Question

1a)Explain cell-matrix interactions. Why they are important for the control of growth and development of tissue engineered product?

1b)b. What is the relation between a material surface and cell fate?

Answer 1

1)

• The extracellular matrix not only provides structural support and stability but also provides various biochemical and tactile cues. These cues are extremely important for tissue differentiation, morphology, and oftentimes, continued survival.
• The ECM as the name implies is composed of proteins that serve as scaffolds for tissue. Examples are collagen, fibronectin, pectin, and a plethora of others.
• This matrix forms a mechanically resistant mesh that holds tissues in place, the heterogeneous makeup of many organs would not be possible without the organizational qualities of the ECM.
• So how does the ECM control tissue growth, morphology, and homeostasis?
• The ECM binds growth factors, interacts with cell-surface receptors, and directs the signal-transduction and the transcriptional control of certain cells.
• Let’s consider a tissue engineering model which contains epithelial cells.
• Simple glandular epithelial cells have an apical/ basal polarity. This maintenance of polarity is of high biological consequence. This is maintained by cellular interactions with Fibrocytes, Adipocytes, and Leukocytes. The cells need factors in the ECM to bind to the basal side to drive this polarity.
• The ECM also plays a major role in differentiation. Both mechanical cues and growth factors such as EGF, BDNF, etc, push cells into certain lineages. This is of particular interest in cell culture with Induced pluripotent stem cells.
• For example, manipulating the elasticity of mesenchymal stem cells determines its cell fate.
• To sum it up, the ECM can decide cell fate, cell morphology, cell lineage, cell homeostasis.
• By growth factors, integrin binding, biomechanical cues, and structural proteins.
• This is obviously of use in tissue engineering, as we can use ECM scaffolds and constructs such as cell sheet technology to manipulate our cultured cells into our preferred morphology, cell fate and are sometimes compulsory to preserve their health.

2) This phenomenon is called as the relationship between substrate topology and cell fate determination.

• For example, Mesenchymal stem cells when cultured depending on surface stiffness have a range of cell fates. Soft substrates induce neurogenesis, intermediate substrates induce myogenesis and stiff substrates induce osteogenesis. The working hypothesis is that the stiffness faced by the native tissue in the body is a cell fate determinant.
• Also, ligands coating the surface are very important, collagen 1 coatings along with a particular stiffness promoted myogenesis.
• The cell fates are also defined by topography, whether it is rough, smooth, or striated all of these have some bearing on cell differentiation. Electrospun nanofibers promote neural stem cell differentiation.