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Biology subjects

Parker, K. K.

Publications and source records attributed to Parker, K. K..

2 recordsLinked to original sources

Structure-Function in Helical Cardiac Musculature Using Additive Textile Manufacturing

For more than fifty years, it has been hypothesized that the helical alignment of the heart gives rise to its mechanical function. Testing this hypothesis in an engineered environment is difficult, as the fine spatial features and complex three-dimensional (3D) structures of the cardiac musculature are challenging to reproduce using current biofabrication techniques. Addressing this, here we report a new form of additive textile manufacturing, Focused Rotary Jet Spinning (FRJS). FRJS allows for the rapid manufacturing of micro/nanofibers with controlled alignments. Using this method, we manufacture 3D models of the left ventricle, showing that helically aligned scaffolds display increased strain uniformity, axial shortening, cardiac output, and ejection fractions as compared to circumferential models. We then demonstrate how FRJS can enable the assembly of a full-sized model of the human hearts musculature. This work experimentally confirms that ventricular alignment plays a critical role in ensuring healthy cardiac performance.

bioengineering

Prednisolone rescues Duchenne Muscular Dystrophy phenotypes in human pluripotent stem cells-derived skeletal muscle in vitro

Duchenne Muscular Dystrophy (DMD) is a devastating genetic disease leading to degeneration of skeletal muscles and premature death. How dystrophin absence leads to muscle wasting remains unclear. Here, we describe an optimized protocol to differentiate human induced Pluripotent Stem Cells (iPSC) to a late myogenic stage. This allows to recapitulate classical DMD phenotypes (mislocalization of proteins of the Dystrophin-glycoprotein associated complex (DGC), increased fusion, myofiber branching, force contraction defects and calcium hyperactivation) in isogenic DMD-mutant iPSC lines in vitro. Treatment of the myogenic cultures with prednisolone (the standard of care for DMD) can dramatically rescue force contraction, fusion and branching defects in DMD iPSC lines. This argues that prednisolone acts directly on myofibers, challenging the largely prevalent view that its beneficial effects are due to anti-inflammatory properties. Our work introduces a new human in vitro model to study the onset of DMD pathology and test novel therapeutic approaches.

cell biology