A single-cell transcriptome of mesenchymal stromal cells to fabricate bioactive hydroxyapatite materials for bone regeneration.
A single-cell transcriptome of mesenchymal stromal cells to fabricate bioactive hydroxyapatite materials for bone regeneration.
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DOI：
10.1016/j.bioactmat.2021.08.009
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发表时间：
2022-03
影响因子：
18.9
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Guo P;Liu X;Zhang P;He Z;Li Z;Alini M;Richards RG;Grad S;Stoddart MJ;Zhou G;Zou X;Chan D;Tian W;Chen D;Gao M;Zhou Z;Liu S
骨修复材料的成骨微环境在促进骨再生中起着关键作用，但目前对成骨微环境的认识还不完全，这极大地限制了这类生物活性材料的应用。在这里，不同的成骨微环境，包括三维（3D）羟基磷灰石（HA）支架和成骨培养基（OM），在体外间充质基质细胞（MSC）的转录景观绘制在单细胞分辨率。我们的研究结果表明，通过连续激活成骨相关信号通路，沿着炎症和血管生成，但抑制脂肪生成和纤维化，在HA支架中发生了一个类似于软骨内骨化的成骨过程。此外，我们揭示了OM介导的成骨过程中的机制涉及ZBTB16和WNT信号通路。还证实了MSC的异质性。体外成骨实验显示LRRC75A+ MSCs对WNT相关的成骨过程有较好的利用，PCDH10+ MSCs对羟磷灰石相关的成骨过程有优势。这些发现提供了进一步的理解OM条件和HA支架调节的细胞活性，为成骨生物材料的改进提供了新的见解。该图谱为MSC异质性和HA支架成骨微环境的研究提供了蓝图，并为生物活性材料在骨再生中的应用提供了数据库参考。干细胞的单细胞转录组被绘制用于骨再生。PCDH10+细胞加速羟基磷灰石相关的骨生成。成骨培养基对羟基磷灰石相关的成骨有不良影响。羟基磷灰石体外细胞修饰的时间窗口是关键。生物材料的缺氧和炎症微环境值得关注。
The osteogenic microenvironment of bone-repairing materials plays a key role in accelerating bone regeneration but remains incompletely defined, which significantly limits the application of such bioactive materials. Here, the transcriptional landscapes of different osteogenic microenvironments, including three-dimensional (3D) hydroxyapatite (HA) scaffolds and osteogenic medium (OM), for mesenchymal stromal cells (MSCs) in vitro were mapped at single-cell resolution. Our findings suggested that an osteogenic process reminiscent of endochondral ossification occurred in HA scaffolds through sequential activation of osteogenic-related signaling pathways, along with inflammation and angiogenesis, but inhibition of adipogenesis and fibrosis. Moreover, we revealed the mechanism during OM-mediated osteogenesis involves the ZBTB16 and WNT signaling pathways. Heterogeneity of MSCs was also demonstrated. In vitro ossification of LRRC75A+ MSCs was shown to have better utilization of WNT-related ossification process, and PCDH10+ MSCs with superiority in hydroxyapatite-related osteogenic process. These findings provided further understanding of the cellular activity modulated by OM conditions and HA scaffolds, providing new insights for the improvement of osteogenic biomaterials. This atlas provides a blueprint for research on MSC heterogeneity and the osteogenic microenvironment of HA scaffolds and a database reference for the application of bioactive materials for bone regeneration. A single-cell transcriptome of stem cells is mapped for bone regeneration. PCDH10+ cells accelerate hydroxyapatite-related osteogenesis. Osteogenic medium shows adverse effects on hydroxyapatite-related osteogenesis. A time window for cell modification of hydroxyapatite in vitro is critical. The hypoxic and inflammatory microenvironment of biomaterials deserves attention.
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影响因子：
14
作者：
Ho-Shui-Ling A;Bolander J;Rustom LE;Johnson AW;Luyten FP;Picart C
通讯作者：
Picart C
影响因子：
64.5
作者：
Baryawno, Ninib;Przybylski, Dariusz;Scadden, David T.
通讯作者：
Scadden, David T.
影响因子：
16.1
作者：
Agarwal R;García AJ
通讯作者：
García AJ
DOI：
10.1016/j.bbrc.2008.06.121
发表时间：
2008-09-12
影响因子：
3.1
作者：
Chiellini, Chiara;Grenningloh, Gabriele;Amri, Ez-Zoubir
通讯作者：
Amri, Ez-Zoubir
影响因子：
1.2
作者：
Alimperti, Stella;Andreadis, Stelios T.
通讯作者：
Andreadis, Stelios T.