Using the Microwell-mesh to culture microtissues in vitro and as a carrier to implant microtissues in vivo into mice

Abstract Prostate cancer (PCa) patient-derived xenografts (PDXs) are commonly propagated by serial transplantation of “pieces” of tumour in mice, but the cellular composition of pieces is not standardised. Herein, we optimised a microwell platform, the Microwell-mesh, to aggregate precise numbers of...

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Autores principales:	Melissa E. Monterosso, Kathryn Futrega, William B. Lott, Ian Vela, Elizabeth D. Williams, Michael R. Doran
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2f5eb33aec0547329c75ee64f3601dbc
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spelling	oai:doaj.org-article:2f5eb33aec0547329c75ee64f3601dbc2021-12-02T13:20:13ZUsing the Microwell-mesh to culture microtissues in vitro and as a carrier to implant microtissues in vivo into mice10.1038/s41598-021-84154-42045-2322https://doaj.org/article/2f5eb33aec0547329c75ee64f3601dbc2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84154-4https://doaj.org/toc/2045-2322Abstract Prostate cancer (PCa) patient-derived xenografts (PDXs) are commonly propagated by serial transplantation of “pieces” of tumour in mice, but the cellular composition of pieces is not standardised. Herein, we optimised a microwell platform, the Microwell-mesh, to aggregate precise numbers of cells into arrays of microtissues, and then implanted the Microwell-mesh into NOD-scid IL2γ−/− (NSG) mice to study microtissue growth. First, mesh pore size was optimised using microtissues assembled from bone marrow-derived stromal cells, with mesh opening dimensions of 100×100 μm achieving superior microtissue vascularisation relative to mesh with 36×36 μm mesh openings. The optimised Microwell-mesh was used to assemble and implant PCa cell microtissue arrays (hereafter microtissues formed from cancer cells are referred to as microtumours) into mice. PCa cells were enriched from three different PDX lines, LuCaP35, LuCaP141, and BM18. 3D microtumours showed greater in vitro viability than 2D cultures, but neither proliferated. Microtumours were successfully established in mice 81% (57 of 70), 67% (4 of 6), 76% (19 of 25) for LuCaP35, LuCaP141, and BM18 PCa cells, respectively. Microtumour growth was tracked using live animal imaging for size or bioluminescence signal. If augmented with further imaging advances and cell bar coding, this microtumour model could enable greater resolution of PCa PDX drug response, and lead to the more efficient use of animals. The concept of microtissue assembly in the Microwell-mesh, and implantation in vivo may also have utility in implantation of islets, hair follicles or other organ-specific cells that self-assemble into 3D structures, providing an important bridge between in vitro assembly of mini-organs and in vivo implantation.Melissa E. MonterossoKathryn FutregaWilliam B. LottIan VelaElizabeth D. WilliamsMichael R. DoranNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Melissa E. Monterosso Kathryn Futrega William B. Lott Ian Vela Elizabeth D. Williams Michael R. Doran Using the Microwell-mesh to culture microtissues in vitro and as a carrier to implant microtissues in vivo into mice
description	Abstract Prostate cancer (PCa) patient-derived xenografts (PDXs) are commonly propagated by serial transplantation of “pieces” of tumour in mice, but the cellular composition of pieces is not standardised. Herein, we optimised a microwell platform, the Microwell-mesh, to aggregate precise numbers of cells into arrays of microtissues, and then implanted the Microwell-mesh into NOD-scid IL2γ−/− (NSG) mice to study microtissue growth. First, mesh pore size was optimised using microtissues assembled from bone marrow-derived stromal cells, with mesh opening dimensions of 100×100 μm achieving superior microtissue vascularisation relative to mesh with 36×36 μm mesh openings. The optimised Microwell-mesh was used to assemble and implant PCa cell microtissue arrays (hereafter microtissues formed from cancer cells are referred to as microtumours) into mice. PCa cells were enriched from three different PDX lines, LuCaP35, LuCaP141, and BM18. 3D microtumours showed greater in vitro viability than 2D cultures, but neither proliferated. Microtumours were successfully established in mice 81% (57 of 70), 67% (4 of 6), 76% (19 of 25) for LuCaP35, LuCaP141, and BM18 PCa cells, respectively. Microtumour growth was tracked using live animal imaging for size or bioluminescence signal. If augmented with further imaging advances and cell bar coding, this microtumour model could enable greater resolution of PCa PDX drug response, and lead to the more efficient use of animals. The concept of microtissue assembly in the Microwell-mesh, and implantation in vivo may also have utility in implantation of islets, hair follicles or other organ-specific cells that self-assemble into 3D structures, providing an important bridge between in vitro assembly of mini-organs and in vivo implantation.
format	article
author	Melissa E. Monterosso Kathryn Futrega William B. Lott Ian Vela Elizabeth D. Williams Michael R. Doran
author_facet	Melissa E. Monterosso Kathryn Futrega William B. Lott Ian Vela Elizabeth D. Williams Michael R. Doran
author_sort	Melissa E. Monterosso
title	Using the Microwell-mesh to culture microtissues in vitro and as a carrier to implant microtissues in vivo into mice
title_short	Using the Microwell-mesh to culture microtissues in vitro and as a carrier to implant microtissues in vivo into mice
title_full	Using the Microwell-mesh to culture microtissues in vitro and as a carrier to implant microtissues in vivo into mice
title_fullStr	Using the Microwell-mesh to culture microtissues in vitro and as a carrier to implant microtissues in vivo into mice
title_full_unstemmed	Using the Microwell-mesh to culture microtissues in vitro and as a carrier to implant microtissues in vivo into mice
title_sort	using the microwell-mesh to culture microtissues in vitro and as a carrier to implant microtissues in vivo into mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2f5eb33aec0547329c75ee64f3601dbc
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Using the Microwell-mesh to culture microtissues in vitro and as a carrier to implant microtissues in vivo into mice

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