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

Background 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. Materials and methods There were 10 experimental groups (n = 6–8 rats/group). Bone marrow derived syngeneic MSCs (2 × 10 6 ; 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). Results 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. Conclusions 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.

Regenerative Strategies in Treatment of Peripheral Nerve Injuries in Different Animal Models

“… 1-At 16 weeks after surgery, none of the treatment groups show a significant reduction in the loss of gastrocnemius muscle mass. [ 82 ] 2-When compared to the control group 10, flexion contracture decreased in group 7 (Grade 1.2), which received G-CSF + BMSCs, and group 8 (Grade 1.8) which received Dihexa + BMSCs. Rabbit Brachial plexus (C5-T1) Bone marrow mesenchymal stem cell Expose roots of C5-T1 (ventral & dorsal) then torn off from the spinal cord 5×10 6 RFP-BMSCs were injected intraperitoneally Without conduit The recovery rate of the wet weight of the upper limb muscle, hematoxylin and eosin (HE)staining of injured tissue and electrophysiological measurement 3 weeks from surgery: 1-increased recovery rate of wet muscle weight ( p <0.05) [ 83 ] 2-The number of axons, myelinated fibers, and the density of nerve was raised 3-The levels of p-MAPK and p-ERK were lowered 4-The CMAP amplitude was reduced markedly ( p <0.05).…”