Stem Cells：利用人体胚胎干细胞培育出关节软骨

生物谷

    生物谷报道：位于美国休斯顿的莱斯大学生物医学工程师发明了一种新技术，可以用人体胚胎干细胞培育软骨组织。这种方法可以为膝盖、上下颌、臀部和其他关节的外科手术修补提供软骨组织替换品。

    由于人体自身的软骨组织不能自我愈合，研究人员早就开始在实验室里想方设法培育可以替换的软骨组织，以便用于人体受伤后的外科修补手术。莱斯大学的生物工程学教授爱斯内修说：“该研究提供了一种新颖的可以从胚胎干细胞培育出类似软骨组织细胞的方法，使人类可以借助生物工程学原理，利用人体胚胎干细胞培育出软骨组织，这在人类历史上还是第一次。”

    科学家们利用了一系列的刺激物，发明了一种可以将干细胞转化为软骨组织细胞的方法。在此基础上，研究者又进一步发展了可以将软骨细胞转化为软骨组织的程序。研究结果显示，这些软骨组织可以模仿生成人体内不同类型的软骨组织，如透明的关节软骨。这种软骨在所有的关节和膝盖的弯液面及上下颌的关节———纤维软骨处都可发现。爱斯内修说：“结果是令人兴奋的。采用相似的方法，我们可以将从软骨组织得到的干细胞转化为更加强健的软骨，以用于临床治疗。”

    干细胞是指那些同时具有自我更新和产生分化细胞能力的细胞。尤其在早期胚胎发育过程中，它们可以产生构成各种身体器官的组织。这种细胞就是胚胎干细胞，发育生物学家将它们称为“全能性细胞”。在所有的人群当中，有多种类型的“成人”干细胞在体内工作。成人干细胞能够替代血液、骨头、皮肤和人体内的其他组织。但成人干细胞只能转变为有限的几种类型的细胞，而胚胎干细胞从理论上来说，可以转变成人体内任何一种类型的细胞。爱斯内修的研究小组成为世界上研究软骨组织细胞，特别是人体工程学软骨组织的成功者之一。他说，胚胎干细胞优于成人干细胞的最主要优点在于它的可塑性和延展性。

    从2005年开始，爱斯内修小组开始研究胚胎干细胞。他们的研究结果刊登于9月份出版的《干细胞》期刊上。该研究由莱斯大学资助，采用的干细胞来自美国国立卫生研究院批准认可的干细胞系。（科技日报）

原始出处:

First published online May 31, 2007
Stem Cells Vol. 25 No. 9 September 2007, pp. 2183 -2190
doi:10.1634/stemcells.2007-0105; www.StemCells.com

EMBRYONIC STEM CELLS

Tissue Engineering with Chondrogenically Differentiated Human Embryonic Stem Cells

Eugene J. Koaya,b, Gwen M. B. Hobena,b, Kyriacos A. Athanasioua

aDepartment of Bioengineering, Rice University, Houston, Texas, USA;
bBaylor College of Medicine, Houston, Texas, USA

Key Words. Human embryonic stem cells • Chondrogenesis • Cartilage • Tissue engineering

Correspondence: Kyriacos Athanasiou, Ph.D., P.E., Rice University, Department of Bioengineering, MS-142, P.O. Box 1892, Houston, Texas 77251-1892, USA. Telephone: (713) 348-6385; Fax: (713) 348-5877; e-mail: athanasiou@rice.edu

Received February 7, 2007; accepted for publication May 17, 2007.
First published online in STEM CELLS EXPRESS May 31, 2007.

This study describes the development and application of a novel strategy to tissue engineer musculoskeletal cartilages with human embryonic stem cells (hESCs). This work expands the presently limited understanding of how to chondrogenically differentiate hESCs through the use of chondrogenic medium alone (CM) or CM with two growth factor regimens: transforming growth factor (TGF)-ß3 followed by TGF-ß1 plus insulin-like growth factor (IGF)-I or TGF-ß3 followed by bone morphogenic protein (BMP)-2. It also extends the use of the resulting chondrogenically differentiated cells for cartilage tissue engineering through a scaffoldless approach called self-assembly, which was conducted in two modes: with (a) embryoid bodies (EBs) or (b) a suspension of cells enzymatically dissociated from the EBs. Cells from two of the differentiation conditions (CM alone and TGF-ß3 followed by BMP-2) produced fibrocartilage-like constructs with high collagen I content, low collagen II content, relatively high total collagen content (up to 24% by dry weight), low sulfated glycosaminoglycan content ( $~$ 4% by dry weight), and tensile properties on the order of megapascals. In contrast, hESCs treated with TGF-ß3 followed by TGF-ß1 + IGF-I produced constructs with no collagen I. Results demonstrated significant differences among the differentiation conditions in terms of other biochemical and biomechanical properties of the self-assembled constructs, suggesting that distinct growth factor regimens differentially modulate the potential of the cells to produce cartilage. Furthermore, this work shows that self-assembly of cells obtained by enzymatic dissociation of EBs is superior to self-assembly of EBs. Overall, the results of this study raise the possibility of manipulating the characteristics of hESC-generated tissue toward specific musculoskeletal cartilage applications.