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Stem Cell Therapy in Spinal Cord Injury: In Vivo and Postmortem Tracking of Bone Marrow Mononuclear or Mesenchymal Stem Cells

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Abstract

Objective

The aim of this study was to address the question of whether bone marrow-originated mononuclear cells (MNC) or mesenchymal stem cells (MSC) induce neural regeneration when implanted intraspinally.

Materials and Methods

The study design included 4 groups of mice: Group 1, non-traumatized control group; Groups 2, 3 and 4 spinal cord traumatized mice with 1 g force Tator clips, which received intralesionally either no cellular implants (Group 2), luciferase (Luc) (+) MNC (Group 3) or MSC (Group 4) obtained from CMV-Luc or beta-actin Luc donor transgenic mice. Following the surgery until decapitation, periodical radioluminescence imaging (RLI) and Basso Mouse Scale (BMS) evaluations was performed to monitor neural activity. Postmortem immunohistochemical techniques were used to analyze the fate of donor type implanted cells.

Results

All mice of Groups 3 and 4 showed various degrees of improvement in the BMS scores, whereas there was no change in Groups 1 and 2. The functional improvement was significantly better in Group 4 compared to Group 3 (18 vs 8, p = 0.002). The immunohistochemical staining demonstrated GFP+Luc+ neuronal/glial cells that were also positive with one or more of these markers: nestin, myelin associated glycoprotein, microtubule associated protein or myelin oligodendrocyte specific protein, which is considered as indicator of donor type neuronal regeneration. Frequency of donor type neuronal cells; Luc + signals and median BMS scores were observed 48–64 % and 68–72 %; 44–80 %; 8 and 18 within Groups III and IV respectively.

Discussion

MSCs were more effective than MNC in obtaining neuronal recovery. Substantial but incomplete functional improvement was associated with donor type in vivo imaging signals more frequently than the number of neuronal cells expressing donor markers in spinal cord sections in vitro. Our results are in favor of functional recovery arising from both donor MSC and MNCs, contributing to direct neuronal regeneration and additional indirect mechanisms.

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Acknowledgment

This study was supported by grants from the Turkish Scientific Research Council TUBİTAK, Ankara University Research Resources (SBAG) and the Turkish Academy of Sciences.

Conflicts of Interest

The authors declare no potential conflicts of interest.

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Authors and Affiliations

  1. School of Medicine, Department of Neurosurgery, Pamukkale University, 20070, Kinikli, Denizli, Turkey

    Mevci Ozdemir

  2. School of Medicine, Department of Neurosurgery, Ankara University, Ankara, Turkey

    Ayhan Attar & Melih Bozkurt

  3. School of Medicine, Department of Pathology, Ankara University, Ankara, Turkey

    Isinsu Kuzu

  4. Neurosurgery Clinic, Ankara Guven Hospital, Ankara, Turkey

    Murat Ayten

  5. School of Medicine, Department of Anesthesiology, Ankara University, Ankara, Turkey

    Enver Ozgencil

  6. School of Medicine, Department of Heamatology, Ankara University, Cebeci yerleşkesi, Dikimevi, 06620, Ankara, Turkey

    Klara Dalva & Meral Beksac

  7. School of Medicine, Department of Pediatric Hematology, Hacettepe University, Ankara, Turkey

    Duygu Uckan & Emine Kılıc

  8. School of Medicine, Department of Radiology, Ufuk University, Ankara, Turkey

    Tanzer Sancak

  9. School of Medicine, Department of Neurosurgery, President, The Turkish Academi of Sciences, Emeritus, Ankara University, Ankara, Turkey

    Yucel Kanpolat

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  1. Mevci Ozdemir
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Correspondence to Mevci Ozdemir or Meral Beksac.

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Ozdemir, M., Attar, A., Kuzu, I. et al. Stem Cell Therapy in Spinal Cord Injury: In Vivo and Postmortem Tracking of Bone Marrow Mononuclear or Mesenchymal Stem Cells. Stem Cell Rev and Rep 8, 953–962 (2012). https://doi.org/10.1007/s12015-012-9376-5

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  • DOI: https://doi.org/10.1007/s12015-012-9376-5

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