In vivo commitment and functional tissue regeneration using human embryonic stem cell-derived mesenchymal cells

In vivo commitment and functional tissue regeneration using human embryonic stem cell-derived mesenchymal cells
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DOI:
10.1073/pnas.0809680106
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发表时间:
2008-12-30
影响因子:
11.1
通讯作者:
Elisseeff, Jennifer
Elisseeff, Jennifer
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hwang, Nathaniel S.;Varghese, Shyni;Elisseeff, Jennifer

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利用人类胚胎干细胞(HESCs)开发具有临床意义的再生医学疗法需要生产一种简单且容易扩展的细胞群,该细胞群可以被定向在体内环境中形成具有功能的3D组织。我们描述了一种从人胚胎干细胞(HESCs)中高效地分离和鉴定间充质干细胞(hESCd-MSCs)的方法,该细胞具有多向分化潜能,并能够在体外产生脂肪、软骨和骨。此外,我们强调了它们在体内的存活和在包含软骨细胞分泌的形态发生因子和水凝胶的微环境中对软骨形成谱系的承诺。在大鼠的骨软骨缺损处,经软骨细胞定向的hESCD-MSCs治疗后,建立了正常的软骨结构。鉴于可用于组织工程应用的细胞来源有限,这些胚胎来源的细胞在肌肉骨骼组织再生应用中显示出巨大的潜力。
Development of clinically relevant regenerative medicine therapies using human embryonic stem cells (hESCs) requires production of a simple and readily expandable cell population that can be directed to form functional 3D tissue in an in vivo environment. We describe an efficient derivation method and characterization of mesenchymal stem cells (MSCs) from hESCs (hESCd-MSCs) that have multilineage differentiation potential and are capable of producing fat, cartilage, and bone in vitro. Furthermore, we highlight their in vivo survival and commitment to the chondrogenic lineage in a microenvironment comprising chondrocyte-secreted morphogenetic factors and hydrogels. Normal cartilage architecture was established in rat osteochondral defects after treatment with chondrogenically-committed hESCd-MSCs. In view of the limited available cell sources for tissue engineering applications, these embryonic-derived cells show significant potential in musculoskeletal tissue regeneration applications.