Article - PathoPhysiology of Cell Injury Journal

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Bone-Marrow–Derived MSC Transplantation Enhances Neuronal Survival and Reduces Secondary Cellular Injury in Rat Spinal Cord Trauma Models

Aiden R. Halstrom PhD¹, Marissa K. Delaney PhD¹, Julian T. Kessler PhD^2*

¹Stem Cell and Molecular Therapeutics Division, Center for Advanced Translational Neuroscience, San Diego, California, USA.
²Laboratory of Neural Repair and Bioengineering, Atlantic Biomedical Sciences University, Boston, Massachusetts, USA.

DOI: 10.18081/pcij/2378-5225/14.18 Cited by 0 OpenAlex Scholar Crossref

Article history: Received 22 October 2024 · Revised 09 December 2024 · Accepted 19 December 2024 · Published 22 January 2025

Abstract

Background: Secondary cellular injury following spinal cord trauma contributes significantly to progressive neuronal loss, inflammation, oxidative stress, and functional decline. Bone-marrow–derived mesenchymal stem cells (BM-MSCs) have emerged as promising therapeutic candidates due to their potent immunomodulatory and neuroprotective properties. This study investigated the effects of BM-MSC transplantation on neuronal preservation, inflammatory signaling, apoptotic pathways, and functional recovery in a rat model of moderate contusion spinal cord injury (SCI).

Methods: Adult male Wistar rats were randomized into three groups: Sham, SCI + Vehicle, and SCI + MSC. A standardized T9–T10 contusion injury was induced using the NYU impactor. BM-MSCs (1×10⁶ cells) were administered intrathecally 24 h post-injury. Locomotor recovery was assessed using BBB scoring over 28 days. Histopathology (H&E, Nissl), immunohistochemistry (NeuN, GFAP, Iba-1, caspase-3, 8-OHdG), qRT-PCR, and Western blot were used to evaluate neuronal survival, glial activation, inflammation, apoptosis, and oxidative stress.

Results: MSC-treated rats demonstrated significantly improved BBB locomotor scores compared with vehicle controls (p < 0.01). Histological analyses revealed markedly smaller lesion cavities and greater preservation of white matter. Nissl staining showed increased neuronal survival (~70% vs. ~40%). MSC therapy significantly reduced TNF-α, IL-1β, IL-6, Bax, and cleaved caspase-3 expression, while up-regulating IL-10 and Bcl-2 (p < 0.01). Oxidative stress markers, including 8-OHdG, were also reduced. GFAP and Iba-1 staining indicated diminished astrocyte and microglial activation, reflecting attenuation of glial scar formation.

Conclusions: BM-MSC transplantation confers robust neuroprotection by suppressing inflammation, apoptosis, and oxidative injury, while promoting neuronal survival and functional recovery following SCI. These findings highlight the therapeutic potential of BM-MSCs in mitigating secondary injury mechanisms and support further exploration toward clinical translation in spinal cord trauma.

Keywords: Spinal cord injury; Mesenchymal stem cells; Bone-marrow–derived MSCs; Neuroprotection; Secondary injury

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BM-Publisher · Pathophysiology of Cell Injury Journal (PCIJ) · E-ISSN 2378-5225 · DOI Prefix 10.18081/2378-5225

Aiden R. Halstrom, M. K. D. J. T. K. (2025). . Pathophysiology of Cell Injury Journal (PCIJ), . https://pcij.net/archives/1671

Aiden R. Halstrom, Marissa K. Delaney, Julian T. Kessler. \".\" Pathophysiology of Cell Injury Journal (PCIJ), 2025, pp. . https://pcij.net/archives/1671

Aiden R. Halstrom, Marissa K. Delaney, Julian T. Kessler. . Pathophysiology of Cell Injury Journal (PCIJ). 2025;:. https://pcij.net/archives/1671

Aiden R. Halstrom, Marissa K. Delaney, Julian T. Kessler (2025) . Pathophysiology of Cell Injury Journal (PCIJ), , pp. . Available at: https://pcij.net/archives/1671

@article{aiden-r-halstrom-marissa-k-delaney-julian-t-kessler-2025, title = {}, author = {Aiden R. Halstrom, Marissa K. Delaney, Julian T. Kessler}, journal = {Pathophysiology of Cell Injury Journal (PCIJ)}, year = {2025}, url = {https://pcij.net/archives/1671}, }

TY - JOUR AU - Aiden R. Halstrom, Marissa K. Delaney, Julian T. Kessler TI - JO - Pathophysiology of Cell Injury Journal (PCIJ) PY - 2025 UR - https://pcij.net/archives/1671 ER -

Research Article
Article download: 48

Bone-Marrow–Derived MSC Transplantation Enhances Neuronal Survival and Reduces Secondary Cellular Injury in Rat Spinal Cord Trauma Models

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