title: Microgrooved topographical surface directs tenogenic lineage specific differentiation of mouse tendon derived stem cells.
abstract: Tendon derived stem cells (TDSCs) are the endogenous cell source for tenocyte turnover and tendon functional maintenance. They are also the important cell source for tendon engineering and regeneration. In addition, TDSCs also play an important role in tendinopathy via their non-tenogenic lineage differentiation. It has been well demonstrated that cell shape could determine mesenchymal stem cell (MSC) lineage differentiation. In this study, a parallel microgrooved polydimethylsiloxane (PDMS) membrane (10 µm groove width and 3 µm depth) was employed to investigate the role of cell elongation via this particular topographic surface in directing murine TDSC (mTDSC) lineage differentiation. The results showed that elongated mTDSCs exhibited significantly enhanced the gene expression of tenogenic markers when compared to the spread cells that grew on smooth PDMS membrane including tenomodulin, scleraxis, collagens I, III, and VI, decorin and tenascin (p  <  0.05). Meanwhile, stemness related genes such as Nanog, Sox2 and Oct4 were significantly inhibited for their expression in elongated mTDSCs (p  <  0.05). When under tri-lineage induced differentiation, cell elongation significantly inhibited mTDSC differentiation towards chondrogenic and adipogenic lineages (p  <  0.05). Furthermore, cell elongation could significantly inhibit mTDSC osteogenic lineage differentiation (p  <  0.05) induced by BMP-2, a tendinopathy mimicking stimulant. In conclusion, simulation of native tendon structure via using parallel microgrooved topography can promote mTDSC differentiation specifically towards tenogenic lineage and prevent non-tenogenic lineage differentiation, providing an insight into the design of tendon regenerative materials.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. Authors who contributed equally.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shi
authors.forename: Kaili
authors.initials: K
authors.lastname: Zhou
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Guangdong
authors.initials: G
authors.lastname: Zhou
authors.forename: Yilin
authors.initials: Y
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D048430:Cell Shape; D005434:Flow Cytometry; D015870:Gene Expression; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000187:drug effects; D013710:Tendons / Q000166:cytology*; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2