title: Repair of full-thickness tendon injury using connective tissue progenitors efficiently derived from human embryonic stem cells and fetal tissues.
abstract: The use of stem cells for tissue engineering (TE) encourages scientists to design new platforms in the field of regenerative and reconstructive medicine. Human embryonic stem cells (hESC) have been proposed to be an important cell source for cell-based TE applications as well as an exciting tool for investigating the fundamentals of human development. Here, we describe the efficient derivation of connective tissue progenitors (CTPs) from hESC lines and fetal tissues. The CTPs were significantly expanded and induced to generate tendon tissues in vitro, with ultrastructural characteristics and biomechanical properties typical of mature tendons. We describe a simple method for engineering tendon grafts that can successfully repair injured Achilles tendons and restore the ankle joint extension movement in mice. We also show the CTP's ability to differentiate into bone, cartilage, and fat both in vitro and in vivo. This study offers evidence for the possibility of using stem cell-derived engineered grafts to replace missing tissues, and sets a basic platform for future cell-based TE applications in the fields of orthopedics and reconstructive surgery.
authors.affiliation: Sohnis and Forman Families Center for Stem Cell and Tissue Regeneration Research, Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Shahar
authors.initials: S
authors.lastname: Cohen
authors.forename: Lucy
authors.initials: L
authors.lastname: Leshansky
authors.forename: Eyal
authors.initials: E
authors.lastname: Zussman
authors.forename: Michael
authors.initials: M
authors.lastname: Burman
authors.forename: Samer
authors.initials: S
authors.lastname: Srouji
authors.forename: Erella
authors.initials: E
authors.lastname: Livne
authors.forename: Natalie
authors.initials: N
authors.lastname: Abramov
authors.forename: Joseph
authors.initials: J
authors.lastname: Itskovitz-Eldor
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003239:Connective Tissue Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D005333:Fetus / Q000166:cytology* / Q000648:ultrastructure; D006801:Humans; D007621:Karyotyping; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000648:ultrastructure; D013708:Tendon Injuries / Q000378:metabolism / Q000628:therapy*; D023822:Tissue Engineering / Q000379:methods*