Three-dimensional spheroids of dedifferentiated fat cells enhance bone regeneration.
Three-dimensional spheroids of dedifferentiated fat cells enhance bone regeneration.
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DOI：
10.1016/j.reth.2021.10.004
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发表时间：
2021-12
影响因子：
4.3
通讯作者：
Ohno J
中科院分区：
文献类型：
--
作者：
Yanagi T;Kajiya H;Fujisaki S;Maeshiba M;Yanagi-S A;Yamamoto-M N;Kakura K;Kido H;Ohno J
间充质基质/干细胞（MSC）是多能、自我更新的细胞，广泛用于组织工程。去分化脂肪（DFAT）细胞源自脂肪组织，与间充质干细胞相似。包含 MSC 的三维 (3D) 球状培养物比二维培养物更准确地模拟生物微环境；然而，3D球体中的DFAT细胞是否具有高成骨能力仍不清楚。此外，尚不清楚移植到颅骨骨缺损中的 3D 球体 DFAT 细胞在促进骨再生方面是否与二维 (2D) 单层细胞的 DFAT 细胞一样有效。我们比较了在 3D 球体和 2D 单层成骨条件下培养的大鼠 DFAT 细胞的体外成骨潜力。此外，为了阐明 3D 球体 DFAT 细胞促进骨愈合的能力，我们检查了将 3D 球体或 2D 单层 DFAT 细胞移植到大鼠颅骨缺损模型中的体内成骨潜力。与 2D 单层 DFAT 细胞相比，骨形态发生蛋白 2 (BMP-2) 或成骨诱导培养基刺激的成骨细胞分化上调 3D 球状 DFAT 细胞中的成骨相关分子。 BMP-2 激活 3D 球状 DFAT 细胞中经典 Smad 1/5 通路的磷酸化，但磷酸化 2D 单层 DFAT 细胞中的 ERK1/2 和 Smad2。无论成骨刺激如何，将3D DFAT球状细胞移植到大鼠颅骨缺损中比2D DFAT细胞更能促进新骨形成。与 2D DFAT 细胞相比，3D DFAT 球状细胞通过典型的 Smad 1/5 信号通路促进成骨细胞分化和新骨形成。这些结果表明，移植 3D 球体（而非 2D 单层细胞）的 DFAT 细胞可加速骨愈合。
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. 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. 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. 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.
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影响因子：
5.2
作者：
Bartosh, Thomas J.;Yloestalo, Joni H.;Bazhanov, Nikolay;Kuhlman, Jessica;Prockop, Darwin J.
通讯作者：
Prockop, Darwin J.
影响因子：
4
作者：
Guo, Ling;Ge, Jianfeng;Wu, Yaojiong
通讯作者：
Wu, Yaojiong
影响因子：
7.5
作者：
Ader, Marius;Tanaka, Elly M.
通讯作者：
Tanaka, Elly M.
影响因子：
4.3
作者：
Sugawara, Atsunori;Sato, Soh
通讯作者：
Sato, Soh
影响因子：
5.6
作者：
Li Y;Ge C;Franceschi RT
通讯作者：
Franceschi RT