Transplantation of Human Neural Precursor Cells Reverses Syrinx Growth in a Rat Model of Post-Traumatic Syringomyelia.

Autor: Xu N; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.; Center for Reproductive Medicine, and Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Xu T; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.; Division of Neurogeriatrics, Karolinska Institutet, BioClinicum J10:30, Karolinska University Hospital, S17164, Solna, Sweden., Mirasol R; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.; National Institute of Neurological Disorders and Stroke, Stroke Branch, National Institutes of Health, Bethesda, MD, USA., Holmberg L; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden., Vincent PH; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden., Li X; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden., Falk A; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden., Benedikz E; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.; TEK-Innovation, Faculty of Engineering, University of Southern Denmark, DK-5000, Odense, Denmark., Rotstein E; Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, S-14186, Stockholm, Sweden., Seiger Å; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden., Åkesson E; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.; Stockholms Sjukhem Foundation, Box 12230, S-10226, Stockholm, Sweden., Falci S; Department of Neurosurgery, Craig Hospital, 3425 S. Clarkson St, Englewood, CO, 80110, USA., Sundström E; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. erik.sundstrom@ki.se.; Division of Neurogeriatrics, Karolinska Institutet, BioClinicum J9:20, Karolinska University Hospital, S17164, Solna, Sweden. erik.sundstrom@ki.se.
Jazyk: angličtina
Zdroj: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics [Neurotherapeutics] 2021 Apr; Vol. 18 (2), pp. 1257-1272. Date of Electronic Publication: 2021 Jan 19.
DOI: 10.1007/s13311-020-00987-3
Abstrakt: Posttraumatic syringomyelia (PTS) is a serious condition of progressive expansion of spinal cord cysts, affecting patients with spinal cord injury years after injury. To evaluate neural cell therapy to prevent cyst expansion and potentially replace lost neurons, we developed a rat model of PTS. We combined contusive trauma with subarachnoid injections of blood, causing tethering of the spinal cord to the surrounding vertebrae, resulting in chronically expanding cysts. The cysts were usually located rostral to the injury, extracanalicular, lined by astrocytes. T2*-weighted magnetic resonance imaging (MRI) showed hyperintense fluid-filled cysts but also hypointense signals from debris and iron-laden macrophages/microglia. Two types of human neural stem/progenitor cells-fetal neural precursor cells (hNPCs) and neuroepithelial-like stem cells (hNESCs) derived from induced pluripotent stem cells-were transplanted to PTS cysts. Cells transplanted into cysts 10 weeks after injury survived at least 10 weeks, migrated into the surrounding parenchyma, but did not differentiate during this period. The cysts were partially obliterated by the cells, and cyst walls often merged with thin layers of cells in between. Cyst volume measurements with MRI showed that the volumes continued to expand in sham-transplanted rats by 102%, while the cyst expansion was effectively prevented by hNPCs and hNESCs transplantation, reducing the cyst volumes by 18.8% and 46.8%, respectively. The volume reductions far exceeded the volume of the added human cells. Thus, in an animal model closely mimicking the clinical situation, we provide proof-of-principle that transplantation of human neural stem/progenitor cells can be used as treatment for PTS.
(© 2021. The Author(s).)
Databáze: MEDLINE
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