Zamanian Cameron, Onyedimma Chiduziem, Moinuddin F M, Ghaith Abdul Karim, Jarrah Ryan, Dhar Ashis, Windebank Anthony J, Bydon Mohamad
Mayo Clinic Neuro-Informatics Laboratory, Mayo Clinic, Rochester, Minnesota, USA.
Department of Neurological Surgery, Mayo Clinic, Rochester, Minnesota, USA.
J Spinal Cord Med. 2025 May;48(3):527-535. doi: 10.1080/10790268.2023.2274637. Epub 2023 Nov 20.
Exosomes represent extracellular vesicles that mediate intercellular interactions and have been extensively studied for their therapeutic potential. Purified exosomes product (PEP) from human plasma is reported to aid in tissue repair but has never been evaluated as a potential therapy for spinal cord injury (SCI).
We aim to investigate the effects of PEP on axon myelination, reduction in cavity size, and functional improvements in rats following SCI.
Following T9-T10 laminectomy and contusion to the spinal cord, female rats received either intrathecal (IT) PEP, IT ringer-lactate solution (RL), intravenous (IV) PEP, or IV RL one day post injury. Rats underwent behavioral assessments each week for 10 weeks following SCI. After 10 weeks, histological evaluations were performed to quantity axon myelination and cavity size.
The IT PEP group had significantly (P ≤ 0.05) more myelinated axons 1000 μm rostral to the injury, at the epicenter, and 1000 μm caudal of the injury (34.3 ± 3.1, 27.7 ± 2.1, and 32.0 ± 1.7, respectively) compared to the IT RL group (27.3 ± 2.5, 17.3 ± 2.5, and 23.3 ± 2.5, respectively). In addition, IT PEP rats had significantly reduced cavity size at the injury epicenter compared to controls (28.31%±1.74% vs. 34.39%±3.78%, respectively). Lastly, functional improvements were observed and sustained beginning at the 31 days following injury. The IV PEP group did not show sustained functional improvement compared to the IV RL rats.
Our results suggest that IT PEP injection may yield beneficial effects following SCI. However, further studies are warranted to investigate the role of PEP following SCI and to optimize its potential for clinical translation.
外泌体是介导细胞间相互作用的细胞外囊泡，其治疗潜力已得到广泛研究。据报道，从人血浆中纯化的外泌体产物（PEP）有助于组织修复，但从未被评估为脊髓损伤（SCI）的潜在治疗方法。
我们旨在研究PEP对SCI后大鼠轴突髓鞘形成、空洞大小减小和功能改善的影响。
在T9-T10椎板切除术和脊髓挫伤后，雌性大鼠在损伤后一天接受鞘内（IT）PEP、IT乳酸林格液（RL）、静脉内（IV）PEP或IV RL治疗。SCI后10周内，每周对大鼠进行行为评估。10周后，进行组织学评估以量化轴突髓鞘形成和空洞大小。
与IT RL组（分别为27.3±2.5、17.3±2.5和23.3±2.5）相比，IT PEP组在损伤部位上方1000μm、损伤中心和损伤部位下方1000μm处有明显更多的有髓轴突（分别为34.3±3.1、27.7±2.1和32.0±1.7）。此外，与对照组相比，IT PEP大鼠损伤中心的空洞大小明显减小（分别为28.31%±1.74%和34.39%±3.78%）。最后，在损伤后31天开始观察到功能改善并持续存在。与IV RL大鼠相比，IV PEP组未显示出持续的功能改善。
我们的结果表明，SCI后注射IT PEP可能产生有益效果。然而，有必要进一步研究PEP在SCI后的作用，并优化其临床转化潜力。
