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I just sat through one of the simplest and most logical talks.
Dr. Elly Tanaka, from Heidelberg, took the stage in the plenary session and described an incredible set of data that her lab has generated to understand the molecules involved in limb regeneration – a longstanding dream of the regenerative medicine field.
Dr. Tanaka showcased the power of studying the salamander and its natural regenerative capacity. As readers may or may not know, the salamander can regenerate its own limbs. You can watch an excellent video and explanation of this process on the Howard Hughes Medical Institute website.
Very cool, right?
In the video you just watched, the blastema is the group of cells responsible for all this regeneration. Everything is somehow organized in order to generate the fully functional limb. The big question that Dr. Tanaka pitched to the crowd was whether or not we could really understand the complicated mixture of bone cells, muscle cells and nerve cells, and how they coordinate themselves to form a fully functional new limb.
Of course, Dr. Tanaka was not the first to have the idea to learn from nature’s regenerative specialists and she catalogued previous work from international colleagues who have shown that the nerve cells are critical to the process (and their removal disabled the regenerative machinery) and demonstrated the principle of “positional discontinuity” by transplantation of the left side’s cells to the right side – a procedure which results in the generation of three limbs on one side. Without going into too much detail, this line of experimentation eventually showed that both sides of the limb (the front (anterior) and back (posterior)) had to interface properly in order to generate an appropriate limb.
Dr. Tanaka used this oddity to her advantage as her laboratory attempted to identify, in a step-by-step process, the molecules driving this activity. She presented a series of transplantation experiments, chemical stimulus experiments and genetic rescue experiments (where you give the deficient cells the gene you suspect is lacking to “rescue” the defect) that interrogate the process one molecule at a time. Basically, each potential piece of the puzzle was tested to see if it could permit correct limb regeneration in the wrong setting; for example, could they make the “front” cells think they were “back” cells?
Through this process, they identified several key molecules for determining the success of the regenerative process. Dr. Tanaka even goes on to demonstrate the interactivity of these molecules showing that once expressed, they reinforce the expression of each other forming a tight network that drives regeneration.
Overall though, I suspect you readers are probably most interested in what this type of study means for regenerative medicine. In principle, the component bits required for limb regeneration would also be present in the remaining limb bud in other organisms, including humans. Perhaps all that would be required is to provide the right trigger for helping the cells remember what they were?
Dr. Tanaka’s work is the first step to understanding which molecules (and their mammalian counterparts) might be the best candidates to drive limb regeneration in animals that are not typically able to do so. It may sound like science fiction at this point, but understanding the fundamental building blocks found in nature’s best examples of regeneration seems a pretty good place to start.
For readers who want more information on limb regeneration in general, Dr. Tanaka has written a clear scientific review on the subject here.
Watch for my second post from ISSCR on Monday (June 29) on Signals.
David Kent
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