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Engineering an in vitro environment to study regeneration
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.580.1
Subject(s) - blastema , myogenesis , extracellular matrix , microbiology and biotechnology , regeneration (biology) , fibronectin , multinucleate , skeletal muscle , chemistry , stem cell , matrigel , anatomy , fragmentation (computing) , myocyte , in vitro , biology , biochemistry , ecology
During limb regeneration in the newt, skeletal muscle provides a reservoir for uncommitted stem‐like blastema cells that participate in the replacement of the lost structure. However, it is not clear to what extent the activation of muscle‐associated satellite cells and/or fragmentation of multinucleate myofibers contribute to the blastema. During blastema formation, the composition of the extracellular matrix (ECM) undergoes dramatic changes that may provide cues for cell dedifferentiation. Using time‐lapse microscopy on in vitro cultures, we have shown that hyaluronic acid induces dedifferentiation and fragmentation of myotubes whereas fibronectin or matrigel leads to myotube formation. In addition to ECM composition, there are indications that the stiffness of the substrate is similarly important for cell behavior. We have created and mechanically characterized silicone‐based substrates that mimic the reported transverse stiffness of skeletal muscle, ~ 10 kPa. The behavior of newt myofibers over extended periods of time has been studied using these tunable substrates. By combining the appropriate ECM and substrate, we aim to create physiologically relevant environments to control satellite cell activation and/or muscle dedifferentiation. Supported by DARPA, NIH, Searle Funds