Promoting survival, migration, and integration of transplanted Schwann cells by over-expressing polysialic acid.
The poor survival and migration of transplanted Schwann cells (SCs) are major drawbacks for their clinical application in cell therapy for neurotrauma. To overcome such drawbacks we genetically modified SCs to over-express polysialic acid (PSA) by lentiviral delivery of polysialyltransferase (PST) to study whether over-expression of PSA could enhance their survival, migration, and integration when transplanted into the spinal cord. It was found that more PSA-expressing SCs (PST/SCs) survived than GFP-expressing SCs (GFP/SCs) after transplantation, although cell loss was still quite significant. PSA expression did not enhance the motility of transplanted SCs in uninjured spinal cord. However, in a spinal cord crush injury model PST/SCs transplanted caudal to the lesion showed that increased number of PST/SCs migrated to the injury site compared with that of GFP/SCs. Induced expression of PSA in spinal cord can further facilitate the infiltration of PST/SCs into the lesion site. PST/SCs were also shown to intermingle well with host spinal cells while GFP/SCs formed boundaries with host tissue. This was confirmed by an in vitro confrontation assay showing that more PST/SCs crossed over to astrocyte territory than GFP/SCs. Furthermore, PST/SCs induced much less expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycan in the surrounding tissues than GFP/SCs, indicating that expression of PSA on SCs do not cause significant stress response of astrocytes. These results demonstrate that expression of PSA on SCs significantly changes their biological properties and makes them more feasible for neural repair after neurotrauma.
Centre for Neuroscience and Trauma, Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, Whitechapel, London E1 2AT, United Kingdom.
Juan
J
Luo
Xuenong
X
Bo
Dongsheng
D
Wu
John
J
Yeh
Peter M
PM
Richardson
Yi
Y
Zhang
D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000502:physiology*; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival / Q000502:physiology*; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D012794:Sialic Acids / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*
D012794:Sialic Acids; C021319:polysialic acid