Frogs with newly released legs that teach scientists how to regenerate bone marrow

Although they may go unnoticed, the ponds and wetlands around the world are filled with a large number of animals that have a lot to teach us about regenerative medicine. This is the case of axolotls or salamanderswho can regenerate their entire limbs after an amputation, or tadpoles, in which a similar phenomenon can also occur.

However, while the salamanders have this "superpower" throughout their lives, the tadpoles lose it as they become frogs, reaching a point where, in the best of cases, they can regenerate a kind of cartilaginous peak much thinner and weaker than the whole end. But this problem could end thanks to the work of a team of scientists from the Tufts University, which has developed a bioreactor capable of regenerating the ends of the African claw frogs (Xenopus laevis), also in adult specimens. Their results were published today at Reports on cells.

The least known function of progesterone

During the 19th century, the German physiologist Emil Du Bois-Reymond described in detail as the action of endogenous electric fields favored the development of some physiological phenomena, such as nervous excitement, muscle contraction and wound healing. This last has been much studied since then in the field of regenerative medicinein order to check if the application of exogenous electric fields, or techniques that enhance endogenous, it may be encouraged that tissue healing and regeneration take place more efficiently.

Among the researchers who have dedicated their work to this field is the doctor's team Michael Levin, principal author of the study that was published today. In the past, these scientists had succeeded in inducing the regeneration of the tail non-regenerative states of Xenopus, causing a bioelectric state through drugs. However, the frogs they were using at the time were still very young and, moreover, it was necessary to expose the whole body to bioelectric signaling.

Looking for a mechanism that can be used in adult frogs and specifically acting on the amputee area, they decided to introduce a new actor in the function: progesterone. For this, they have developed a silicon bioreactor printed in 3D, which was then filled with a hydrogel, composed of viscous mass of polymers. These compounds also joined together silk proteins, involved in tissue hydration and regeneration, e progesterone. This hormone is known for prepare the uterus hosting an embryo in case of pregnancy, but also has other less known functions, such as repair of nerves, blood vessels and bone tissue. Furthermore, it can regulate the bioelectric state of cells, through changes in ion flow and other signals associated with regeneration.

To carry out the study, the scientists divided recently amputated frogs into three groups: experimental, simulation and control. In the first two the amputee area is joined to the biorreactor, but only in the first has been added progesterone. As for control, we simply let the usual physiological processes follow their course, without any help. In the two cases in which the bioreactor was used, it was withdrawn twenty-four hours after its placement.

during nine and a half months the team followed the evolution of frogs, verifying that in those that belonged to the experimental group they had formed thicker limbs, with more developed bones and better vascularization and innervation. Moreover, they had easier to swim in the tanks that the rest, in which only the typical cartilaginous tip had been formed.

On the other hand, they also verified that there had been changes in the expression of some genes involved in signaling in the cells of the amputated zone. Some had increased their expression, while others had diminished it. It was particularly surprising, the decrease in regulation of the immune system. This suggests that progesterone must have stopped the body's natural defense reaction in a way that was positive for the regeneration process.

A discovery with the future

Based on these results, the team hopes to use this procedure for two purposes. On the one hand, it was proposed to use the bioreactor in mammals. That was found mice it can regenerate fingertips in optimal conditions, although its terrestrial conditions make it more complicated. If you look, most animals that have the natural ability to regenerate parts of their body are usually water And this actually makes sense, because a leg that hits the ground will regenerate worse and worse than one that simply floats in the water.

On the other hand, this type of phenomena that promote the bioelectrical processes of the body could also be used for purposes such as regeneration of spinal cord or the reprogramming of tumors. There is still a long way to go, but it could be a road with a great future. At present, the frogs treated by these scientists are already much easier to walk than the rest of their amputee comrades.

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