Three-dimensional spheroids of dedifferentiated fat cells enhance bone regeneration

Introduction: Mesenchymal stromal/stem cells (MSCs) are multipotent, self-renewing cells that are extensively used in tissue engineering. Dedifferentiated fat (DFAT) cells are derived from adipose tissues and are similar to MSCs. Three-dimensional (3D) spheroid cultures comprising MSCs mimic the bio...

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Autores principales:	Tsukasa Yanagi, Hiroshi Kajiya, Seiichi Fujisaki, Munehisa Maeshiba, Ayako Yanagi-S, Nana Yamamoto-M, Kae Kakura, Hirofumi Kido, Jun Ohno
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Bone regeneration Dedifferentiated fat cells Cell transplantation Calvarial bone defect Medicine (General) R5-920 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/a84c9b827ffd4d569fbbebb0a6416512
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spelling	oai:doaj.org-article:a84c9b827ffd4d569fbbebb0a64165122021-11-14T04:33:30ZThree-dimensional spheroids of dedifferentiated fat cells enhance bone regeneration2352-320410.1016/j.reth.2021.10.004https://doaj.org/article/a84c9b827ffd4d569fbbebb0a64165122021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352320421000821https://doaj.org/toc/2352-3204Introduction: Mesenchymal stromal/stem cells (MSCs) are multipotent, self-renewing cells that are extensively used in tissue engineering. Dedifferentiated fat (DFAT) cells are derived from adipose tissues and are similar to MSCs. Three-dimensional (3D) spheroid cultures comprising MSCs mimic the biological microenvironment more accurately than two-dimensional cultures; however, it remains unclear whether DFAT cells in 3D spheroids possess high osteogenerative ability. Furthermore, it is unclear whether DFAT cells from 3D spheroids transplanted into calvarial bone defects are as effective as those from two-dimensional (2D) monolayers in promoting bone regeneration. Methods: We compared the in vitro osteogenic potential of rat DFAT cells cultured under osteogenic conditions in 3D spheroids with that in 2D monolayers. Furthermore, to elucidate the ability of 3D spheroid DFAT cells to promote bone healing, we examined the in vivo osteogenic potential of transplanting DFAT cells from 3D spheroids or 2D monolayers into a rat calvarial defect model. Results: Osteoblast differentiation stimulated by bone morphogenetic protein-2 (BMP-2) or osteogenesis-inducing medium upregulated osteogenesis-related molecules in 3D spheroid DFAT cells compared with 2D monolayer DFAT cells. BMP-2 activated phosphorylation in the canonical Smad 1/5 pathways in 3D spheroid DFAT cells but phosphorylated ERK1/2 and Smad2 in 2D monolayer DFAT cells. Regardless of osteogenic stimulation, the transplantation of 3D DFAT spheroid cells into rat calvarial defects promoted new bone formation at a greater extent than that of 2D DFAT cells. Conclusions: Compared with 2D DFAT cells, 3D DFAT spheroid cells promote osteoblast differentiation and new bone formation via canonical Smad 1/5 signaling pathways. These results indicate that transplantation of DFAT cells from 3D spheroids, but not 2D monolayers, accelerates bone healing.Tsukasa YanagiHiroshi KajiyaSeiichi FujisakiMunehisa MaeshibaAyako Yanagi-SNana Yamamoto-MKae KakuraHirofumi KidoJun OhnoElsevierarticleBone regenerationDedifferentiated fat cellsCell transplantationCalvarial bone defectMedicine (General)R5-920CytologyQH573-671ENRegenerative Therapy, Vol 18, Iss , Pp 472-479 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bone regeneration Dedifferentiated fat cells Cell transplantation Calvarial bone defect Medicine (General) R5-920 Cytology QH573-671
spellingShingle	Bone regeneration Dedifferentiated fat cells Cell transplantation Calvarial bone defect Medicine (General) R5-920 Cytology QH573-671 Tsukasa Yanagi Hiroshi Kajiya Seiichi Fujisaki Munehisa Maeshiba Ayako Yanagi-S Nana Yamamoto-M Kae Kakura Hirofumi Kido Jun Ohno Three-dimensional spheroids of dedifferentiated fat cells enhance bone regeneration
description	Introduction: Mesenchymal stromal/stem cells (MSCs) are multipotent, self-renewing cells that are extensively used in tissue engineering. Dedifferentiated fat (DFAT) cells are derived from adipose tissues and are similar to MSCs. Three-dimensional (3D) spheroid cultures comprising MSCs mimic the biological microenvironment more accurately than two-dimensional cultures; however, it remains unclear whether DFAT cells in 3D spheroids possess high osteogenerative ability. Furthermore, it is unclear whether DFAT cells from 3D spheroids transplanted into calvarial bone defects are as effective as those from two-dimensional (2D) monolayers in promoting bone regeneration. Methods: We compared the in vitro osteogenic potential of rat DFAT cells cultured under osteogenic conditions in 3D spheroids with that in 2D monolayers. Furthermore, to elucidate the ability of 3D spheroid DFAT cells to promote bone healing, we examined the in vivo osteogenic potential of transplanting DFAT cells from 3D spheroids or 2D monolayers into a rat calvarial defect model. Results: Osteoblast differentiation stimulated by bone morphogenetic protein-2 (BMP-2) or osteogenesis-inducing medium upregulated osteogenesis-related molecules in 3D spheroid DFAT cells compared with 2D monolayer DFAT cells. BMP-2 activated phosphorylation in the canonical Smad 1/5 pathways in 3D spheroid DFAT cells but phosphorylated ERK1/2 and Smad2 in 2D monolayer DFAT cells. Regardless of osteogenic stimulation, the transplantation of 3D DFAT spheroid cells into rat calvarial defects promoted new bone formation at a greater extent than that of 2D DFAT cells. Conclusions: Compared with 2D DFAT cells, 3D DFAT spheroid cells promote osteoblast differentiation and new bone formation via canonical Smad 1/5 signaling pathways. These results indicate that transplantation of DFAT cells from 3D spheroids, but not 2D monolayers, accelerates bone healing.
format	article
author	Tsukasa Yanagi Hiroshi Kajiya Seiichi Fujisaki Munehisa Maeshiba Ayako Yanagi-S Nana Yamamoto-M Kae Kakura Hirofumi Kido Jun Ohno
author_facet	Tsukasa Yanagi Hiroshi Kajiya Seiichi Fujisaki Munehisa Maeshiba Ayako Yanagi-S Nana Yamamoto-M Kae Kakura Hirofumi Kido Jun Ohno
author_sort	Tsukasa Yanagi
title	Three-dimensional spheroids of dedifferentiated fat cells enhance bone regeneration
title_short	Three-dimensional spheroids of dedifferentiated fat cells enhance bone regeneration
title_full	Three-dimensional spheroids of dedifferentiated fat cells enhance bone regeneration
title_fullStr	Three-dimensional spheroids of dedifferentiated fat cells enhance bone regeneration
title_full_unstemmed	Three-dimensional spheroids of dedifferentiated fat cells enhance bone regeneration
title_sort	three-dimensional spheroids of dedifferentiated fat cells enhance bone regeneration
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/a84c9b827ffd4d569fbbebb0a6416512
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Three-dimensional spheroids of dedifferentiated fat cells enhance bone regeneration

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