Bone marrow stromal cells and resorbable collagen guidance tubes enhance sciatic nerve regeneration in mice.
We evaluated peripheral nerve regeneration using a tubular nerve guide of resorbable collagen filled with either bone marrow-derived cells (BMDCs) in Dulbecco's cell culture medium (DMEM) or with DMEM alone (control). The control group received just the culture medium (vehicle). The left sciatic nerves of ten isogenic mice were transected and the tubular nerve guides were sutured to the end of the proximal and distal nerve stumps. Motor function was tested at 2, 4 and 6 weeks after surgery using the walking track test. The pawprints were analyzed and the print lengths (PL) were measured to evaluate functional recovery. After 6 weeks, mice were anesthetized, perfused transcardially with fixative containing aldehydes, and the sciatic nerves and tubes were dissected and processed for scanning and transmission electron microscopy. Scanning electron microscopy of the collagen tube revealed that the tube wall became progressively thinner after surgery, proving that the tube can be resorbed in vivo. Quantitative analysis of the regenerating nerves showed that the number of myelinated fibers and the myelin area were significantly increased in the experimental group. Also, motor function recovery was faster in animals that received the cell grafts. These results indicate that the collagen tube filled with BMDCs provided an adequate and favorable environment for the growth and myelination of regenerating axons compared to the collagen tube alone.
Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Brasil.
Fátima Rosalina
FR
Pereira Lopes
Lenira
L
Camargo de Moura Campos
José
J
Dias Corrêa
Alex
A
Balduino
Silvano
S
Lora
Francesco
F
Langone
Radovan
R
Borojevic
Ana Maria
AM
Blanco Martinez
D000818:Animals; D001672:Biocompatible Materials / Q000627:therapeutic use; D015152:Blotting, Northern / Q000379:methods; D001854:Bone Marrow Cells / Q000502:physiology* / Q000648:ultrastructure; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron / Q000379:methods; D009043:Motor Activity / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012584:Sciatic Nerve / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D020426:Sciatic Neuropathy / Q000473:pathology / Q000601:surgery*; D017154:Stromal Cells / Q000502:physiology / Q000648:ultrastructure; D013997:Time Factors
D001672:Biocompatible Materials; D012333:RNA, Messenger; D003094:Collagen