCLC cells, respectively, in 6 days). As for 3D aggregate culture strategy, the cell proliferation profile was donor dependent. NSCLC cells were the only cells able to form aggregates and proliferate, and the flat-bottom bioreactor vessel equipped with a trapezoid-shaped paddle impeller was the most efficient configuration for cell growth (21-fold increase in cell concentration achieved in 8 days). Serum-free medium promotes CSC enrichment in both 3D aggregate and microcarrier cultures. The protocols developed herein for CSC expansion have the potential to be transferred to clinical and industrial settings, providing key insights to guide bioprocess design towards the production of enriched CSC cultures in higher quantity and improved quality.Instituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNSerra, Ana TeresaSerra, MargaridaSilva, Ana Carina Santos Ferreira daBrckalo, TamaraSeshire, AnitaBrito, CatarinaWolf, MichaelAlves, Paula M.2020-04-15T22:37:13Z2019-01-012019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/96255eng1687-9678PURE: 17681682https://doi.org/10.1155/2019/8347595info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:43:58Zoai:run.unl.pt:10362/96255Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:38:31.844245Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Scalable culture strategies for the expansion of patient-derived cancer stem cell lines |
title |
Scalable culture strategies for the expansion of patient-derived cancer stem cell lines |
spellingShingle |
Scalable culture strategies for the expansion of patient-derived cancer stem cell lines Serra, Ana Teresa Molecular Biology Cell Biology SDG 3 - Good Health and Well-being |
title_short |
Scalable culture strategies for the expansion of patient-derived cancer stem cell lines |
title_full |
Scalable culture strategies for the expansion of patient-derived cancer stem cell lines |
title_fullStr |
Scalable culture strategies for the expansion of patient-derived cancer stem cell lines |
title_full_unstemmed |
Scalable culture strategies for the expansion of patient-derived cancer stem cell lines |
title_sort |
Scalable culture strategies for the expansion of patient-derived cancer stem cell lines |
author |
Serra, Ana Teresa |
author_facet |
Serra, Ana Teresa Serra, Margarida Silva, Ana Carina Santos Ferreira da Brckalo, Tamara Seshire, Anita Brito, Catarina Wolf, Michael Alves, Paula M. |
author_role |
author |
author2 |
Serra, Margarida Silva, Ana Carina Santos Ferreira da Brckalo, Tamara Seshire, Anita Brito, Catarina Wolf, Michael Alves, Paula M. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Instituto de Tecnologia Química e Biológica António Xavier (ITQB) RUN |
dc.contributor.author.fl_str_mv |
Serra, Ana Teresa Serra, Margarida Silva, Ana Carina Santos Ferreira da Brckalo, Tamara Seshire, Anita Brito, Catarina Wolf, Michael Alves, Paula M. |
dc.subject.por.fl_str_mv |
Molecular Biology Cell Biology SDG 3 - Good Health and Well-being |
topic |
Molecular Biology Cell Biology SDG 3 - Good Health and Well-being |
description |
Cancer stem cells (CSCs) have recently raised great interest as a promising biological system for designing effective cancer therapies. The scarcity of CSCs in vivo and the consequent low numbers obtained from biopsies represent a major hurdle to the development of such strategies. It is therefore necessary to design robust scalable methods to enable efficient expansion of bona fide CSCs in vitro. Here, we evaluated the applicability of computer-controlled bioreactors combined with 3D aggregate culture and microcarrier technology, widely used in stem cell bioprocessing, for the expansion and enrichment of CSCs isolated from different types of solid tumors—colorectal cancer (CRC) and non-small-cell lung cancer (NSCLC) from two patients. Results show that these culture strategies improved cell expansion and CSC enrichment. Both patient-derived CSC lines were able to grow on microcarriers, the best results being achieved for PPlus 102-L, Pro-F 102-L, Fact 102-L, and CGEN 102-L beads (5-fold and 40-fold increase in total cell concentration for CRC and NSCLC cells, respectively, in 6 days). As for 3D aggregate culture strategy, the cell proliferation profile was donor dependent. NSCLC cells were the only cells able to form aggregates and proliferate, and the flat-bottom bioreactor vessel equipped with a trapezoid-shaped paddle impeller was the most efficient configuration for cell growth (21-fold increase in cell concentration achieved in 8 days). Serum-free medium promotes CSC enrichment in both 3D aggregate and microcarrier cultures. The protocols developed herein for CSC expansion have the potential to be transferred to clinical and industrial settings, providing key insights to guide bioprocess design towards the production of enriched CSC cultures in higher quantity and improved quality. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-01-01 2019-01-01T00:00:00Z 2020-04-15T22:37:13Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/96255 |
url |
http://hdl.handle.net/10362/96255 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1687-9678 PURE: 17681682 https://doi.org/10.1155/2019/8347595 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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