Facebook PixelAn experiment to fully regenerate a frog's limb using exosomes from an axolotl's limb bud blastema
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An experiment to fully regenerate a frog's limb using exosomes from an axolotl's limb bud blastema

Image credit: James Monaghan laboratory/Northeastern University

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Darko Savic
Darko Savic Sep 11, 2021
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Feasibility

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Necessity

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Can exosomes transplanted from an axolotl's limb bud blastema to a frog's limb bud blastema fully regenerate the frog's limb?

Axolotls are known for their ability to fully regenerate parts of their body after amputation. Adult frogs are capable of partial limb regeneration. Their amputated limbs regenerate into spikes rather than full limbs.

Why do this experiment?

A frog is already halfway there to full regeneration capability. Exosomes extracted from axolotl limb blastema cells might do what it takes to achieve full regeneration. The next step is to try it on a mouse. Eventually, this could become a component in limb regeneration therapy for humans.

Someday such exosomes could be lab produced en-masse and used for therapeutic purposes.

[1]Satoh A, Ide H, Tamura K. Muscle formation in regenerating Xenopus froglet limb. Dev Dyn. 2005 Jun;233(2):337-46. doi: 10.1002/dvdy.20349. PMID: 15768391.

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Experiment on mice along the same lines

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Darko Savic
Darko Savic Sep 13, 2021
Mammalian embryos before a certain age have the ability to regenerate.

Adult mice don't have the ability to regenerate limbs after amputation.

Experiment:

On a genetically identical line of mice, would an embryonic limb bud grafted onto an adult mouse's place of amputation grow into a normal limb? Would it help if the amputation site was treated with exosomes from a regenerating axolotl limb bud blastema? A suitable environment would of course have to be maintained around the amputation spot.

[1]Lee KK, Chan WY. A study on the regenerative potential of partially excised mouse embryonic fore-limb bud. Anat Embryol (Berl). 1991;184(2):153-7. doi: 10.1007/BF00942746. PMID: 1952102.

[2]Gardiner DM. Ontogenetic decline of regenerative ability and the stimulation of human regeneration. Rejuvenation Res. 2005 Fall;8(3):141-53. doi: 10.1089/rej.2005.8.141. PMID: 16144469.

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A bit easier experiment that could possibly give hope for your experiment to work

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J
Juran Sep 15, 2021
Hi Darko! In my humble opinion, the idea has potential. Blastema seems to somehow limit the full regeneration in frogs.

I found a team of researchers that did the opposite. Their main theory was that the blastema cells of the frog have a different cell environment which limits them to "go back" and form undifferentiated blastema capable of full limb regeneration.
They transplanted blastema cells of adult Xenopus frog into developing limb buds of tadpoles. The results showed that even in a permissive embryonic environment, where the host's blastema cells fully regenerate the limb, the adult blastema cannot regenerate a functional limb. As they say "The cells remained unresponsive and did not contribute to forming a limb, revealing their intrinsic inability to be reprogrammed".

I wonder why they didn't do the opposite - transplant the tadpole blastema to a frog limb blastema, which is close to what you proposed. I would first do this and then disassemble the components and search for the key players (here comes the exosome). Why? Because, as I realized, extraction and purification of exosomes is a tough work, so this way, we could save money and time.

[1]https://www.sciencedirect.com/science/article/pii/S1534580721003543?via%3Dihub

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