Schwann cells generated from neonatal skin-derived precursors or neonatal peripheral nerve improve functional recovery after acute transplantation into the partially injured cervical spinal cord of the rat.
The transplantation of Schwann cells (SCs) holds considerable promise as a therapy for spinal cord injury, but the optimal source of these cells and the best timing for intervention remains debatable. Previously, we demonstrated that delayed transplantation of SCs generated from neonatal mouse skin-derived precursors (SKP-SCs) promoted repair and functional recovery in rats with thoracic contusions. Here, we conducted two experiments using neonatal rat cells and an incomplete cervical injury model to examine the efficacy of acute SKP-SC transplantation versus media control (Experiment 1) and versus nerve-derived SC or dermal fibroblast (Fibro) transplantation (Experiment 2). Despite limited graft survival, by 10 weeks after injury, rats that received SCs from either source showed improved functional recovery compared with media- or fibroblast-treated animals. Compared with media treatment, SKP-SC-transplanted rats showed enhanced rubrospinal tract (RST) sparing/plasticity in the gray matter (GM) rostral to injury, particularly in the absence of immunosuppression. The functional benefits of SC transplantations over fibroblast treatment correlated with the enhanced preservation of host tissue, reduced RST atrophy, and/or increased RST sparing/plasticity in the GM. In summary, our results indicate that: (1) early transplantation of neonatal SCs generated from skin or nerve promotes repair and functional recovery after incomplete cervical crush injury; (2) either of these cell types is preferable to Fibros for these purposes; and (3) age-matched SCs from these two sources do not differ in terms of their reparative effects or functional efficacy after transplantation into the injured cervical spinal cord.
International Collaboration on Repair Discoveries and.
Joseph S
http://orcid.org/0000-0001-8004-0958
JS
Sparling
International Collaboration on Repair Discoveries and.
Frederic
F
Bretzner
Developmental and Stem Cell Biology Group and.
Jeff
J
Biernaskie
International Collaboration on Repair Discoveries and.
Peggy
P
Assinck
International Collaboration on Repair Discoveries and.
Yuan
Y
Jiang
International Collaboration on Repair Discoveries and.
Hiroki
H
Arisato
International Collaboration on Repair Discoveries and.
Ward T
WT
Plunet
International Collaboration on Repair Discoveries and.
Jaimie
J
Borisoff
International Collaboration on Repair Discoveries and.
Jie
J
Liu
Developmental and Stem Cell Biology Group and Neurosciences and Mental Health, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada M5G 1L7.
Freda D
FD
Miller
International Collaboration on Repair Discoveries and Departments of Zoology and Surgery, University of British Columbia, Vancouver, British Columbia, Canada V5Z 1M9, and tetzlaff@icord.org.
Wolfram
W
Tetzlaff
D000818:Animals; D000831:Animals, Newborn; D001710:Biotin / Q000031:analogs & derivatives; D002454:Cell Differentiation; D002478:Cells, Cultured; D066193:Cervical Cord; D003911:Dextrans; D004195:Disease Models, Animal; D005552:Forelimb / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010525:Peripheral Nerves / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D020127:Recovery of Function / Q000502:physiology*; D012583:Schwann Cells / Q000502:physiology / Q000637:transplantation*; D012867:Skin / Q000166:cytology*; D013119:Spinal Cord Injuries / Q000601:surgery*; D017154:Stromal Cells / Q000502:physiology
D003911:Dextrans; D009419:Nerve Tissue Proteins; C076397:biotinylated dextran amine; D049452:Green Fluorescent Proteins; D001710:Biotin
Schwann cells; cyclosporine A; forelimb behavior; skin-derived precusors; spinal cord injury; transplantation