Ghrelin and adipose-derived mesenchymal stromal cells improve nerve regeneration in a rat model of epsilon-caprolactone conduit reconstruction.
OBJECTIVE
Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of adipose-derived mesenchymal cells (ASCs) and ghrelin (GHR), a neuropeptide with neuroprotective, trophic, and developmental regulatory actions, on peripheral nerve regeneration in a model of severe nerve injury repaired with nerve conduits.


METHODS
The right sciatic nerves of 24 male Wistar rats were 10-mm transected unilaterally and repaired with Dl-lactic-ε-caprolactone conduits. Rats were then treated locally with saline, ASCs, or GHR. At 12 weeks post-surgery, we assessed limb function by measuring ankle stance angle and percentage muscle mass reduction and evaluated the histopathology, immunohistochemistry, ultrastructure, and morphometry of myelinated fibers.


RESULTS
Rats receiving GHR or ASCs showed no significant increased functional recovery in ankle stance angle (p=0.372) but a higher nerve area (p=0.015), myelin area (p=0.046) and number of myelinated fibers (p=0.012) in the middle and distal segments of operated sciatic nerves in comparison to saline-treated control animals.


CONCLUSIONS
These results suggest that utilization of ghrelin or ASCs may improve nerve regeneration using Dl-lactic-ε-caprolactone conduits.
Hand Surgery Unit, Orthopedic Surgery Department of San Cecilio University Hospital of Granada, and Department of Surgery, University of Granada, Granada, Spain.
Pedro
P
Hernández-Cortés
Hand Surgery Unit, Orthopedic Surgery Department of Virgen del Rocio University Hospital of Seville, Sevilla, Spain.
Miguel Angel
MA
Toledo-Romero
Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain.
Mario
M
Delgado
Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain.
Elena
E
Gonzalez-Rey
Hand Surgery Unit, Orthopedic Surgery Department of San Cecilio University Hospital of Granada, and Department of Surgery, University of Granada, Granada, Spain.
Rafael
R
Gómez Sánchez
Orthopedic Surgery Department of Virgen de las Nieves University Hospital of Granada, and Department of Surgery, University of Granada, Spain.
Nicolás
N
Prados-Olleta
Department of Pathology, School of Medicine, and Biopathology and Regenerative Medicine Institute (IBIMER), University of Granada, Granada, Spain.
José
J
Aneiros-Fernández
Department of Pathology, School of Medicine, and Biopathology and Regenerative Medicine Institute (IBIMER), University of Granada, Granada, Spain.
Vicente
V
Crespo-Lora
Department of Pathology, School of Medicine, and Biopathology and Regenerative Medicine Institute (IBIMER), University of Granada, Granaada, Spain.
Mariano
M
Aguilar
Oral Surgery and Implant Dentistry Department, School of Dentistry, University of Granada, Granada, Spain.
Pablo
P
Galindo-Moreno
Department of Pathology, School of Medicine, and Biopathology and Regenerative Medicine Institute (IBIMER), University of Granada, Granada, Spain. fovalle@ugr.es.
Francisco
F
O'Valle
D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D002208:Caproates; D004195:Disease Models, Animal; D054439:Ghrelin / Q000494:pharmacology*; D048091:Guided Tissue Regeneration / Q000379:methods*; D007783:Lactones; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D009416:Nerve Regeneration / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology
D002208:Caproates; D054439:Ghrelin; D007783:Lactones; C121056:caprolactone