Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning

Abstract Uterine factor infertility was considered incurable until recently when we reported the first successful live birth after uterus transplantation. However, risky donor surgery and immunosuppressive therapy are factors that may be avoided with bioengineering. For example, transplanted recellu...

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Autores principales:	Arvind Manikantan Padma, Laura Carrière, Frida Krokström Karlsson, Edina Sehic, Sara Bandstein, Tom Tristan Tiemann, Mihai Oltean, Min Jong Song, Mats Brännström, Mats Hellström
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/2d742bd02ed74f76a54a1c4732127536
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spelling	oai:doaj.org-article:2d742bd02ed74f76a54a1c47321275362021-12-02T15:45:19ZTowards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning10.1038/s41536-021-00136-02057-3995https://doaj.org/article/2d742bd02ed74f76a54a1c47321275362021-05-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00136-0https://doaj.org/toc/2057-3995Abstract Uterine factor infertility was considered incurable until recently when we reported the first successful live birth after uterus transplantation. However, risky donor surgery and immunosuppressive therapy are factors that may be avoided with bioengineering. For example, transplanted recellularized constructs derived from decellularized tissue restored fertility in rodent models and mandate translational studies. In this study, we decellularized whole sheep uterus with three different protocols using 0.5% sodium dodecyl sulfate, 2% sodium deoxycholate (SDC) or 2% SDC, and 1% Triton X-100. Scaffolds were then assessed for bioactivity using the dorsal root ganglion and chorioallantoic membrane assays, and we found that all the uterus scaffolds exhibited growth factor activity that promoted neurogenesis and angiogenesis. Extensive recellularization optimization was conducted using multipotent sheep fetal stem cells and we report results from the following three in vitro conditions; (a) standard cell culturing conditions, (b) constructs cultured in transwells, and (c) scaffolds preconditioned with matrix metalloproteinase 2 and 9. The recellularization efficiency was improved short-term when transwells were used compared with standard culturing conditions. However, the recellularization efficiency in scaffolds preconditioned with matrix metalloproteinases was 200–300% better than the other strategies evaluated herein, independent of decellularization protocol. Hence, a major recellularization hurdle has been overcome with the improved recellularization strategies and in vitro platforms described herein. These results are an important milestone and should facilitate the production of large bioengineered grafts suitable for future in vivo applications in the sheep, which is an essential step before considering these principles in a clinical setting.Arvind Manikantan PadmaLaura CarrièreFrida Krokström KarlssonEdina SehicSara BandsteinTom Tristan TiemannMihai OlteanMin Jong SongMats BrännströmMats HellströmNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Arvind Manikantan Padma Laura Carrière Frida Krokström Karlsson Edina Sehic Sara Bandstein Tom Tristan Tiemann Mihai Oltean Min Jong Song Mats Brännström Mats Hellström Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning
description	Abstract Uterine factor infertility was considered incurable until recently when we reported the first successful live birth after uterus transplantation. However, risky donor surgery and immunosuppressive therapy are factors that may be avoided with bioengineering. For example, transplanted recellularized constructs derived from decellularized tissue restored fertility in rodent models and mandate translational studies. In this study, we decellularized whole sheep uterus with three different protocols using 0.5% sodium dodecyl sulfate, 2% sodium deoxycholate (SDC) or 2% SDC, and 1% Triton X-100. Scaffolds were then assessed for bioactivity using the dorsal root ganglion and chorioallantoic membrane assays, and we found that all the uterus scaffolds exhibited growth factor activity that promoted neurogenesis and angiogenesis. Extensive recellularization optimization was conducted using multipotent sheep fetal stem cells and we report results from the following three in vitro conditions; (a) standard cell culturing conditions, (b) constructs cultured in transwells, and (c) scaffolds preconditioned with matrix metalloproteinase 2 and 9. The recellularization efficiency was improved short-term when transwells were used compared with standard culturing conditions. However, the recellularization efficiency in scaffolds preconditioned with matrix metalloproteinases was 200–300% better than the other strategies evaluated herein, independent of decellularization protocol. Hence, a major recellularization hurdle has been overcome with the improved recellularization strategies and in vitro platforms described herein. These results are an important milestone and should facilitate the production of large bioengineered grafts suitable for future in vivo applications in the sheep, which is an essential step before considering these principles in a clinical setting.
format	article
author	Arvind Manikantan Padma Laura Carrière Frida Krokström Karlsson Edina Sehic Sara Bandstein Tom Tristan Tiemann Mihai Oltean Min Jong Song Mats Brännström Mats Hellström
author_facet	Arvind Manikantan Padma Laura Carrière Frida Krokström Karlsson Edina Sehic Sara Bandstein Tom Tristan Tiemann Mihai Oltean Min Jong Song Mats Brännström Mats Hellström
author_sort	Arvind Manikantan Padma
title	Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning
title_short	Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning
title_full	Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning
title_fullStr	Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning
title_full_unstemmed	Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning
title_sort	towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2d742bd02ed74f76a54a1c4732127536
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Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning

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