title: Scleraxis-overexpressed human embryonic stem cell-derived mesenchymal stem cells for tendon tissue engineering with knitted silk-collagen scaffold.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: 1 Zhejiang Key Laboratory for Tissue Engineering and Repair Technology, School of Medicine, Zhejiang University , Hangzhou, P.R. China .
authors: Xiao
authors: X
authors: Chen
authors: Zi
authors: Z
authors: Yin
authors: Jia-Lin
authors: JL
authors: Chen
authors: Huan-Huan
authors: HH
authors: Liu
authors: Wei-Liang
authors: WL
authors: Shen
authors: Zhi
authors: Z
authors: Fang
authors: Ting
authors: T
authors: Zhu
authors: Junfeng
authors: J
authors: Ji
authors: Hong-Wei
authors: HW
authors: Ouyang
authors: Xiao-Hui
authors: XH
authors: Zou
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001696:Biomechanical Phenomena / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D020007:Implants, Experimental; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008648:Mesoderm / Q000166:cytology; D008819:Mice, Nude; D009928:Organ Specificity; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects; D047011:Silk / Q000494:pharmacology*; D013710:Tendons / Q000187:drug effects / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D003094:Collagen; D047011:Silk; C093504:SCX protein, human