Intramuscular Stem Cell Injection in Combination with Bioengineered Nerve Repair or Nerve Grafting Reduces Muscle Atrophy.

ABSTRACT

BACKGROUND: Peripheral nerve injuries represent a clinical challenge, especially when they are accompanied by loss of neural tissue. In this study, the authors attempted to attain a better outcome after a peripheral nerve injury by both repairing the nerve lesion and treating the denervated muscle at the same time. METHODS: Rat sciatic nerves were transected to create 10-mm gaps. Repair was performed in five groups (n = 5 rats for each), as follows group 1, nerve repair using poly-3-hydroxybutyrate strips to connect the proximal and distal stumps, in combination with control growth medium injection in the gastrocnemius muscle; group 2, nerve repair with poly-3-hydroxybutyrate strip seeded with Schwann cell-like differentiated adipose stem cells (differentiated adipose stem cell strip) in combination with growth medium intramuscular injection; group 3, differentiated adipose stem cell strip in combination with intramuscular injection of differentiated adipose stem cells; group 4, repair using autograft (reverse sciatic nerve graft) in combination with intramuscular injection of growth medium; and group 5, autograft in combination with intramuscular injection of differentiated adipose stem cells. Six weeks after nerve injury, the effects of the stem cells on muscle atrophy were assessed. RESULTS: Poly-3-hydroxybutyrate strips seeded with differentiated adipose stem cells showed a high number of ßIII-tubulin-positive axons entering the distal stump and abundant endothelial cells. Group 1 animals exhibited more muscle atrophy than all the other groups, and group 5 animals had the greatest muscle weights and muscle fibers size. CONCLUSION: Bioengineering nerve repair in combination with intramuscular stem cell injection is a promising technique to treat nerve lesions and associated muscle atrophy. CLINICAL RELEVANCE STATEMENT Nerve injuries and resulting muscle atrophy are a clinical challenge. To optimize functional recovery after a nerve lesion, the authors treated the nerve and muscle at the same time by using regenerative medicine with adipose stem cells and obtained encouraging results for future clinical applications.