title: The effect of decellularized matrices on human tendon stem/progenitor cell differentiation and tendon repair.
abstract: It is reported that decellularized collagen matrices derived from dermal skin and bone have been clinically used for tendon repair. However, the varying biological and physical properties of matrices originating from different tissues may influence the differentiation of tendon stem cells, which has not been systematically evaluated. In this study, the effects of collagenous matrices derived from different tissues (tendon, bone and dermis) on the cell differentiation of human tendon stem/progenitor cells (hTSPCs) were investigated, in the context of tendon repair. It was found that all three matrices supported the adhesion and proliferation of hTSPCs despite differences in topography. Interestingly, tendon-derived decellularized matrix promoted the tendinous phenotype in hTSPCs and inhibited their osteogenesis, even under osteogenic induction conditions, through modulation of the teno- and osteolineage-specific transcription factors Scleraxis and Runx2. Bone-derived decellularized matrix robustly induced osteogenic differentiation of hTSPCs, whereas dermal skin-derived collagen matrix had no apparent effect on hTSPC differentiation. Based on the specific biological function of the tendon-derived decellularized matrix, a tissue-engineered tendon comprising TSPCs and tendon-derived matrix was successfully fabricated for Achilles tendon reconstruction. Implantation of this cell-scaffold construct led to a more mature structure (histology score: 4.08 ± 0.61 vs. 8.51 ± 1.66), larger collagen fibrils (52.2 ± 1.6 nm vs. 47.5 ± 2.8 nm) and stronger mechanical properties (stiffness: 21.68 ± 7.1 Nm m(-1) vs.13.2 ± 5.9 Nm m(-1)) of repaired tendons compared to the control group. The results suggest that stem cells promote the rate of repair of Achilles tendon in the presence of a tendinous matrix. This study thus highlights the potential of decellularized matrix for future tissue engineering applications, as well as developing a practical strategy for functional tendon regeneration by utilizing TSPCs combined with tendon-derived decellularized matrix.
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Yin
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Ting
authors.initials: T
authors.lastname: Zhu
authors.forename: Jia-jie
authors.initials: JJ
authors.lastname: Hu
authors.forename: Hai-xin
authors.initials: HX
authors.lastname: Song
authors.forename: Wei-liang
authors.initials: WL
authors.lastname: Shen
authors.forename: Liu-yun
authors.initials: LY
authors.lastname: Jiang
authors.forename: Boon Chin
authors.initials: BC
authors.lastname: Heng
authors.forename: Jun-feng
authors.initials: JF
authors.lastname: Ji
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Ouyang
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D048430:Cell Shape; D002828:Choristoma / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D010012:Osteogenesis / Q000235:genetics; D051381:Rats; D013234:Stem Cells / Q000166:cytology* / Q000648:ultrastructure; D034421:Sus scrofa; D013710:Tendons / Q000166:cytology* / Q000601:surgery / Q000648:ultrastructure; D054457:Tissue Scaffolds / Q000737:chemistry; D014945:Wound Healing
chemical_list: D000469:Alkaline Phosphatase
keywords: Cell-matrix interaction; Decellularized matrix; Tendon regeneration; Tendon stem/progenitor cells; Tissue engineering