title: The regulation of tendon stem cell differentiation by the alignment of nanofibers.
abstract: Tendon is a specific connective tissue composed of parallel collagen fibers. The effect of this tissue-specific matrix orientation on stem cell differentiation has not been investigated. This study aimed to determine the effects of nanotopography on the differentiation of human tendon stem/progenitor cells (hTSPCs) and develop a biomimetic scaffold for tendon tissue engineering. The immuno-phenotype of fetal hTSPCs was identified by flow cytometry. The multipotency of hTSPCs toward osteogenesis, adipogenesis, and chondrogenesis was confirmed. Then, the hTSPCs were seeded onto aligned or randomly-oriented poly (l-lactic acid) nanofibers. Scanning electron micrographs showed that hTSPCs were spindle-shaped and well orientated on the aligned nanofibers. The expression of tendon-specific genes was significantly higher in hTSPCs growing on aligned nanofibers than those on randomly-oriented nanofibers in both normal and osteogenic media. In addition, alkaline phosphatase activity and alizarin red staining showed that the randomly-oriented fibrous scaffold induced osteogenesis, while the aligned scaffold hindered the process. Moreover, aligned cells expressed significantly higher levels of integrin alpha1, alpha5 and beta1 subunits, and myosin II B. In in vivo experiments, the aligned nanofibers induced the formation of spindle-shaped cells and tendon-like tissue. In conclusion, the aligned electrospun nanofiber structure provides an instructive microenvironment for hTSPC differentiation and may lead to the development of desirable engineered tendons.
authors.affiliation: Center for Stem Cell and Tissue Engineering, Department of Sports Medicine, School of Medicine, Zhejiang University, and Department of Orthopedic Surgery, 2nd Affiliated Hospital, Hangzhou, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Yin
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Jia Lin
authors.initials: JL
authors.lastname: Chen
authors.forename: Wei Liang
authors.initials: WL
authors.lastname: Shen
authors.forename: Thi Minh
authors.initials: TM
authors.lastname: Hieu Nguyen
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Ouyang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism; D008422:Materials Testing; D051379:Mice; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology; D057139:Nanofibers / Q000737:chemistry*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D013314:Stress, Mechanical; D013710:Tendons / Q000166:cytology* / Q000502:physiology; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D015703:Antigens, CD; D001672:Biocompatible Materials; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide)