Muscle tissue engineering and regeneration through epigenetic reprogramming and scaffold manipulation

Tan, ShihJye; Fang, Josephine Y.; Wu, Yaling; Yang, Zhi; Liang, Gangning; Han, Bo

doi:10.1038/srep16333

Cited by 24 publications

(22 citation statements)

References 62 publications

(83 reference statements)

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“…Thanks to its powerful effects, this compound may be used to increase chromatin plasticity and facilitate phenotype changes1213. Several studies reported 5-aza-CR ability to facilitate adult somatic cell switch from one phenotype to a different one141516. In particular, we demonstrated that a short exposure to 5-aza-CR allows a transient passage through a plastic chromatin state.…”

mentioning

confidence: 61%

5-azacytidine affects TET2 and histone transcription and reshapes morphology of human skin fibroblasts

Manzoni

Pennarossa

deEguileor

et al. 2016

Sci Rep

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Phenotype definition is controlled by epigenetic regulations that allow cells to acquire their differentiated state. The process is reversible and attractive for therapeutic intervention and for the reactivation of hypermethylated pluripotency genes that facilitate transition to a higher plasticity state. We report the results obtained in human fibroblasts exposed to the epigenetic modifier 5-azacytidine (5-aza-CR), which increases adult cell plasticity and facilitates phenotype change. Although many aspects controlling its demethylating action have been widely investigated, the mechanisms underlying 5-aza-CR effects on cell plasticity are still poorly understood. Our experiments confirm decreased global methylation, but also demonstrate an increase of both Formylcytosine (5fC) and 5-Carboxylcytosine (5caC), indicating 5-aza-CR ability to activate a direct and active demethylating effect, possibly mediated via TET2 protein increased transcription. This was accompanied by transient upregulation of pluripotency markers and incremented histone expression, paralleled by changes in histone acetylating enzymes. Furthermore, adult fibroblasts reshaped into undifferentiated progenitor-like phenotype, with a sparse and open chromatin structure. Our findings indicate that 5-aza-CR induced somatic cell transition to a higher plasticity state is activated by multiple regulations that accompany the demethylating effect exerted by the modifier.

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mentioning

confidence: 61%

5-azacytidine affects TET2 and histone transcription and reshapes morphology of human skin fibroblasts

Manzoni

Pennarossa

deEguileor

et al. 2016

Sci Rep

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“…Compared to other types of mesenchymal stem cells, ADSCs possess the highest proliferation potential and exhibit high tolerance to serum deprivation-induced apoptosis 41 . Moreover, ADSCs can be successfully induced to differentiate into myoblasts by 5-azacytidine and have been reported to treat muscle disorders by our group and others 19 , 42 , 43 . In our experiments, we took autologous ADSCs as seed cells, promoted their muscle differentiation with 10 μM 5-azacytidine and 5% horse serum, and built the muscular layer of bionic urethras.…”

Section: Discussionmentioning

confidence: 94%

Fabrication of Tissue-Engineered Bionic Urethra Using Cell Sheet Technology and Labeling By Ultrasmall Superparamagnetic Iron Oxide for Full-Thickness Urethral Reconstruction

Zhou¹,

Yang²,

Zou³

et al. 2017

Theranostics

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Urethral strictures remain a reconstructive challenge, due to less than satisfactory outcomes and high incidence of stricture recurrence. An “ideal” urethral reconstruction should establish similar architecture and function as the original urethral wall. We fabricated a novel tissue-engineered bionic urethras using cell sheet technology and report their viability in a canine model. Small amounts of oral and adipose tissues were harvested, and adipose-derived stem cells, oral mucosal epithelial cells, and oral mucosal fibroblasts were isolated and used to prepare cell sheets. The cell sheets were hierarchically tubularized to form 3-layer tissue-engineered urethras and labeled by ultrasmall super-paramagnetic iron oxide (USPIO). The constructed tissue-engineered urethras were transplanted subcutaneously for 3 weeks to promote the revascularization and biomechanical strength of the implant. Then, 2 cm length of the tubularized penile urethra was replaced by tissue-engineered bionic urethra. At 3 months of urethral replacement, USPIO-labeled tissue-engineered bionic urethra can be effectively detected by MRI at the transplant site. Histologically, the retrieved bionic urethras still displayed 3 layers, including an epithelial layer, a fibrous layer, and a myoblast layer. Three weeks after subcutaneous transplantation, immunofluorescence analysis showed the density of blood vessels in bionic urethra was significantly increased following the initial establishment of the constructs and was further up-regulated at 3 months after urethral replacement and was close to normal level in urethral tissue. Our study is the first to experimentally demonstrate 3-layer tissue-engineered urethras can be established using cell sheet technology and can promote the regeneration of structural and functional urethras similar to normal urethra.

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“…Myogenin has been extensively reported to be a late marker of myoblast fusion, required for terminal differentiation ( Tan et al, 2015 ). Mudera et al (2010) and Smith et al (2012) demonstrated the expression pattern of MYOG in similar tissue engineered models, where comparisons were made against 2D controls.…”

Section: Discussionmentioning

confidence: 99%

An Assessment of Myotube Morphology, Matrix Deformation, and Myogenic mRNA Expression in Custom-Built and Commercially Available Engineered Muscle Chamber Configurations

et al. 2018

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There are several three-dimensional (3D) skeletal muscle (SkM) tissue engineered models reported in the literature. 3D SkM tissue engineering (TE) aims to recapitulate the structure and function of native (in vivo) tissue, within an in vitro environment. This requires the differentiation of myoblasts into aligned multinucleated myotubes surrounded by a biologically representative extracellular matrix (ECM). In the present work, a new commercially available 3D SkM TE culture chamber manufactured from polyether ether ketone (PEEK) that facilitates suitable development of these myotubes is presented. To assess the outcomes of the myotubes within these constructs, morphological, gene expression, and ECM remodeling parameters were compared against a previously published custom-built model. No significant differences were observed in the morphological and gene expression measures between the newly introduced and the established construct configuration, suggesting biological reproducibility irrespective of manufacturing process. However, TE SkM fabricated using the commercially available PEEK chambers displayed reduced variability in both construct attachment and matrix deformation, likely due to increased reproducibility within the manufacturing process. The mechanical differences between systems may also have contributed to such differences, however, investigation of these variables was beyond the scope of the investigation. Though more expensive than the custom-built models, these PEEK chambers are also suitable for multiple use after autoclaving. As such this would support its use over the previously published handmade culture chamber system, particularly when seeking to develop higher-throughput systems or when experimental cost is not a factor.

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Muscle tissue engineering and regeneration through epigenetic reprogramming and scaffold manipulation

Cited by 24 publications

References 62 publications

5-azacytidine affects TET2 and histone transcription and reshapes morphology of human skin fibroblasts

5-azacytidine affects TET2 and histone transcription and reshapes morphology of human skin fibroblasts

Fabrication of Tissue-Engineered Bionic Urethra Using Cell Sheet Technology and Labeling By Ultrasmall Superparamagnetic Iron Oxide for Full-Thickness Urethral Reconstruction

An Assessment of Myotube Morphology, Matrix Deformation, and Myogenic mRNA Expression in Custom-Built and Commercially Available Engineered Muscle Chamber Configurations

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