The Third Dimension of Tissue Engineering

We are somewhere in the middle of the ten year period in which researchers establish practical methodologies for growing three-dimensional, complex, structured tissue from a patient's own stem cells. The difficulty of moving from the two dimensions of the petri dish cell culture to fully functioning three-dimensional tissue should not be understated: how to build the right sort of supporting scaffolding with features at the nanoscale, how to incorporate the required capillary network to supply the cells with oxygen and nutrients, how to ensure that different cell types are arranged as they would be in natural tissue, and so on. This is the sort of many-faceted problem that requires a large scientific community and a great deal of investment to solve in any reasonable amount of time - fortunately both exist in this case. Other areas of life science research and medical development should be so lucky.

So far decellularization shows great promise, and has been used in a number of human transplant surgeries, but still requires a donor organ to supply the complex scaffolding of the extracellular matrix. Research groups have also demonstrated the ability to build a few structures that are much simpler than natural organs, but which can still perform some of the required tasks adequately - such as the tissue engineered bladders produced by Tengion.

There is a way to go yet, however. Here is a popular science article from Cosmos Magazine that examines the third dimension of tissue engineering - still novel, exploratory, and new:

Since the 1950s, scientists have probed the molecular secrets of cells plucked from the body and grown in the laboratory on flat plates or Petri dishes. These standard cultures have taught us about normal cell biology, cancer and other diseases.From a cell's point of view, however, these 2-D habitats - dubbed 'plastic palaces' by one researcher - are a poor substitute for real life. Scientists have come to realise that a cell's surrounding microenvironment plays a much larger role in directing its growth and shaping its behaviour than anyone understood 10 or 20 years ago.

In the body, cells are accustomed to living large, in three dimensions, embedded within an extracellular matrix (ECM). Through the pores of the fibrous ECM, a cell is bathed in nutrients and signalling molecules. A thin basement membrane anchors the cell to surrounding connective tissues and emits chemical signals that regulate some cell processes. In addition, physical forces push and pull the cell from all directions.

Without this extracellular community, cells grown in single layers on standard flat cultures will proliferate, but they usually don't differentiate into specialised cells forming structures such as capillaries. They can be inadequate models yielding misleading results.

It's easy to take for granted the less lauded hurdles overcome by researchers along the way to building replacement human organs on demand - moving from two-dimensional cell cultures to three-dimensional structures was one of them. Easy to say, far harder to accomplish.

Comments

I'm very intrigued by the idea that all aging can be reduced to signalling errors. The importance of signalling is rearing its head more and more - think of the biological analogy of Hansonian social signaling theory.

Important clues are emerging here to support a grand signalling theory. For instance, in a recent post you mentioned that the growth factors (which are basically chemical signallers) cytokines (of which hormones are a special case) might be the main benefit of stem cells. And there was another recent result you mentioned that young blood was found to have beneficial effects.

Is physical entropy just a special case of informational entropy? Is decision theory just a special case of information theory? And is Bayesian induction just a special case of categorization in an informational feature space?

I strongly suspect the answer to all three questions is yes, and the pertinent point here is the possibility of a grand signalling theory of aging, where physical entropy is understand as a special case of signaling errors (information entropy).

It all strongly points to cytokines and hormones as the key to aging. Are you listening Aubrey? ;)

Posted by: zarzuelazen at November 13th, 2010 8:05 PM

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