Standardized human bone marrow-derived stem cells infusion improves survival and recovery in a rat model of spinal cord injury
Autor: | G. Brook, L. Jansen, O. Moskvin, Boris W. Kramer, S. Munter, Berta Cillero-Pastor, J. P. J. M. de Munter, J. Beugels, Tatyana Strekalova, D. A. Pavlov, Wolters E.Ch. |
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Přispěvatelé: | Promovendi MHN, Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, Promovendi NTM, Plastische Chirurgie (PLC), Ondersteunend personeel NTM, Imaging Mass Spectrometry (IMS), RS: M4I - Imaging Mass Spectrometry (IMS), Kindergeneeskunde, MUMC+: MA Medische Staf Kindergeneeskunde (9) |
Rok vydání: | 2019 |
Předmět: |
Male
Time Factors CYCLOSPORINE-A Interleukin-1beta CD34 LOCAL-DELIVERY Apoptosis Pharmacology 0302 clinical medicine 030212 general & internal medicine Gliosis Spinal cord injury Bone Marrow Transplantation Resolution of inflammation Astrogliosis medicine.anatomical_structure DIFFERENTIATION Neurology FUNCTIONAL RECOVERY medicine.symptom Stem cell Locomotion EXPRESSION Stromal cell Plasticity Inflammation Mesenchymal Stem Cell Transplantation 03 medical and health sciences Paracrine signalling Rats Nude medicine Regeneration Animals Humans Spinal Cord Injuries business.industry BLOOD-BRAIN-BARRIER Interleukin-6 Tumor Necrosis Factor-alpha EXTRACELLULAR VESICLES Recovery of Function Spinal cord medicine.disease APOPTOTIC CASCADE Rats STROMAL CELLS Neurology (clinical) business 030217 neurology & neurosurgery |
Zdroj: | Journal of the Neurological Sciences, 402, 16-29. Elsevier Science |
ISSN: | 1878-5883 0022-510X |
Popis: | Spinal cord injury (SCI) is an incurable disorder with an unmet need of an effective treatment. Recently, autologous human bone marrow-derived stem cells have shown to promote functional improvement, due to their anti-inflammatory and regenerative/apocrine properties. In this study, the primary objective was to test whether a single intrathecal injection with a 100 mu L suspension of 400,000 fresh human bone marrow-derived CD34(+) and an equal number of CMOS+ stem cells (Neuro-Cells (NC)), one day after balloon-compression of the spinal cord, improves motor function and reduces secondary damage in immunodeficient rats. During the first 5 weeks after this intervention, NC significantly improved locomotor recovery and induced less injury-associated adverse events compared to vehicle-treated rats.Histological analysis showed that NC reduced astrogliosis, and apoptosis early after administration (day 4), but not at a later stage (day 56) after SCI. Proteomic studies (at day 56) pointed to the release of paracrine factors and identified proteins involved in regenerative processes. As stem cells seem to reach their effects in acute lesions by mainly suppressing (secondary) inflammation, it is thus realistic to expect a lower magnitude of their eventual beneficial effect in T-cell deficient rats, a fact reinforcing the robustness of Neuro-Cells efficacy. Taken together, this study indicates that an intrathecal instillation of Neuro-Cells holds great promise as a neuroregenerative intervention in a clinical setting with acute SCI patients. |
Databáze: | OpenAIRE |
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