Purpose: Prolonged denervation resulting from deferred nerve repair or long distance between the muscle and the repaired nerve, leads to major alterations concerning muscle fibre degeneration and their replacement by fibrous or fatty tissue. These structural modifications of the muscle are unfavourable for reinnervation and consequently affect the final functional outcome after peripheral nerve repair with its corollary of reduced muscle force. The purpose of this work was to assess the potential for regeneration of denervated-reinnervated muscles and their improvement with adjuvant cell therapy using in situ transfer of cultured autologus satellite cells.

Material and methods: This work was conducted with the tibialis anterior muscle in different groups of New Zealand rabbits. The experimental model was a sectioned common fibular nerve and immediate or deferred (two months) microsurgical nerve suture. In vivo functional measurements and histomorphological analyses were performed four months after nerve repair.

Results: Reinervation led to loss of mucle weight and maximal force (Fmax) which were greater with longer deferral of repair. Transfer of satellite cells performed immediately after reinervation did not improve muscle properties. Conversely, transfer of satellite cells two months after nerve suture increased Fmax 25% (p < 0.01) and muscle weight 28% (p = 0.005) in comparison with control muscles undergoing reinervation without cell transfer. Furthermore, the morphology of the muscle was improved as demonstrated by anti-myosine labelling studies.

Discussion: Adjuvant cell therapy allows, in certain conditions, an improvement in functional recovery after peripheral nerve injury. Its clinical application still raises a certain number of ethical issues but taking into consideration data currently available, it would be reasonable to propose this therapeutic approach in humans to reduce involution of the denervated muscle and improve its receptivity for regenerating axons after peripheral nerve repair. Better post-operative results could be expected

Purpose: Recovery of muscle function after nerve repair remains incomplete despite progress in microsurgical techniques. Potential for muscle recovery could be greatly improved. The purpose of our study was to demonstrate the functional impact of exogenous satellite cells in degenerated muscles.

Material and methods: We used the anterior tibialis muscle (Ta) in rabbits (n=24) as our experimental model. Muscle degeneration was created by bilateral injections of cardio-toxin into the Ta. Five days later, the left Ta was injected with autologous satellite cells (SC) at multiple points. The same volume of culture medium was injected into the right Ta. Two months later, maximal isometric muscle force and stress resistance of the Ta was measured. Histoimmuno-chemical labellings were made.

Results: The volume of cardiotoxin injected created two categories of muscles: recovery of former function was not possible with low dose cardiotoxin injections. Maximal isometric muscle force was less than 35% of the control. Transfer of SC restored nearly normal muscle force. Resistance to stress followed the same pattern. Recovery of maximal muscle force was possible with high-dose cardiotoxin injections. Resistance to stress was greater than the control (+ 35%). Transfer of SC did not modify results.

The weight of the Ta increased for both cardiotoxin doses. There was an increase in the size of the fibres with or without SC transfer.

Discussion: Injection of cardiotoxin induced muscle degeneration. With greater muscle degeneration, regeneration of muscle capacity was greater. Transfer of SC improved the functional result when muscle degeneration was incomplete. Improved resistance to stress after injection of high-dose cardiotoxin could result from changes in muscle myosin and fibrillary structure.

Conclusion: Further studies are needed before clinical application to better understand the underlying mechanisms operating with satellite cell injections. Many applications could be proposed, particularly for surgical nerve repair, ischaemic heart failure, and myopathy.