Stromalab - Targeting the stroma to regenerate Médecine régénératrice, thérapie cellulaire, cellules souches mésenchymateuses, tissu adipeux, moelle osseuse, réparation, régénération Regenerative medicine, cell therapy, mesenchymal stem cells, adipose tissue, bone marrow, repair, regeneration

Opioids inhibit tissue regeneration

In most mammals, the scarring process is fast-paced but alters the normal functioning of the tissue, unlike regeneration. In a study published in August 2018 in Scientific Reports, a team from the StromaLab laboratory (UMR 1031 – UT3 Paul Sabatier/EFS/ENVT/Inserm/ERL CNRS 5311), shows that the painkillers currently used are leading tissue repair towards scar healing and not regeneration. These results question about the actual pain relief strategy.

Regeneration is a complex biological process that allows an organism to restore a damaged tissue close to its original state. While spectacular examples exist in nature, such as the salamander capable of re-forming an entire limb after its amputation, regeneration in adult mammals is an exceptional phenomenon. In the vast majority of cases, the repair of an organ following a massive injury leads to scar healing that will frequently be associated with functional loss. From an evolutionary point of view, the scarring process leads more quickly to the reconstitution of a barrier against subsequent aggressions compared to the regeneration process.

In lower vertebrates, several elements seem to be essential for the regeneration process, including the quality of the inflammatory response and sensory innervation. While several recent publications have shown that the newborn rodent displays remarkable regenerative properties, these are quickly lost after birth to give way to scar healing. These results suggest that in higher vertebrates, inhibitory mechanisms of regeneration promote scarring process.

After developing a model of tissue regeneration in adult mammals, the StromaLab laboratory, known for its works on regenerative medicine, showed, in collaboration with Sophie Vriz's team at the Collège de France, that following tissue damage, the release of endogenous opioids modulates the inflammatory response which results in directing the repair process towards scarring and not regeneration. Therefore, in a spontanously scarring mouse, treatment with an opioid receptor antagonist, administered transiently and rapidly after the lesion, is sufficient to induce regeneration of the damaged tissue. This inhibitory role of endogenous opioids on regeneration was then validated in a completely different regeneration model in zebra fish.

These very original results show that the nociceptive system, the sensory alarm process that triggers the nerve message responsible for pain, could play a crucial role in regeneration processes. They also raise the question of the consequences of current analgesia protocols on repair processes. Indeed, opioids are known to limit nociceptive response and as such are routinely used in analgesic protocols.

A more precise definition of the time window and the subtypes of receptors involved should make it possible to redefine analgesic protocols that allow regeneration.

About the StromaLab laboratory :

The objective of the laboratory is to allow regeneration in adult mammals regardless of the tissue. Two tissues are being studied in particular: bone marrow and adipose tissue, in which research is focused on the role and functions of stem cells, including mesenchymal cells (MSC for bone marrow, ASC for adipose tissue) and their use in regenerative medicine.


Opioids prevent regeneration in adult mammals through inhibition of ROS production.
Labit E, Rabiller L, Rampon C, Guissard C, André M, Barreau C, Cousin B, Carrière A, Eddine MA, Pipy B, Pénicaud L, Lorsignol A, Vriz S, Dromard C, Casteilla L.
Sci Rep. 2018 Aug 15; 8(1):12170. DOI : 10.1038/s41598-018-29594-1.


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