Stem cell, Granulocyte-Colony Stimulating Factor and/or Dihexa to promote limb function recovery in a rat sciatic nerve damage-repair model: Experimental animal studies

Abstract

Optimizing nerve regeneration and re-innervation of target muscle/s is the key for improved functional recovery following peripheral nerve damage. We investigated whether administration of mesenchymal stem cell (MSC), Granulocyte-Colony Stimulating Factor (G-CSF) and/or Dihexa can improve recovery of limb function following peripheral nerve damage in rat sciatic nerve transection-repair model. There were 10 experimental groups (n = 6-8 rats/group). Bone marrow derived syngeneic MSCs (2 × 106; passage≤6), G-CSF (200-400 μg/kg b.wt.), Dihexa (2-4 mg/kg b.wt.) and/or Vehicle were administered to male Lewis rats locally via hydrogel at the site of nerve repair, systemically (i.v./i.p), and/or to gastrocnemius muscle. The limb sensory and motor functions were assessed at 1-2 week intervals post nerve repair until the study endpoint (16 weeks). The sensory function in all nerve boundaries (peroneal, tibial, sural) returned to nearly normal by 8 weeks (Grade 2.7 on a scale of Grade 0-3 [0 = No function; 3 = Normal function]) in all groups combined. The peroneal nerve function recovered quickly with return of function at one week (∼2.0) while sural nerve function recovered rather slowly at four weeks (∼1.0). Motor function at 8-16 weeks post-nerve repair as determined by walking foot print grades significantly (P < 0.05) improved with MSC + G-CSF or MSC + Dihexa administrations into gastrocnemius muscle and mitigated foot flexion contractures. These findings demonstrate MSC, G-CSF and Dihexa are promising candidates for adjunct therapies to promote limb functional recovery after surgical nerve repair, and have implications in peripheral nerve injury and limb transplantation. IACUC No.215064.