Reshaping in vitro Models of Breast Tissue: Integration of Stromal and Parenchymal Compartments in 3D Printed Hydrogels

Detalhes bibliográficos
Autor(a) principal: Silva, PB
Data de Publicação: 2020
Outros Autores: Coelho, M, Bidarra, SJ, Neves, SC, Barrias, CC
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/10216/143481
Resumo: Breast tissue consists of an epithelial parenchyma embedded in stroma, of heterogeneous and complex composition, undergoing several morphological and functional alterations throughout females' lifespan. Improved knowledge on the crosstalk between parenchymal and stromal mammary cells should provide important insights on breast tissue dynamics, both under healthy and diseased states. Here, we describe an advanced 3D in vitro model of breast tissue, combining multiple components, namely stromal cells and their extracellular matrix (ECM), as well as parenchymal epithelial cells, in a hybrid system. To build the model, porous scaffolds were produced by extrusion 3D printing of peptide-modified alginate hydrogels, and then populated with human mammary fibroblasts. Seeded fibroblasts were able to adhere, spread and produce endogenous ECM, providing adequate coverage of the scaffold surface, without obstructing the pores. On a second stage, a peptide-modified alginate pre-gel laden with mammary gland epithelial cells was used to fill the scaffold's pores, forming a hydrogel in situ by ionic crosslinking. Throughout time, epithelial cells formed prototypical mammary acini-like structures, in close proximity with fibroblasts and their ECM. This generated a heterotypic 3D model that partially recreates both stromal and parenchymal compartments of breast tissue, promoting cell-cell and cell-matrix crosstalk. Furthermore, the hybrid system could be easily dissolved for cell recovery and subsequent analysis by standard cellular/molecular assays. In particular, we show that retrieved cell populations could be discriminated by flow cytometry using cell-type specific markers. This integrative 3D model stands out as a promising in vitro platform for studying breast stroma-parenchyma interactions, both under physiological and pathological settings.
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spelling Reshaping in vitro Models of Breast Tissue: Integration of Stromal and Parenchymal Compartments in 3D Printed Hydrogels3D model3D printingepithelial morphogenesishydrogelparenchymastromatissue engineeringBreast tissue consists of an epithelial parenchyma embedded in stroma, of heterogeneous and complex composition, undergoing several morphological and functional alterations throughout females' lifespan. Improved knowledge on the crosstalk between parenchymal and stromal mammary cells should provide important insights on breast tissue dynamics, both under healthy and diseased states. Here, we describe an advanced 3D in vitro model of breast tissue, combining multiple components, namely stromal cells and their extracellular matrix (ECM), as well as parenchymal epithelial cells, in a hybrid system. To build the model, porous scaffolds were produced by extrusion 3D printing of peptide-modified alginate hydrogels, and then populated with human mammary fibroblasts. Seeded fibroblasts were able to adhere, spread and produce endogenous ECM, providing adequate coverage of the scaffold surface, without obstructing the pores. On a second stage, a peptide-modified alginate pre-gel laden with mammary gland epithelial cells was used to fill the scaffold's pores, forming a hydrogel in situ by ionic crosslinking. Throughout time, epithelial cells formed prototypical mammary acini-like structures, in close proximity with fibroblasts and their ECM. This generated a heterotypic 3D model that partially recreates both stromal and parenchymal compartments of breast tissue, promoting cell-cell and cell-matrix crosstalk. Furthermore, the hybrid system could be easily dissolved for cell recovery and subsequent analysis by standard cellular/molecular assays. In particular, we show that retrieved cell populations could be discriminated by flow cytometry using cell-type specific markers. This integrative 3D model stands out as a promising in vitro platform for studying breast stroma-parenchyma interactions, both under physiological and pathological settings.Frontiers Media20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/143481eng2296-418510.3389/fbioe.2020.00494Silva, PBCoelho, MBidarra, SJNeves, SCBarrias, CCinfo: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:RCAAP2023-11-29T15:14:25Zoai:repositorio-aberto.up.pt:10216/143481Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:18:44.906754Repositório 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 Reshaping in vitro Models of Breast Tissue: Integration of Stromal and Parenchymal Compartments in 3D Printed Hydrogels
title Reshaping in vitro Models of Breast Tissue: Integration of Stromal and Parenchymal Compartments in 3D Printed Hydrogels
spellingShingle Reshaping in vitro Models of Breast Tissue: Integration of Stromal and Parenchymal Compartments in 3D Printed Hydrogels
Silva, PB
3D model
3D printing
epithelial morphogenesis
hydrogel
parenchyma
stroma
tissue engineering
title_short Reshaping in vitro Models of Breast Tissue: Integration of Stromal and Parenchymal Compartments in 3D Printed Hydrogels
title_full Reshaping in vitro Models of Breast Tissue: Integration of Stromal and Parenchymal Compartments in 3D Printed Hydrogels
title_fullStr Reshaping in vitro Models of Breast Tissue: Integration of Stromal and Parenchymal Compartments in 3D Printed Hydrogels
title_full_unstemmed Reshaping in vitro Models of Breast Tissue: Integration of Stromal and Parenchymal Compartments in 3D Printed Hydrogels
title_sort Reshaping in vitro Models of Breast Tissue: Integration of Stromal and Parenchymal Compartments in 3D Printed Hydrogels
author Silva, PB
author_facet Silva, PB
Coelho, M
Bidarra, SJ
Neves, SC
Barrias, CC
author_role author
author2 Coelho, M
Bidarra, SJ
Neves, SC
Barrias, CC
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Silva, PB
Coelho, M
Bidarra, SJ
Neves, SC
Barrias, CC
dc.subject.por.fl_str_mv 3D model
3D printing
epithelial morphogenesis
hydrogel
parenchyma
stroma
tissue engineering
topic 3D model
3D printing
epithelial morphogenesis
hydrogel
parenchyma
stroma
tissue engineering
description Breast tissue consists of an epithelial parenchyma embedded in stroma, of heterogeneous and complex composition, undergoing several morphological and functional alterations throughout females' lifespan. Improved knowledge on the crosstalk between parenchymal and stromal mammary cells should provide important insights on breast tissue dynamics, both under healthy and diseased states. Here, we describe an advanced 3D in vitro model of breast tissue, combining multiple components, namely stromal cells and their extracellular matrix (ECM), as well as parenchymal epithelial cells, in a hybrid system. To build the model, porous scaffolds were produced by extrusion 3D printing of peptide-modified alginate hydrogels, and then populated with human mammary fibroblasts. Seeded fibroblasts were able to adhere, spread and produce endogenous ECM, providing adequate coverage of the scaffold surface, without obstructing the pores. On a second stage, a peptide-modified alginate pre-gel laden with mammary gland epithelial cells was used to fill the scaffold's pores, forming a hydrogel in situ by ionic crosslinking. Throughout time, epithelial cells formed prototypical mammary acini-like structures, in close proximity with fibroblasts and their ECM. This generated a heterotypic 3D model that partially recreates both stromal and parenchymal compartments of breast tissue, promoting cell-cell and cell-matrix crosstalk. Furthermore, the hybrid system could be easily dissolved for cell recovery and subsequent analysis by standard cellular/molecular assays. In particular, we show that retrieved cell populations could be discriminated by flow cytometry using cell-type specific markers. This integrative 3D model stands out as a promising in vitro platform for studying breast stroma-parenchyma interactions, both under physiological and pathological settings.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.uri.fl_str_mv https://hdl.handle.net/10216/143481
url https://hdl.handle.net/10216/143481
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2296-4185
10.3389/fbioe.2020.00494
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dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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