Standardized human bone marrow-derived stem cells infusion improves survival and recovery in a rat model of spinal cord injury

J. P. de Munter, J. Beugels, S. Munter, L. Jansen, B. Cillero-Pastor, O. Moskvin, G. Brook, D. Pavlov, T. Strekalova, B. W. Kramer*, E. Ch Wolters

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Pages (from-to)16-29
Number of pages14
JournalJournal of the Neurological Sciences
Volume402
DOIs
Publication statusPublished - 15 Jul 2019

Keywords

  • Plasticity
  • Regeneration
  • Inflammation
  • Resolution of inflammation
  • BLOOD-BRAIN-BARRIER
  • EXTRACELLULAR VESICLES
  • FUNCTIONAL RECOVERY
  • APOPTOTIC CASCADE
  • LOCAL-DELIVERY
  • CYCLOSPORINE-A
  • STROMAL CELLS
  • DIFFERENTIATION
  • INFLAMMATION
  • EXPRESSION

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