title: Neuroprotective effects of human spinal cord-derived neural precursor cells after transplantation to the injured spinal cord.
abstract: To validate human neural precursor cells (NPCs) as potential donor cells for transplantation therapy after spinal cord injury (SCI), we investigated the effect of NPCs, transplanted as neurospheres, in two different rat SCI models. Human spinal cord-derived NPCs (SC-NPCs) transplanted 9 days after spinal contusion injury enhanced hindlimb recovery, assessed by the BBB locomotor test. In spinal compression injuries, SC-NPCs transplanted immediately or after 1 week, but not 7 weeks after injury, significantly improved hindlimb recovery compared to controls. We could not detect signs of mechanical allodynia in transplanted rats. Four months after transplantation, we found more human cells in the host spinal cord than were transplanted, irrespective of the time of transplantation. There was no focal tumor growth. In all groups the vast majority of NPCs differentiated into astrocytes. Importantly, the number of surviving rat spinal cord neurons was highest in groups transplanted acutely and subacutely, which also showed the best hindlimb function. This suggests that transplanted SC-NPCs improve the functional outcome by a neuroprotective effect. We conclude that SC-NPCs reliably enhance the functional outcome after SCI if transplanted acutely or subacutely, without causing allodynia. This therapeutic effect is mainly the consequence of a neuroprotective effect of the SC-NPCs.
authors.affiliation: Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Geriatric Clinic Res Lab., Novum, S-14186 Stockholm, Sweden.
authors.forename: Mia
authors.initials: M
authors.lastname: Emgård
authors.affiliation: Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Geriatric Clinic Res Lab., Novum, S-14186 Stockholm, Sweden.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Piao
authors.affiliation: Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Geriatric Clinic Res Lab., Novum, S-14186 Stockholm, Sweden; Stockholms Sjukhem Foundation, Mariebergsgatan 22, S-11235 Stockholm, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Aineskog
authors.affiliation: Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Geriatric Clinic Res Lab., Novum, S-14186 Stockholm, Sweden.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Geriatric Clinic Res Lab., Novum, S-14186 Stockholm, Sweden.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Calzarossa
authors.affiliation: Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Geriatric Clinic Res Lab., Novum, S-14186 Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Odeberg
authors.affiliation: Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Geriatric Clinic Res Lab., Novum, S-14186 Stockholm, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Holmberg
authors.affiliation: Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Geriatric Clinic Res Lab., Novum, S-14186 Stockholm, Sweden.
authors.forename: Eva-Britt
authors.initials: EB
authors.lastname: Samuelsson
authors.affiliation: Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, S-14186 Stockholm, Sweden.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Bezubik
authors.affiliation: Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Geriatric Clinic Res Lab., Novum, S-14186 Stockholm, Sweden.
authors.forename: Per Henrik
authors.initials: PH
authors.lastname: Vincent
authors.affiliation: Department of Neurosurgery, Craig Hospital, 3425 S. Clarkson St., Englewood, CO 80110, USA.
authors.forename: Scott P
authors.initials: SP
authors.lastname: Falci
authors.affiliation: Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Geriatric Clinic Res Lab., Novum, S-14186 Stockholm, Sweden; Stockholms Sjukhem Foundation, Mariebergsgatan 22, S-11235 Stockholm, Sweden.
authors.forename: Åke
authors.initials: Å
authors.lastname: Seiger
authors.affiliation: Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Geriatric Clinic Res Lab., Novum, S-14186 Stockholm, Sweden; Stockholms Sjukhem Foundation, Mariebergsgatan 22, S-11235 Stockholm, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Åkesson
authors.affiliation: Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Geriatric Clinic Res Lab., Novum, S-14186 Stockholm, Sweden; Stockholms Sjukhem Foundation, Mariebergsgatan 22, S-11235 Stockholm, Sweden. Electronic address: erik.sundstrom@ki.se.
authors.forename: Erik
authors.initials: E
authors.lastname: Sundström
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus; D005786:Gene Expression Regulation / Q000502:physiology; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006614:Hindlimb / Q000503:physiopathology; D006801:Humans; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology* / Q000637:transplantation*; D017288:Pain Threshold / Q000502:physiology; D051381:Rats; D013116:Spinal Cord / Q000166:cytology*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors
chemical_list: D055551:HSP27 Heat-Shock Proteins; D009419:Nerve Tissue Proteins
keywords: Motor function; Neural precursor cells; Neuroprotection; Spinal cord injury; Transplantation