title: Muscle tissue engineering and regeneration through epigenetic reprogramming and scaffold manipulation.
abstract: Efficiency of cell-based tissue engineering and regenerative medicine has been limited by inadequate cellular responses to injury because of aging and poor controllability of cellular interactions. Since cell progression is under a tight epigenetic regulation, epigenetic modulators such as 5-azacytidine (5-Aza-CR) have been utilized to facilitate reprogramming and development of somatic cells in 2-dimensional (2-D) settings. Nonetheless, progression of a specific tissue lineage toward the terminal phenotype is dependent not only on the genomic potential, but also on the microenvironment cues that are beyond the capability of 2-D approaches. In this study, we investigated the combined effects of matrices of variable rigidities and the treatment with the epigenetic modulator 5-Aza-CR on reprogramming adipose-derived stromal cells (ADSCs) into myoblast-like cells by utilizing tunable transglutaminase cross-linked gelatin (Col-Tgel) in vitro and in vivo. Our experiments demonstrated that cellular plasticity and trans-differentiation were significantly enhanced when ADSCs were treated with an effective dose of 5-Aza-CR (1.25 to 12.5 ng) in the optimal myogenic matrix (15 ± 5 kPa Col-Tgel). Our findings suggest that both physical signals and chemical milieu are critical for the regulation of cellular responses.
authors.affiliation: Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Tan
authors.affiliation: Nimni-Cordoba Tissue Engineering and Drug Discovery Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, Keck Medical School, University of Southern California, Los Angeles, CA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Fang
authors.affiliation: Nimni-Cordoba Tissue Engineering and Drug Discovery Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, Keck Medical School, University of Southern California, Los Angeles, CA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Nimni-Cordoba Tissue Engineering and Drug Discovery Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, Keck Medical School, University of Southern California, Los Angeles, CA.
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, CA.
authors.forename: G
authors.initials: G
authors.lastname: Liang
authors.affiliation: Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA.|Nimni-Cordoba Tissue Engineering and Drug Discovery Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, Keck Medical School, University of Southern California, Los Angeles, CA.
authors.forename: B
authors.initials: B
authors.lastname: Han
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics*; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D009132:Muscles; D010641:Phenotype; D051381:Rats; D012038:Regeneration; D044968:Regenerative Medicine; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D015533:Transcriptional Activation
chemical_list: D001374:Azacitidine