*Purpose: Recently, transplantation of hand and face has become a new clinical specialty. The objective of this study was to determine whether adult Mesenchymal Stem Cells (MSCs), Granulocyte-Colony Stimulating Factor (G-CSF) and/or Dihexa can promote limb transplant function.

*Methods: We used rat sciatic nerve transection-repair model. There were 10 experimental groups (n=6/group). Bone marrow derived syngeneic MSCs (2 million), G-CSF (50-100µg/kg), (Dihexa 2-4mg/kg) and/or Vehicle were administered locally via hydrogel at the site of nerve repair, i.v./i.p., and to gastrocnemius muscle.

*Results: Total sensory function was ~1.4, 1.7, 2.7 and 2.9 at 2, 4, 8 and 16 weeks post-nerve repair, respectively, on a scale of Grade 0-3 (0=No function; 3= Normal function) in all groups combined; peroneal nerve function recovered quickly by one week (~2.0) and sural nerve function recovered slowly by four weeks (~1.0). Motor function at 16 weeks post-nerve repair as determined by walking foot print grades 0-4 (0=no print; 4=heel plus 4-5 toe prints) was 3.0±0.9, 3.0±0.8, and 2.0±0.6 in MSC+G-CSF, MSC+Dihexa and MSC+vehicle groups with gastrocnemius injections, respectively; however, without gastrocnemius injection it was ~1.6. G-CSF or Dihexa injections to gastrocnemius significantly (P<0.05) improved motor function, mitigated muscle atrophy and reduced flexion contractures. MSCs expanded ex vivo were CD29+, CD90+, CD34-, CD31-, MHC Class I+, Class II- and multipotent. In a parallel study with tibial nerve repair we observed significant nerve regeneration/myelination with MSC therapy (n≥6).

*Conclusions: It appears, MSC, G-CSF and Dihexa are promising candidates for adjunct therapies to promote limb transplant function.

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