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Transplants of Human Mesenchymal Stem Cells Improve Functional Recovery After Spinal Cord Injury in the Rat

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Human mesenchymal stem cells (hMSCs) derived from adult bone marrow represent a potentially useful source of cells for cell replacement therapy after nervous tissue damage. They can be expanded in culture and reintroduced into patients as autografts or allografts with unique immunologic properties. The aim of the present study was to investigate (i) survival, migration, differentiation properties of hMSCs transplanted into non-immunosuppressed rats after spinal cord injury (SCI) and (ii) impact of hMSC transplantation on functional recovery. Seven days after SCI, rats received i.v. injection of hMSCs (2×106 in 0.5 mL DMEM) isolated from adult healthy donors. Functional recovery was assessed by Basso–Beattie–Bresnahan (BBB) score weekly for 28 days. Our results showed gradual improvement of locomotor function in transplanted rats with statistically significant differences at 21 and 28 days. Immunocytochemical analysis using human nuclei (NUMA) and BrdU antibodies confirmed survival and migration of hMSCs into the injury site. Transplanted cells were found to infiltrate mainly into the ventrolateral white matter tracts, spreading also to adjacent segments located rostro-caudaly to the injury epicenter. In double-stained preparations, hMSCs were found to differentiate into oligodendrocytes (APC), but not into cells expressing neuronal markers (NeuN). Accumulation of GAP-43 regrowing axons within damaged white matter tracts after transplantation was observed. Our findings indicate that hMSCs may facilitate recovery from spinal cord injury by remyelinating spared white matter tracts and/or by enhancing axonal growth. In addition, low immunogenicity of hMSCs was confirmed by survival of donor cells without immunosuppressive treatment.

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ACKNOWLEDGMENTS

This work was supported by APVV 51-002105, VEGA 2/5136/25, STAA 51-011-604. We express our thanks to Marika Špontáková for her great assistance in the immunocytochemical analysis as well as to Monika Ragáliová and Ivana Kupsáková for their helpful advice in cell culture preparation.

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Authors and Affiliations

  1. Institute of Neurobiology, Center of Excellence, SAS, Šoltésovej 4, Košice, 04001, Slovakia

    Daša Čížková, Ivo Vanický & Stanislava Jergová

  2. Associated Tissue Bank, Faculty of Medicine and University Hospital, P.J. Šafárik University, Trieda SNP 1, Košice, 04011, Slovakia

    Ján Rosocha

  3. UVM, Komenského 72, Košice, Slovakia

    Milan Čížek

  4. Institute of Neurobiology, Center of Excellence, SAS, Šoltésovej 4, Košice, 04001, Slovakia

    Daša Čížková

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  1. Daša Čížková
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Correspondence to Daša Čížková.

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Čížková, D., Rosocha, J., Vanický, I. et al. Transplants of Human Mesenchymal Stem Cells Improve Functional Recovery After Spinal Cord Injury in the Rat. Cell Mol Neurobiol 26, 1165–1178 (2006). https://doi.org/10.1007/s10571-006-9093-1

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