Extracellular matrix signaling in morphogenesis and repair.

The extracellular matrix (ECM) is critically important for many cellular processes including growth, differentiation, survival, and morphogenesis. Cells remodel and reshape the ECM by degrading and reassembling it, playing an active role in sculpting their surrounding environment and directing their own phenotypes. Both mechanical and biochemical molecules influence ECM dynamics in multiple ways; by releasing small bioactive signaling molecules, releasing growth factors stored within the ECM, eliciting structural changes to matrix proteins which expose cryptic sites and by degrading matrix proteins directly.

Developing cardiac and skeletal muscle share fast-skeletal myosin heavy chain and cardiac troponin-I expression.

Skeletal muscle derived stem cells (MDSCs) transplanted into injured myocardium can differentiate into fast skeletal muscle specific myosin heavy chain (sk-fMHC) and cardiac specific troponin-I (cTn-I) positive cells sustaining recipient myocardial function. We have recently found that MDSCs differentiate into a cardiomyocyte phenotype within a three-dimensional gel bioreactor. It is generally accepted that terminally differentiated myocardium or skeletal muscle only express cTn-I or sk-fMHC, respectively.

Engineered fetal cardiac graft preserves its cardiomyocyte proliferation within postinfarcted myocardium and sustains cardiac function.

The goal of cellular cardiomyoplasty is to replace damaged myocardium by healthy myocardium achieved by host myocardial regeneration and/or transplantation of donor cardiomyocytes (CMs). In the case of CM transplantation, studies suggest that immature CMs may be the optimal cell type to survive and functionally integrate into damaged myocardium. In the present study, we tested the hypothesis that active proliferation of immature CMs contributes graft survival and functional recovery of recipient myocardium.

Directed stem cell differentiation: the role of physical forces.

A number of factors contribute to the control of stem cell fate. In particular, the evidence for how physical forces control the stem cell differentiation program is now accruing. In this review, the authors discuss the types of physical forces: mechanical forces, cell shape, extracellular matrix geometry/properties, and cell-cell contacts and morphogenic factors, which evidence suggests play a role in influencing stem cell fate.

A three-dimensional gel bioreactor for assessment of cardiomyocyte induction in skeletal muscle-derived stem cells.

Skeletal muscle-derived stem cells (MDSCs) are able to differentiate into cardiomyocytes (CMs). However, it remains to be investigated whether differentiated CMs contract similar to native CMs. Here, we developed a three-dimensional collagen gel bioreactor (3DGB) that induces a working CM phenotype from MDSCs, and the contractile properties are directly measured as an engineered cardiac tissue.

Engineered early embryonic cardiac tissue increases cardiomyocyte proliferation by cyclic mechanical stretch via p38-MAP kinase phosphorylation.

Cardiomyocyte (CM) transplantation is one therapeutic option for cardiac repair. Studies suggest that fetal CMs display the best cell type for cardiac repair, which can finitely proliferate, integrate with injured host myocardium, and restore cardiac function. We have recently developed an engineered early embryonic cardiac tissue (EEECT) using embryonic cardiac cells and have shown that EEECT contractile properties and cellular proliferative response to cyclic mechanical stretch stimulation mimic developing fetal myocardium.