3D culture of functional human iPSC-derived hepatocytes using a core-shell microfiber

Nagata, Shogo; Ozawa, Fumisato; Nie, Minghao; Takeuchi, Shoji

doi:10.1371/journal.pone.0234441

“…al. has paved the way for this kind of development using spheroids 12 , and we also have already succeeded in developing cell fibers for different types of human-derived cells [23][24][25]42…”

Section: Discussionmentioning

confidence: 99%

In Vitro Proliferation and Long-Term Preservation of Functional Primary Rat Hepatocytes in Cell Fibers

Mazari-Arrighi

¹

,

Okitsu²,

Teramae³

et al. 2021

Preprint

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Primary hepatocytes are essential cellular resource for drug screening and medical transplantation. Since culture systems for them have already succeeded in reconstituting the biomimetic microenvironment, acquiring additional capabilities both to expand primary hepatocytes and to handle them easily would be expected as progress to the next stage. This paper describes a culture system for primary rat hepatocytes that is equipped with scalability and handleability relying on cell fiber technology. Cell fibers are cell-laden core-shell hydrogel microfibers; in the core regions, cells are embedded in extracellular matrix proteins, cultured three-dimensionally, and exposed to soluble growth factors in the culture medium through the hydrogel shells. By encapsulating primary rat hepatocytes within cell fibers, we first demonstrated they increase in number while keeping their viability and their hepatic specific functions for up to thirty days of subsequent culture. Then, we demonstrated the potency of the primary rat hepatocytes that proliferate in cell fibers not only as cell-based sensors to detect drugs that damage hepatic functions and hepatocellular processes but also as transplants to improve the plasma albumin concentrations of congenital analbuminemia. Therefore, our culture system could serve for innovating strategies and promising developments in applying primary hepatocytes to both pharmaceutical and medical fields.

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“…al. has paved the way for this kind of development using spheroids 12 , and we also have already succeeded in developing cell bers for different types of human-derived cells [23][24][25]42 Material And Methods…”

Section: Discussionmentioning

confidence: 99%

In Vitro Proliferation and Long-Term Preservation of Functional Primary Rat Hepatocytes in Cell Fibers

Mazari-Arrighi

¹

,

Okitsu

²

,

Teramae

³

et al. 2021

Preprint

Self Cite

0

View full text Add to dashboard Cite

Primary hepatocytes are essential cellular resource for drug screening and medical transplantation. Since culture systems for them have already succeeded in reconstituting the biomimetic microenvironment, acquiring additional capabilities both to expand primary hepatocytes and to handle them easily would be expected as progress to the next stage. This paper describes a culture system for primary rat hepatocytes that is equipped with scalability and handleability relying on cell fiber technology. Cell fibers are cell-laden core-shell hydrogel microfibers; in the core regions, cells are embedded in extracellular matrix proteins, cultured three-dimensionally, and exposed to soluble growth factors in the culture medium through the hydrogel shells. By encapsulating primary rat hepatocytes within cell fibers, we first demonstrated they increase in number while keeping their viability and their hepatic specific functions for up to thirty days of subsequent culture. Then, we demonstrated the potency of the primary rat hepatocytes that proliferate in cell fibers not only as cell-based sensors to detect drugs that damage hepatic functions and hepatocellular processes but also as transplants to improve the plasma albumin concentrations of congenital analbuminemia. Therefore, our culture system could serve for innovating strategies and promising developments in applying primary hepatocytes to both pharmaceutical and medical fields.

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“…(b) Non-cancerous disease models and regenerative medicine Preclinical models for a large spectrum of pathological conditions also take advantage of the elaboration of cellularized materials. Indicatively, corneal stromal disease models can be obtained using collagen bioinks [266], hydrogels can serve as Alzheimer's disease models [267], and liver toxicity can be assessed through core-shell hydrogel fibres [268]. In addition, the field of regenerative medicine exploits macroporous scaffolds to repair or replace defective tissues unable to self-regenerate.…”

Section: Future Trends I: Cellularized Materials In Tissue Engineering (A) Healthy Tissue Modelsmentioning

confidence: 99%

Colonization versus encapsulation in cell-laden materials design: porosity and process biocompatibility determine cellularization pathways

Parisi

¹

,

Qin

²

,

Fernandes

³

2021

Phil. Trans. R. Soc. A.

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Seeding materials with living cells has been—and still is—one of the most promising approaches to reproduce the complexity and the functionality of living matter. The strategies to associate living cells with materials are limited to cell encapsulation and colonization, however, the requirements for these two approaches have been seldom discussed systematically. Here we propose a simple two-dimensional map based on materials' pore size and the cytocompatibility of their fabrication process to draw, for the first time, a guide to building cellularized materials. We believe this approach may serve as a straightforward guideline to design new, more relevant materials, able to seize the complexity and the function of biological materials. This article is part of the theme issue ‘Bio-derived and bioinspired sustainable advanced materials for emerging technologies (part 1)’.

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3D culture of functional human iPSC-derived hepatocytes using a core-shell microfiber

Cited by 21 publications

References 28 publications

In Vitro Proliferation and Long-Term Preservation of Functional Primary Rat Hepatocytes in Cell Fibers

In Vitro Proliferation and Long-Term Preservation of Functional Primary Rat Hepatocytes in Cell Fibers

In Vitro Proliferation and Long-Term Preservation of Functional Primary Rat Hepatocytes in Cell Fibers

Colonization versus encapsulation in cell-laden materials design: porosity and process biocompatibility determine cellularization pathways

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