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胎儿骨髓来源间充质干细胞/基质细胞增强 BMP7 负载支架的人源化和骨形成。

Fetal Bone Marrow-Derived Mesenchymal Stem/Stromal Cells Enhance Humanization and Bone Formation of BMP7 Loaded Scaffolds.

机构信息

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.

The University of Queensland, UQ Centre for Clinical Research, Brisbane, Queensland, Australia.

出版信息

Biotechnol J. 2017 Dec;12(12). doi: 10.1002/biot.201700414. Epub 2017 Sep 25.

Abstract

Tissue engineered constructs built with human cells capable of generating a bone-like organ within the mouse have attracted considerable interest over the past decade. Here, we aimed to compare the utility of human mesenchymal stem/stromal cells (MSC) isolated from fetal term placenta (fPL-MSC) and fetal first trimester bone marrow (fBM-MSC) in a polycaprolactone scaffold/BMP7-based model in nude mice. Furthermore, fPL-MSC were co-seeded with fetal placenta-derived endothelial colony forming cells (ECFC) to assess the impact of ECFC on fPL-MSC osteogenesis. X-ray radiography and micro computed tomography analyses showed enhanced bone formation in all BMP7 groups; however there was no difference after 2 months in bone formation between scaffolds seeded with fPL-MSC alone or combination of ECFC and fPL-MSC. Of interest, fBM-MSC showed the highest level of bone formation. Additionally, endochondral ossification contributed in generation of bone in fBM-MSC. Histological analysis showed the primary role of BMP in generation of cortical and trabecular bone, and the recruitment of hematopoietic cells to the scaffolds. Current in vivo engineered bone organs can potentially be used for drug screening or as models to study bone tissue development in combination with haematopoiesis.

摘要

在过去的十年中,使用能够在小鼠体内生成类骨器官的人类细胞构建组织工程化构建体引起了相当大的兴趣。在这里,我们旨在比较从胎盘中分离的人骨髓间充质干细胞(fPL-MSC)和胎儿第一孕期骨髓(fBM-MSC)在聚己内酯支架/BMP7 模型中的效用在裸鼠中。此外,fPL-MSC 与胎盘中的内皮祖细胞(ECFC)共接种,以评估 ECFC 对 fPL-MSC 成骨的影响。X 射线射线照相和微计算机断层扫描分析显示所有 BMP7 组均增强了骨形成;然而,在 2 个月后,单独接种 fPL-MSC 或 ECFC 和 fPL-MSC 组合的支架之间的骨形成没有差异。有趣的是,fBM-MSC 显示出最高水平的骨形成。此外,骺软骨内骨化有助于 fBM-MSC 生成骨。组织学分析表明 BMP 在皮质骨和小梁骨生成以及造血细胞募集到支架中的主要作用。目前的体内工程化骨器官可潜在地用于药物筛选或作为模型,与造血相结合来研究骨组织发育。

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