Failure of Schwann cells as supporting cells for adult neural progenitor cell grafts in the acutely injured spinal cord.
Adult neural progenitor cells (NPC) co-grafted with fibroblasts replace cystic lesion defects and promote cell-contact-mediated axonal regeneration in the acutely injured spinal cord. Fibroblasts are required as a platform to maintain NPC within the lesion; however, they are suspected to create an inhospitable milieu for regenerating central nervous system (CNS) axons. Therefore, we thought to replace fibroblasts by primary Schwann cells, which might serve as a superior scaffold to maintain NPC within the lesion and might further enhance axon regrowth and remyelination following spinal cord injury. Adult rats underwent a cervical dorsal column transection immediately followed by transplantation of either NPC/Schwann cell or NPC/Schwann cell/fibroblast co-grafts. Animals receiving Schwann cell or fibroblast grafts alone, or Schwann cell/fibroblast co-grafts served as controls. At 3 weeks after injury/transplantation, histological analysis revealed that only fibroblast-containing grafts were able to replace the cystic lesion defect. In both co-cultures and co-grafts, Schwann cells and NPC were segregated. Almost all NPC migrated out of the graft into the adjacent host spinal cord. As a consequence, only peripheral-type myelin, but no CNS-type myelin, was detected within co-grafts containing NPC/Schwann cells. Corticospinal axon regeneration into Schwann-cell-containing co-grafts was reduced. Taken together, Schwann cells within NPC grafts contribute to remyelination. However, Schwann cells fail as a supporting platform to maintain NPC within the graft and impair CNS axon regeneration; this makes them an unfavorable candidate to support/augment NPC grafts following spinal cord injury.
Vroemen
Maurice
M
Department of Neurology, University of Regensburg, Universitätsstrasse 84, 93053 Regensburg, Germany.
Caioni
Massimiliano
M
Bogdahn
Ulrich
U
Weidner
Norbert
N
D000818:Animals; D001369:Axons / Q000502:physiology; D002465:Cell Movement; D002470:Cell Survival; D018920:Coculture Techniques; D003560:Cysts / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D009186:Myelin Sheath / Q000378:metabolism / Q000502:physiology; D009416:Nerve Regeneration; D009474:Neurons; D051381:Rats; D011916:Rats, Inbred F344; D012583:Schwann Cells / Q000166:cytology* / Q000502:physiology / Q000637:transplantation*; D013119:Spinal Cord Injuries / Q000150:complications / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology