Transplantation of autologous bone marrow-derived mononuclear cells into cerebrospinal fluid in a canine model of spinal cord injury

Regenerative Therapy(2023)

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摘要
Introduction: Spinal cord injury (SCI) is associated with severe dysfunction of nervous tissue, and repair via the transplantation of bone marrow-derived mononuclear cells (BM-MNCs) into cerebrospinal fluid yields promising results. It is essential to understand the underlying mechanisms; therefore, this study aimed to evaluate the regenerative potential of autologous BM-MNC transplantation in a canine model of acute SCI.Methods: Six dogs were included in this study, and SCI was induced using an epidural balloon catheter between L2 and L3, particularly in the area of the anterior longitudinal ligament. BM-MNC trans-plantation was performed, and T2-weighted magnetic resonance imaging (MRI) was conducted at specific time points (i.e., immediately after inducing SCI and at 1, 2, and 4 weeks after inducing SCI); moreover, the expression of growth-associated protein 43 (GAP-43) was evaluated.Results: MRI revealed that the signal intensity reduced over time in both BM-MNC-treated and control groups. However, the BM-MNC-treated group exhibited a significantly faster reduction than the control group during the early stages of SCI induction (BM-MNC-treated group: 4.82 +/- 0.135 cm [day 0], 1.71 +/- 0.134 cm [1 week], 1.37 +/- 0.036 cm [2 weeks], 1.21 cm [4 weeks]; control group: 4.96 +/- 0.211 cm [day 0], 2.49 +/- 0.570 cm [1 week], 1.56 +/- 0.045 cm [2 weeks], 1.32 cm [4 weeks]). During the early stages of treatment, GAP-43 was significantly expressed at the proximal end of the injured spinal cord in the BM-MSC-treated group, whereas it was scarcely expressed in the control group.Conclusions: In SCI, transplanted BM-MNCs can activate the expression of GAP-43, which is involved in axonal elongation (an important process in spinal cord regeneration). Thus, cell therapy with BM-MNCs can provide favorable outcomes in terms of better regenerative capabilities compared with other therapies.(c) 2023, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).
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关键词
Spinal cord injury,Bone marrow-derived mononuclear cells,Magnetic resonance imaging,Growth-associated protein 43,Canine model
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