01.13 Stem Cell and Granulocyte Colony Stimulating Factor to Promote Recovery in a Limb Transplant Model

K. Kniery1, M. DeHart1, S. Salgar1  1Madigan Army Medical Center,Clinical Investigation,Tacoma, WA, USA

During the global war on terrorism (2001-2008) in Iraq and Afghanistan, 737 US military service members sustained major limb amputations. Limb transplantation offers hope to improve the quality of life. We investigated whether mesenchymal stem cell (MSC) and G-CSF therapy can improve functional recovery in nerve transection-repair and limb transplant models.

Under general anesthesia the sciatic nerve branches (tibial, peroneal and sural) were transected and repaired.  In another group, syngeneic right hind limb transplantation was performed. MSCs (5×106; passage ≤6), G-CSF (50µg/kg), or Vehicle were administered topically and i.v./i.p. 

At two weeks post-nerve repair, sensory function (SF) in all groups was ~1.5 on a scale of Grade 0-3 (0=No function; 3=Normal function).  By 4 weeks it was 2.2±1.0, 2.0±1.2, and 1.8±1.3 in MSC, G-CSF and Vehicle treated groups, respectively. By 10 weeks, normal SF (~3) was restored in all groups (n=8/group). The sciatic nerve function index (SFI) a measure of motor function (0=normal; -100 =nonfunctional) during 5-16 weeks was markedly improved in G-CSF (-40 to -26) compared to MSC (-93 to -66) or Vehicle (-110 to -45) group (Figure1). In limb transplants, SF recovery ranged 0.8-1.3 by 8 weeks, and 1.5-2.0 by 16 weeks post-surgery.  Limb transplants (~60%) developed flexion-contractures and we were unable to calculate SFI. Fewer animals in G-CSF (37%) compared to Vehicle (66%) group developed contractures. Gastrocnemius muscle atrophy was evident in limb transplants. 

G-CSF and MSC therapies appear to promote sensory and motor function recovery in nerve transection-repair and limb transplant models.