期刊
TISSUE ENGINEERING PART A
卷 20, 期 11-12, 页码 1583-1592出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ten.tea.2012.0656
关键词
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资金
- NSFC [81330041, 81125014, 31271041, 81201396, J1103603]
- Fundamental Research Funds for the Central Universities, International Science & Technology Cooperation Program of China [2011DFA32190]
- National Key Scientific Program [2012CB966604]
- 863 Program [2012AA020503]
- Regenerative Medicine in Innovative Medical Subjects of Zhejiang Province
- Medical and health science and technology plan of Department of Health of Zhejiang Province [2013RCA010]
Aim: Despite our previous study that demonstrates that human embryonic stem cells (hESCs) can be used as seed cells for tendon tissue engineering after stepwise induction, suboptimal tendon regeneration implies that a new strategy needs to be developed for tendon repair. We investigated whether overexpression of the tendon-specific transcription factor scleraxis (SCX) in hESC-derived mesenchymal stem cells (hESC-MSCs) together with knitted silk-collagen sponge scaffold could promote tendon regeneration. Methods and Results: hESCs were initially differentiated into MSCs and then engineered with scleraxis (SCX+hESC-MSCs). Engineered tendons were constructed with SCX+hESC-MSCs and a knitted silk-collagen sponge scaffold and then mechanical stress was applied. SCX elevated tendon gene expression in hESC-MSCs and concomitantly attenuated their adipogenic and chondrogenic potential. Mechanical stress further augmented the expression of tendon-specific genes in SCX+hESC-MSC-engineered tendon. Moreover, in vivo mechanical stimulation promoted the alignment of cells and increased the diameter of collagen fibers after ectopic transplantation. In the in vivo tendon repair model, the SCX+hESC-MSC-engineered tendon enhanced the regeneration process as shown by histological scores and superior mechanical performance compared with control cells, especially at early stages. Conclusion: Our study offers new evidence concerning the roles of SCX in tendon differentiation and regeneration. We demonstrated a novel strategy of combining hESCs, genetic engineering, and tissue-engineering principles for tendon regeneration, which are important for the future application of hESCs and silk scaffolds for tendon repair.
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