Improved Efficacy of Delayed Treatment with Human Bone Marrow-Derived Stromal Cells Evaluated in Rats with Spinal Cord Injury

The treatment of spinal cord injury (SCI) with uncultivated human bone marrow-derived stromal cells (bmSCs) prepared by negative selection has been proposed to be therapeutically superior to treatment with stem cells that were expanded in vitro. To explore their use in clinical trials, we studied th...

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Main Authors: Marta Aguado-Garrido, Concepción García-Rama, Lorenzo Romero-Ramírez, Vinnitsa Buzoianu-Anguiano, Enrique Pérez-Rizo, Boris W. Kramer, Jörg Mey
Format: Article
Language:English
Published: MDPI AG 2024-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/25/3/1548
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author Marta Aguado-Garrido
Concepción García-Rama
Lorenzo Romero-Ramírez
Vinnitsa Buzoianu-Anguiano
Enrique Pérez-Rizo
Boris W. Kramer
Jörg Mey
author_facet Marta Aguado-Garrido
Concepción García-Rama
Lorenzo Romero-Ramírez
Vinnitsa Buzoianu-Anguiano
Enrique Pérez-Rizo
Boris W. Kramer
Jörg Mey
author_sort Marta Aguado-Garrido
collection DOAJ
description The treatment of spinal cord injury (SCI) with uncultivated human bone marrow-derived stromal cells (bmSCs) prepared by negative selection has been proposed to be therapeutically superior to treatment with stem cells that were expanded in vitro. To explore their use in clinical trials, we studied the functional effects of delayed application at 7 days after SCI by testing different doses of bmSCs. Spinal cord contusion injury was induced in adult male Wistar rats at the thoracic level T9. Human bmSCs were prepared by negative selection without expansion in vitro (NeuroCells<sup>TM</sup>). Treatment consisted of one 150 µL injection into the <i>cisterna magna</i> containing 0.5 or 2.5 million fresh bmSCs or 2.5 million bmSCs. The recovery of motor functions was evaluated during a surveillance period of six weeks (6 W), during which spinal cords were assessed histologically. Treatment resulted in a significant, dose-dependent therapeutic effect on the recovery of motor performance. The histological analysis revealed a lower degree of axonal degeneration and better survival of neurons and oligodendrocytes in bmSCs treated rats. Our results support delayed intrathecal application of bmSCs prepared by negative selection without expansion in vitro as a treatment of SCI.
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spelling doaj.art-6e5e0e02c7994527a5579ec659a5fcf42024-02-09T15:13:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-01253154810.3390/ijms25031548Improved Efficacy of Delayed Treatment with Human Bone Marrow-Derived Stromal Cells Evaluated in Rats with Spinal Cord InjuryMarta Aguado-Garrido0Concepción García-Rama1Lorenzo Romero-Ramírez2Vinnitsa Buzoianu-Anguiano3Enrique Pérez-Rizo4Boris W. Kramer5Jörg Mey6Hospital Nacional de Parapléjicos, 45071 Toledo, SpainHospital Nacional de Parapléjicos, 45071 Toledo, SpainHospital Nacional de Parapléjicos, 45071 Toledo, SpainHospital Nacional de Parapléjicos, 45071 Toledo, SpainHospital Nacional de Parapléjicos, 45071 Toledo, SpainNeuroplast BV, 6222 NK Maastricht, The NetherlandsHospital Nacional de Parapléjicos, 45071 Toledo, SpainThe treatment of spinal cord injury (SCI) with uncultivated human bone marrow-derived stromal cells (bmSCs) prepared by negative selection has been proposed to be therapeutically superior to treatment with stem cells that were expanded in vitro. To explore their use in clinical trials, we studied the functional effects of delayed application at 7 days after SCI by testing different doses of bmSCs. Spinal cord contusion injury was induced in adult male Wistar rats at the thoracic level T9. Human bmSCs were prepared by negative selection without expansion in vitro (NeuroCells<sup>TM</sup>). Treatment consisted of one 150 µL injection into the <i>cisterna magna</i> containing 0.5 or 2.5 million fresh bmSCs or 2.5 million bmSCs. The recovery of motor functions was evaluated during a surveillance period of six weeks (6 W), during which spinal cords were assessed histologically. Treatment resulted in a significant, dose-dependent therapeutic effect on the recovery of motor performance. The histological analysis revealed a lower degree of axonal degeneration and better survival of neurons and oligodendrocytes in bmSCs treated rats. Our results support delayed intrathecal application of bmSCs prepared by negative selection without expansion in vitro as a treatment of SCI.https://www.mdpi.com/1422-0067/25/3/1548spinal cord injurybone marrowstromal cellsneuroinflammationcytoprotection
spellingShingle Marta Aguado-Garrido
Concepción García-Rama
Lorenzo Romero-Ramírez
Vinnitsa Buzoianu-Anguiano
Enrique Pérez-Rizo
Boris W. Kramer
Jörg Mey
Improved Efficacy of Delayed Treatment with Human Bone Marrow-Derived Stromal Cells Evaluated in Rats with Spinal Cord Injury
International Journal of Molecular Sciences
spinal cord injury
bone marrow
stromal cells
neuroinflammation
cytoprotection
title Improved Efficacy of Delayed Treatment with Human Bone Marrow-Derived Stromal Cells Evaluated in Rats with Spinal Cord Injury
title_full Improved Efficacy of Delayed Treatment with Human Bone Marrow-Derived Stromal Cells Evaluated in Rats with Spinal Cord Injury
title_fullStr Improved Efficacy of Delayed Treatment with Human Bone Marrow-Derived Stromal Cells Evaluated in Rats with Spinal Cord Injury
title_full_unstemmed Improved Efficacy of Delayed Treatment with Human Bone Marrow-Derived Stromal Cells Evaluated in Rats with Spinal Cord Injury
title_short Improved Efficacy of Delayed Treatment with Human Bone Marrow-Derived Stromal Cells Evaluated in Rats with Spinal Cord Injury
title_sort improved efficacy of delayed treatment with human bone marrow derived stromal cells evaluated in rats with spinal cord injury
topic spinal cord injury
bone marrow
stromal cells
neuroinflammation
cytoprotection
url https://www.mdpi.com/1422-0067/25/3/1548
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