The Damaged Spinal Cord Is a Suitable Target for Stem Cell Transplantation
| Autor: | Kan Min, Reto Sutter, Rudolf P. Wüthrich, Armin Curt, Martin Schubert, Raphael Guzman, Dario Pfyffer, Steve Casha, Catherine R. Jutzeler, Evenline Huber, Markus Hupp, Susanne Friedl, Michael G. Fehlings, Jane Hsieh, Patrick Freund |
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| Přispěvatelé: | University of Zurich, Curt, Armin |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Oncology
Adult Male 030506 rehabilitation medicine.medical_specialty Cord medicine.medical_treatment Population 610 Medicine & health Thoracic Vertebrae 03 medical and health sciences Young Adult 0302 clinical medicine Neural Stem Cells Internal medicine medicine Humans 10035 Clinic for Nephrology education Spinal cord injury Spinal Cord Injuries education.field_of_study business.industry Process Assessment Health Care Immunosuppression General Medicine Middle Aged medicine.disease Spinal cord Transplantation 2742 Rehabilitation medicine.anatomical_structure 2728 Neurology (clinical) 2808 Neurology Feasibility Studies Female 10046 Balgrist University Hospital Swiss Spinal Cord Injury Center Stem cell 0305 other medical science business 030217 neurology & neurosurgery Adult stem cell Follow-Up Studies Stem Cell Transplantation |
| Popis: | Background. Given individuals with spinal cord injury (SCI) approaching 2 million, viable options for regenerative repair are desperately needed. Human central nervous system stem cells (HuCNS-SC) are self-renewing, multipotent adult stem cells that engraft, migrate, and differentiate in appropriate regions in multiple animal models of injured brain and spinal cord. Preclinical improved SCI locomotor function provided rationale for the first-in-human SCI clinical trial of HuCNS-SC cells. Evidence of feasibility and long-term safety of cell transplantation into damaged human cord is needed to foster translational progression of cellular therapies. Methods. A first-ever, multisite phase I/IIa trial involving surgical transplantation of 20 million HuCNS-SC cells into the thoracic cord in 12 AIS A or B subjects (traumatic, T2-T11 motor-complete, sensory-incomplete), aged 19 to 53 years, demonstrated safety and preliminary efficacy. Six-year follow-up data were collected (sensory thresholds and neuroimaging augmenting clinical assessments). Findings. The study revealed short- and long-term surgical and medical safety (well-tolerated immunosuppression in population susceptible to infections). Preliminary efficacy measures identified 5/12 with reliable sensory improvements. Unfortunately, without thoracic muscles available for manual muscle examination, thoracic motor changes could not be measured. Lower limb motor scores did not change during the study. Cervical cord imaging revealed, no tumor formation or malformation of the lesion area, and secondary supralesional structural changes similar to SCI control subjects. Interpretation. Short- and long-term safety and feasibility support the consideration of cell transplantation for patients with complete and incomplete SCI. This report is an important step to prepare, foster, and maintain the therapeutic development of cell transplantation for human SCI. |
| Databáze: | OpenAIRE |
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