Trabecular bone organoids: a micron-scale ‘humanised’ prototype designed to study the effects of microgravity and degeneration

Abstract Bone is a highly responsive organ, which continuously adapts to the environment it is subjected to in order to withstand metabolic demands. These events are difficult to study in this particular tissue in vivo, due to its rigid, mineralised structure and inaccessibility of the cellular comp...

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Autores principales:	Alexandra Iordachescu, Erik A. B. Hughes, Stephan Joseph, Eric J. Hill, Liam M. Grover, Anthony D. Metcalfe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Biotechnology TP248.13-248.65 Physiology QP1-981
Acceso en línea:	https://doaj.org/article/92d0f1bac35a4b89b446ed691ff37888
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spelling	oai:doaj.org-article:92d0f1bac35a4b89b446ed691ff378882021-12-02T14:59:08ZTrabecular bone organoids: a micron-scale ‘humanised’ prototype designed to study the effects of microgravity and degeneration10.1038/s41526-021-00146-82373-8065https://doaj.org/article/92d0f1bac35a4b89b446ed691ff378882021-05-01T00:00:00Zhttps://doi.org/10.1038/s41526-021-00146-8https://doaj.org/toc/2373-8065Abstract Bone is a highly responsive organ, which continuously adapts to the environment it is subjected to in order to withstand metabolic demands. These events are difficult to study in this particular tissue in vivo, due to its rigid, mineralised structure and inaccessibility of the cellular component located within. This manuscript presents the development of a micron-scale bone organoid prototype, a concept that can allow the study of bone processes at the cell-tissue interface. The model is constructed with a combination of primary female osteoblastic and osteoclastic cells, seeded onto femoral head micro-trabeculae, where they recapitulate relevant phenotypes and functions. Subsequently, constructs are inserted into a simulated microgravity bioreactor (NASA-Synthecon) to model a pathological state of reduced mechanical stimulation. In these constructs, we detected osteoclastic bone resorption sites, which were different in morphology in the simulated microgravity group compared to static controls. Once encapsulated in human fibrin and exposed to analogue microgravity for 5 days, masses of bone can be observed being lost from the initial structure, allowing to simulate the bone loss process further. Constructs can function as multicellular, organotypic units. Large osteocytic projections and tubular structures develop from the initial construct into the matrix at the millimetre scale. Micron-level fragments from the initial bone structure are detected travelling along these tubules and carried to sites distant from the native structure, where new matrix formation is initiated. We believe this model allows the study of fine-level physiological processes, which can shed light into pathological bone loss and imbalances in bone remodelling.Alexandra IordachescuErik A. B. HughesStephan JosephEric J. HillLiam M. GroverAnthony D. MetcalfeNature PortfolioarticleBiotechnologyTP248.13-248.65PhysiologyQP1-981ENnpj Microgravity, Vol 7, Iss 1, Pp 1-21 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biotechnology TP248.13-248.65 Physiology QP1-981
spellingShingle	Biotechnology TP248.13-248.65 Physiology QP1-981 Alexandra Iordachescu Erik A. B. Hughes Stephan Joseph Eric J. Hill Liam M. Grover Anthony D. Metcalfe Trabecular bone organoids: a micron-scale ‘humanised’ prototype designed to study the effects of microgravity and degeneration
description	Abstract Bone is a highly responsive organ, which continuously adapts to the environment it is subjected to in order to withstand metabolic demands. These events are difficult to study in this particular tissue in vivo, due to its rigid, mineralised structure and inaccessibility of the cellular component located within. This manuscript presents the development of a micron-scale bone organoid prototype, a concept that can allow the study of bone processes at the cell-tissue interface. The model is constructed with a combination of primary female osteoblastic and osteoclastic cells, seeded onto femoral head micro-trabeculae, where they recapitulate relevant phenotypes and functions. Subsequently, constructs are inserted into a simulated microgravity bioreactor (NASA-Synthecon) to model a pathological state of reduced mechanical stimulation. In these constructs, we detected osteoclastic bone resorption sites, which were different in morphology in the simulated microgravity group compared to static controls. Once encapsulated in human fibrin and exposed to analogue microgravity for 5 days, masses of bone can be observed being lost from the initial structure, allowing to simulate the bone loss process further. Constructs can function as multicellular, organotypic units. Large osteocytic projections and tubular structures develop from the initial construct into the matrix at the millimetre scale. Micron-level fragments from the initial bone structure are detected travelling along these tubules and carried to sites distant from the native structure, where new matrix formation is initiated. We believe this model allows the study of fine-level physiological processes, which can shed light into pathological bone loss and imbalances in bone remodelling.
format	article
author	Alexandra Iordachescu Erik A. B. Hughes Stephan Joseph Eric J. Hill Liam M. Grover Anthony D. Metcalfe
author_facet	Alexandra Iordachescu Erik A. B. Hughes Stephan Joseph Eric J. Hill Liam M. Grover Anthony D. Metcalfe
author_sort	Alexandra Iordachescu
title	Trabecular bone organoids: a micron-scale ‘humanised’ prototype designed to study the effects of microgravity and degeneration
title_short	Trabecular bone organoids: a micron-scale ‘humanised’ prototype designed to study the effects of microgravity and degeneration
title_full	Trabecular bone organoids: a micron-scale ‘humanised’ prototype designed to study the effects of microgravity and degeneration
title_fullStr	Trabecular bone organoids: a micron-scale ‘humanised’ prototype designed to study the effects of microgravity and degeneration
title_full_unstemmed	Trabecular bone organoids: a micron-scale ‘humanised’ prototype designed to study the effects of microgravity and degeneration
title_sort	trabecular bone organoids: a micron-scale ‘humanised’ prototype designed to study the effects of microgravity and degeneration
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/92d0f1bac35a4b89b446ed691ff37888
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Trabecular bone organoids: a micron-scale ‘humanised’ prototype designed to study the effects of microgravity and degeneration

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