Natural conduits for bridging a 15-mm nerve defect: comparison of the vein supported by muscle and bone marrow stromal cells with a nerve autograft.
OBJECTIVE
The gold standard for reconstructing large nerve defects, the nerve autograft, results in donor-site morbidity. This detrimental consequence drives the search for alternatives. We used a vein filled with a small piece of fresh muscle to prevent the vein from collapsing and with bone marrow stromal cells (BMSCs) to enhance regeneration.


METHODS
In 60 rats, a 15-mm sciatic nerve defect was bridged with a nerve autograft, a vein filled with muscle or a vein filled with muscle and BMSCs. Toe spread and pinprick were used to evaluate motor and sensory function. Compound muscle action potentials (CMAPs) and the gastrocnemius muscle index (GMI) were recorded to assess conduction properties and denervation atrophy. Extensive histology was performed to confirm presence of BMSCs and to evaluate regeneration by staining neural tissue for Schwann cells and neural growth factor.


RESULTS
After 12 weeks, all animals responded with toe spread and pinprick reaction; significant differences were found between groups. Six weeks post grafting no difference was found comparing the GMI between the groups. Group I had a significant increase in GMI at 12 weeks compared to group II and group III. The CMAP measurements showed comparable results at 6 weeks post grafting. Twelve weeks after reconstruction, group I had significantly better results compared to group II and group III. Group III showed a tendency to outperform group II at 12 weeks postoperatively. Immunofluorescence analysis showed an increased number of Schwann cells in group III compared to group II. The BMSCs were visible 6 and 12 weeks postoperatively.


CONCLUSIONS
This study is a step forward in the search for an alternative to the nerve autograft because it demonstrates the beneficial effect of BMSCs to a conduit. However, our data do not demonstrate sufficient benefit to warrant clinical implementation at this stage.
Department of Plastic, Reconstructive and Hand Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. t.nijhuis@erasmusmc.nl
Tim H J
TH
Nijhuis
Corneel W J
CW
Bodar
Johan W
JW
van Neck
Erik T
ET
Walbeehm
Maria
M
Siemionow
Maria
M
Madajka
Joanna
J
Cwykiel
Joleen H
JH
Blok
Steven E R
SE
Hovius
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival; D059630:Mesenchymal Stem Cells; D018482:Muscle, Skeletal / Q000637:transplantation*; D009416:Nerve Regeneration / Q000502:physiology; D016067:Nerve Transfer / Q000379:methods*; D059348:Peripheral Nerve Injuries / Q000601:surgery*; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D019651:Plastic Surgery Procedures / Q000379:methods; D012584:Sciatic Nerve / Q000293:injuries / Q000601:surgery*; D012680:Sensitivity and Specificity; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014680:Veins / Q000601:surgery / Q000637:transplantation*