Effect of genetically modified Schwann cells with increased motility in end-to-side nerve grafting.
Taking into account that Schwann-cell (SC) motility is a prerequisite for myelination during peripheral nerve regeneration, the present study was designed with the intention to increase SC motility in vitro and to evaluate the effect of transduced SC on nerve regeneration in vivo, through silicone tubes after end-to-side nerve repair. Our in vitro study demonstrated that SC transduction with the pREV-HW3 retrovirus, encoding for sialyl-transferase-X (STX), significantly increased their motility compared to the control. In the in vivo study, 45 Wistar rats were randomized into three groups of 15 each. In all animals, the left peroneal nerve was severed, and a 10-mm segment was removed. The distal stump of the peroneal nerve was connected end-to-side to a perineurial window in the ipsilateral tibial nerve with either a silicone tube lined with SC (group A) or a silicone tube lined with STX-transduced SC (groups B and C). Fluorescence and light microscopy in group C showed that SCs were viable the first critical 15 postoperative days. After 90 days, light microscopy in group B demonstrated that STX-transduced SCs with increased motility ensured nerve regeneration, through silicone tubes, in all cases. Furthermore, STX-transduced SCs increased significantly fiber diameter and myelin thickness, and most importantly enhanced significantly the functional outcome compared to non-transduced SCs.
Gravvanis
Andreas I
AI
Department of Plastic Surgery, Microsurgery and Burns Center, General State Hospital of Athens G. Gennimatas, Athens, Greece. gravvani@yahoo.com
Lavdas
Alexandros
A
Papalois
Apostolos E
AE
Franceschini
Isabelle
I
Tsoutsos
Dimosthenis A
DA
Dubois-Dalcq
Monique
M
Matsas
Rebecca
R
Ioannovich
John D
JD
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D005821:Genetic Techniques; D066298:In Vitro Techniques; D008297:Male; D023421:Models, Animal; D009416:Nerve Regeneration / Q000235:genetics* / Q000502:physiology; D010525:Peripheral Nerves / Q000502:physiology / Q000637:transplantation*; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000502:physiology*