Paralyzed mice walk again thanks to a transplant of human cells

Israeli researchers have made paralyzed mice walk again by transplanting them with spinal cord cultured from human cells. An impressive result which confirms the spectacular progress observed in recent months.

Recently, American researchers managed to restore the use of their limbs to paralyzed mice thanks to a new approach based on a network of nanofibers. Today, an Israeli team has achieved a comparable result thanks to a very different approach, and perhaps even more promising in the context of human medicine.

In their work published in the prestigious journal Science Advances, researchers from the Sagol Center for Regenerative Biotechnolgy in Tel Aviv presented a new technique that allowed them to reconstruct human spinal cord tissue and implant it in paralyzed mice. At the end of the protocol, 80% of them recovered their ability to walk.

The result may be comparable to that of the Northwestern University team, but the method is fundamentally different since it is based directly on stem cells from the human line, and not on entirely artificial nanofibers. To achieve this, there is no need for state-of-the-art materials; a small sample of fat is enough.

Rewrite the history of cells

The researchers then separated the cells from the surrounding tissue in order to reprogram them. They then subjected them to manipulation in an effort to bring them back to an earlier stage of development, before they had specialized to fulfill a particular role. They then return in a state relatively close to embryonic stem cells (we speak of a pluripotent stem cell), and therefore literally benefit from a second youth. From this stage, they are therefore able to take another path of development and produce another type of cell. It remains only to force them to take the desired path.

In the human body, this process of determination is the consequence of an infinitely complex set of chemical signals – the morphogens – produced in the different tissues. During development, the combination of these different signals will determine the nature and layout of all the structures of the body: this is called morphogenesis. For example, there is a signal that manages the arrangement of tissues on the antero-posterior axis, that is to say from head to toe; the cells less exposed to this morphogen during development will end up on the side of the head, and the others will migrate towards the other pole.

It is thanks to the accumulation of these many signals that the body can set up your organizational plan on a global scale, then on the scale of the various connective, muscular, nervous, or other tissues. For researchers, the whole challenge is therefore to expose their stem cells to the precise combination of signals that allow, very briefly, to tell the cells: “you will become spinal cord cells”.

From the human cell to the personalized implant

To achieve this, they started by recycling leftover material that was separated in the first step to produce a custom hydrogel. This is a very important step; since this material is from the same organism, the resulting hydrogel will not be considered an invader by the immune system. There is therefore no risk of a rejection reaction. This is a concept already explored in many works that work on custom organ culture.

In this context, this hydrogel which served as a substrate for them to transmit morphogens. They were thus able grow small portions of human spinal cord. These sections were then transplanted into paralyzed mice, some for a long time (chronic models) and others recently (acute models). At the end of the experiment, 80% of the chronic models and 100% of the acute models had regained their ability to walk.

Work full of promise

This is a particularly encouraging result. Indeed, almost the entire procedure would technically be already transferable to humans. This is a significant advantage that should significantly accelerate the large-scale development of a clinical procedure. The researchers also hope to move to this stage as soon as possible. They are currently discussing a preclinical protocol with the US administration, and hope to be able to move to a clinical trial by “some years”.

In any case, it would be a real medical revolution. Work of this type already promises to transform the daily lives of many people suffering from spinal cord injuries, whether of pathological or traumatic origin. And the delay announced by the researchers seems far from unreasonable. In the past few months alone, we have seen everything bloom a bunch of sensational projects on this subject. One thinks in particular of the other works mentioned at the beginning of the article. One can also cite other approaches based on brain-machine interfaces which are also beginning to progress; we remember, for example, that in December 2021, a paralyzed man was able to post his first tweet thanks to a brain chip. Hopefully, even paraplegics will be able to applaud these tremendous advances with both hands in the relatively near future.

The text of the study is available here.

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