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Research ArticleLumbar

Intradiscal Injection of Iron-Labeled Autologous Mesenchymal Stromal Cells in Patients With Chronic Low Back Pain: A Feasibility Study With 2 Years Follow-Up

Nikolaos Papadimitriou, Hanna Hebelka, Daphne Hingert, Adad Baranto, Helena Barreto Henriksson, Anders Lindahl and Helena Brisby
International Journal of Spine Surgery December 2021, 15 (6) 1201-1209; DOI: https://doi.org/10.14444/8152
Nikolaos Papadimitriou
1 Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
2 Department of Orthopaedics, Sahgrenska University Hospital, Gothenburg, Sweden
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Hanna Hebelka
1 Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
3 Department of Radiology, Sahlgrenska University Hospital, Gothenburg, Sweden
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Daphne Hingert
1 Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Adad Baranto
1 Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
2 Department of Orthopaedics, Sahgrenska University Hospital, Gothenburg, Sweden
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Helena Barreto Henriksson
1 Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
4 Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
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Anders Lindahl
5 Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy University of Gothenburg, Gothenburg, Sweden
6 Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden
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Helena Brisby
1 Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
2 Department of Orthopaedics, Sahgrenska University Hospital, Gothenburg, Sweden
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    Figure 1

    Representative images from baseline T2-weighted MRI controls from 2 patients. The L4-L5 intervertebral disc was addressed in both. To the left (A1, A3, B1, and B3) midsagittal images. The blue lines represent the level of the axial images shown to the right (A2, A4, B2, and B4). On the upper row (A2 and B2) the foramina can be evaluated, and on the lower row, the facet joints can be seen (indicated unilaterally by ellipses in orange).

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    Figure 2

    Bone marrow–derived mesenchymal stromal cells (BM-MSCs) in culture. Cells from the same patient at different time points. (A) BM-MSCs after 6 days of culture. (B) BM-MSCs after 12 days of culture. (C) BM-MSCs prior to iron labeling. (D) Cells just prior to injection.

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    Figure 3

    Representative images of histological sections of bone marrow–derived mesenchymal stromal cells pellets harvested at day 28, stained with Alcian blue Van Gieson. (A) Pellet from iron-labeled cells. (B) Pellet from nonlabeled cells. The blue color represents proteoglycans and black dots signify cell nuclei. As can be observed, proteoglycan accumulation is more evident in the nonlabeled cells.

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    Figure 4

    Magnetic resonance imaging examinations of the same patient throughout the duration of the study (mo = months). Midsagittal sections, T2W images on top row, T1W on bottom. The 3 distal lumbar and the first sacral vertebrae are marked (L3-5 and S1). Injection of mesenchymal stromal cells was performed at the L4-L5 level (encircled). Routine evaluation revealed no evident morphological changes.

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    Figure 5

    Diagrams depicting results for (A) European quality of life-5 dimensions index. (B) Numerical Rating Scale for back pain. (C) Oswestry Disability Index for all patients over time. Patients 2, 3, and 5 opted for surgery within 1 year, patient 6 within 2 years, and patient 4 within 3 years.

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    Table 1

    Fluorescence-activated cell sorting analysis of the cell isolate after bone marrow aspiration and of the cell population for implantation.

     Surface MarkersIsolation
    % of Cells, Mean (SD)
    Implantation
    % of Cells, Mean (SD)
    Surface Markers Used for Hematopoietic Lineage Characterization
     CD 34+/CD 45−1.8 (1.7)0.6 (0.5)
     CD 45+/CD 34−42.8 (13.1)0.4 (0.3)
     CD34+/CD45+0.7 (0.8)0.1 (0.1)
    Surface Markers Used for MSC Lineage Characterization
     CD 105+/CD 166−1.6 (2.3)5.0 (8.7)
     CD 166+/CD 105−0.2 (0.4)0.3 (0.4)
     CD105+/CD 166+0.9 (2.2)58.8 (16.4)
     CD 90+0.4 (0.5)71.3 (12.8)
     CD 90+ of CD105+/CD166+ND a 98.1 (1.1)
    • aThere were very few observations of CD90+ cells among the CD105+/CD166+ cells directly after isolation, thus a mean value could not be calculated.

    • MSC, mesenchymal stromal cells.

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    Table 2

    Results of patient-reported outcome measures at different time points, presented as mean value and 95% confidence interval.

    PROMsPreop (n = 9)3 mo (n = 7)6 mo (n = 6)12 mo (n = 6)24 mo (n = 5)
    NRS back pain (0–10)7.4 (6.3–8.6)6.4 (3.9–8.9)6.1 (4.3–7.9)4.3 (0.7–8.0)4.6 (1.7–7.5)
    NRS leg pain (0–10)4.9 (2.6–7.2)4.9 (1.6–8.1)4.2 (1.7–6.7)2.2 (1.9–6.2)2.6 (1.9–7.1)
    EQ-5D index (0–1.0)0.43 (0.25–0.61)0.48 (0.21–0.75)0.53 (0.30–0.76)0.62 (0.27–0.98)0.68 (0.34–1.00)
    ODI (0–100)40 (39–59)41 (16–67)39 (22–57)30 (8–68)22 (0–45)
    • EQ-5D, European quality of life-5 dimensions; NRS, numerical rating scale; ODI, oswestry disability index; PROMs, patient-reported outcome measures.

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International Journal of Spine Surgery
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1 Dec 2021
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Intradiscal Injection of Iron-Labeled Autologous Mesenchymal Stromal Cells in Patients With Chronic Low Back Pain: A Feasibility Study With 2 Years Follow-Up
Nikolaos Papadimitriou, Hanna Hebelka, Daphne Hingert, Adad Baranto, Helena Barreto Henriksson, Anders Lindahl, Helena Brisby
International Journal of Spine Surgery Dec 2021, 15 (6) 1201-1209; DOI: 10.14444/8152

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Intradiscal Injection of Iron-Labeled Autologous Mesenchymal Stromal Cells in Patients With Chronic Low Back Pain: A Feasibility Study With 2 Years Follow-Up
Nikolaos Papadimitriou, Hanna Hebelka, Daphne Hingert, Adad Baranto, Helena Barreto Henriksson, Anders Lindahl, Helena Brisby
International Journal of Spine Surgery Dec 2021, 15 (6) 1201-1209; DOI: 10.14444/8152
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Keywords

  • disc degeneration
  • low back pain
  • mesenchymal stromal cell
  • cell therapy
  • cell labeling

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