Hi folks, I'm back! A few weeks off to write my Ph.D. dissertation and graduate last week sure kept me busy but it has been nice to reflect on my research and time in graduate school.
As promised, this week’s science article pick of the week is on a very fascinating problem: regeneration. It’s remarkable that some organisms like salamanders, lizards, starfish, jellyfish and flatworms have the capacity to regenerate organs and/or body parts after amputation! Scientists hope that studying these animals will teach us about tissue repair that we may be able to utilize for human medicine by developing treatments for muscular dystrophy, neurodegenerative diseases, cardiovascular diseases, diabetes and cancer.
One of the most impressive model systems to study tissue regeneration has been of limb regeneration in salamanders. It’s remarkable that after losing a limb, salamanders can regenerate missing body parts like the skin, muscle, bone, blood vessels and neurons! Some of these animals regenerate so well it’s hard to tell that these animals had an injury – which contrast to the scarring that people get after tissue injury. It’s such a fascinating process that great thinkers including philosophers like Aristotle and Voltaire and biologists like Charles Darwin and Thomas Hunt Morgan have all wondered about the mechanisms underlying tissue regeneration, and it still remains a large mystery in the biology community, but much progress has been made in recent years.
One of the greatest challenges in the field of tissue regeneration has been to understand how cells in the mature, unamputated tissue give rise to new, differentiated cells like bone, neurons, skin, etc. that make up the regenerating limb. For a long time, scientists knew that after limb amputation in the salamander, a cluster of cells form a blastema, a temporary mass of cells that is necessary to regenerate the limb. Since these blastema cells look identical to each other when you examine cell morphology, it was long thought that these cells are identical, and thus must be pluripotent cells, capable of giving rise to all the mature cell types in the regenerate limb. However, the article pick of this week demonstrates that looks can be deceiving; rather, the blastema is composed of a mixed population of cells that remember what cell type they came from and generally only give rise to that cell type in the regenerating limb!
How did the scientists figure this out? They studied limb regeneration in the axolotl, Ambystoma mexicanum. They use a transgenic axolotl that has a gene encoding green fluorescent protein (GFP) so the animals are fluorescent. The scientists take tissue grafts from this green fluorescent animal and transplant the graft to a wild type animal (that is not fluorescent). This strategy enables scientists to track the fluorescent cells – what they become and where they end up after limb amputation. When they amputate the host axolotl limb, they can follow where the green fluorescent cells end up during limb regeneration and what cell types they rebuild.
The scientists found that upon limb amputation, the labelled muscle cells only give rise to regenerate muscle cells, skin cells only give rise to skin cells, and neurons only give rise to neurons. This tells us that the cells from the unamputated tissue that form the blastema are not pluripotent cells but rather progenitor cells with restricted developmental potential to help rebuild the limb. This study has important implications for regenerative medicine because the finding that differentiated cells only have to take a step back to begin proliferating again to rebuild tissues rather than taking many steps back to de-differentiate into a ‘jack of all trades’ stem cell is not necessary for tissue repair. Lots of scientists are interested in stem cells and induced pluripotent stem (iPS) cells to understand tissue repair and regeneration, but studies like this one add a new element to our current understanding and can provide alternative strategies to help develop regenerative therapies.
For free access to the original report, click here.