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One of the hopes of regenerative medicine is that one day we will be able to use stem cells to regrow damaged organs, avoiding the need for a transplant. It’s a fascinating idea, supported in part by the ability of some creatures, such as Axolotls and salamanders, to regrow parts of their anatomy that they have lost.
But there’s quite a leap from a lizard to a human and bridging that gap is proving far from easy. One of the problems is simply understanding how cells know what to do to form the correct shape for the organ. Even something as relatively simple as an ear is incredibly complex.
However, researchers at Harvard Medical School have discovered a way to replicate how cells form into flexible sheets, so they can be folded into the delicate shape of tubes in the inner ear. They did this by studying Zebrafish. Why? In an article in Genetic Engineering and Biology News Dr. Akankshi Munjal, PhD, first author of the paper, said the reason was simple.
“Zebrafish are transparent, so we just stick them under a microscope and look at this entire process from a single cell to a larva that can swim and has all its parts.”
Because they could watch the Zebrafish develop in real time, they were able to observe what the cells were doing at any point simply by looking at the fish under a microscope. Another advantage is that in Zebrafish the semicircular canals of the inner ear – tubes that help them maintain balance and orient themselves – form close to the surface, making it even easier to see what was going on.
In the study, published in the journal Cell, the researchers say it appears that a combination of pressure generated by hyaluronic acid, which acts as a cushion and lubricant between tissues, and molecular tethers between cells help direct flat sheets of cells into tubes and other shapes.
Dr. Sean Megason, one of the authors of the paper, said that knowing the mechanism at work is really important. “Right now tissue engineers are trying to build tissues without knowing how cells normally do this during embryonic development. We want to define these rules such that cells can be programmed to assemble into any desired pattern and shape. This work shows a new way in which cells can generate force to bend tissues into the right shape.”
The researchers say if they can understand how cells work together to create these complex shapes they may be better able to replicate that process in the lab, and grow ears, parts of ears or even other organs for people.
The Stem Cellar 
Stem cells are remarkable, can be used to regrow damaged organs and tissues. Current investigation showed that some tissues and organs require folding into variety of shaped for functioning. A combination of pressure generated by hyaluronate which act as a cushion and lubricant between tissues. Whereas molecular tether between cells help to direct flat sheet of cells into tube and other shapes. ECM rather than actinomyosin force to drive semicircular canal morphogenesis. ECM is rich in variety of growth factors, growth factors play key roles for cell-cell communication for growth differentiation and folding. Stem cells response to different growth factor to produce different types of cell. Different type of cells produce different strength to interact with other cells type. Thus, different mechanical forces, such as pressure of hyaluronate are required to fold different shapes of cell sheet. Polarization of tissues provides another kind of strength to hold together two different or similar cell sheets for easily folding. Therefore, mechanical anisotropy is needed to shape buds into tubes and polarized distribution of actinomyocin and t-cadlherin rich membrane tether. Hence, hyaluronate pressure shaped by anisotropy tissue stiffiness is an example of powerful force for morphogenesis.
All cells process growth factor receptors and distribution of specific growth receptors is varying from one cell type to the others. Hence, different cell types process different level of polarity. To note that, growth factors play key roles to generate specific cell type to take part in folding the cell sheets into variety of shaped.