Engineering bone tissue from human embryonic stem cells

Engineering bone tissue from human embryonic stem cells
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DOI:
10.1073/pnas.1201830109
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发表时间:
2012-05-29
影响因子:
11.1
通讯作者:
Vunjak-Novakovic, Gordana
Vunjak-Novakovic, Gordana
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Marolt, Darja;Campos, Ivan Marcos;Vunjak-Novakovic, Gordana

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在广泛的骨缺损中,组织损伤和缺氧导致细胞死亡,导致缓慢和不完全的愈合。人类胚胎干细胞(HESC)可以在健康的骨骼中产生所有的特化血统,因此特别适合于帮助受损骨骼的再生。我们发现,在中等灌流的生物反应器中,在3D骨传导支架上培养hESC来源的间充质前体细胞可以形成大而致密的骨结构。值得注意的是,在免疫缺陷小鼠体内植入工程化骨8wk后,骨基质得以维持和成熟,没有形成畸胎瘤,而未分化的hESCs单独或植入到骨支架中时,这种情况一直存在。我们的研究提供了一个原则证据,即组织工程学方案可以成功地应用于hESC前体细胞,以培养用于基础研究和翻译研究的骨移植。
In extensive bone defects, tissue damage and hypoxia lead to cell death, resulting in slow and incomplete healing. Human embryonic stem cells (hESC) can give rise to all specialized lineages found in healthy bone and are therefore uniquely suited to aid regeneration of damaged bone. We show that the cultivation of hESC-derived mesenchymal progenitors on 3D osteoconductive scaffolds in bioreactors with medium perfusion leads to the formation of large and compact bone constructs. Notably, the implantation of engineered bone in immunodeficient mice for 8 wk resulted in the maintenance and maturation of bone matrix, without the formation of teratomas that is consistently observed when undifferentiated hESCs are implanted, alone or in bone scaffolds. Our study provides a proof of principle that tissue-engineering protocols can be successfully applied to hESC progenitors to grow bone grafts for use in basic and translational studies.