White Seok Voon, Ma Yee Hang Ethan, Plant Christine D, Harvey Alan R, Plant Giles W
Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
School of Human Sciences, University of Western Australia, Crawley, WA 6009, Australia.
Cells. 2025 Apr 23;14(9):630. doi: 10.3390/cells14090630.
Mesenchymal progenitor cells (MPC) are effective in reducing tissue loss, preserving white matter, and improving forelimb function after a spinal cord injury (SCI). We proposed that by preconditioning the mouse by the intravenous delivery (IV) of MPCs for 24 h following SCI, this would provide a more favorable tissue milieu for an NSC intraspinal bridging transplantation at day three and day seven. In combination, these transplants will provide better anatomical and functional outcomes. The intravenous MSCs would provide cell protection and reduce inflammation. NSCs would provide a tissue bridge for axonal regeneration and myelination and reconnect long tract spinal pathways. Results showed that initial protection of the injury site by IV MPCs transplantation resulted in no increased survival of the NSCs transplanted at day seven. However, integration of transplanted NSCs was increased at the day three timepoint, indicating MPCs influence very early immune signaling. We show, in this study, that MPC transplantation resulted in a co-operative NSC cell survival improvement on day three post-SCI. In addition to increased NSC survival on day three, there was an increase in NSC-derived mature oligodendrocytes at this early timepoint. An in vitro analysis confirmed MPC-driven oligodendrocyte differentiation, which was statistically increased when compared to control NSC-only cultures. These observations provide important information about the combination, delivery, and timing of two cellular therapies in treating SCI. This study provides important new data on understanding the MPC inflammatory signaling within the host tissue and timepoints for cellular transplantation survival and oligodendroglia differentiation. These results demonstrate that MPC transplantation can alter the therapeutic window for intraspinal transplantation by controlling both the circulating inflammatory response and local tissue milieu.
间充质祖细胞（MPC）在减少脊髓损伤（SCI）后的组织损失、保留白质和改善前肢功能方面具有显著效果。我们提出，在脊髓损伤后通过静脉注射（IV）MPC对小鼠进行24小时预处理，这将为在第三天和第七天进行的神经干细胞（NSC）脊髓内桥接移植提供更有利的组织环境。综合起来，这些移植将带来更好的解剖学和功能结果。静脉注射的间充质干细胞（MSCs）将提供细胞保护并减轻炎症。神经干细胞将为轴突再生和髓鞘形成提供组织桥，并重新连接脊髓长束通路。结果表明，通过静脉注射MPC移植对损伤部位的初始保护并未导致在第七天移植的神经干细胞存活率增加。然而，在第三天时间点，移植的神经干细胞的整合增加，表明MPC对早期免疫信号有影响。在本研究中，我们表明MPC移植在脊髓损伤后第三天协同提高了神经干细胞的存活率。除了第三天神经干细胞存活率增加外，在这个早期时间点神经干细胞来源的成熟少突胶质细胞也有所增加。体外分析证实了MPC驱动的少突胶质细胞分化，与仅培养对照神经干细胞相比，其在统计学上有显著增加。这些观察结果为两种细胞疗法在治疗脊髓损伤中的联合、递送和时机提供了重要信息。本研究提供了关于宿主组织内MPC炎症信号以及细胞移植存活和少突胶质细胞分化时间点的重要新数据。这些结果表明，MPC移植可以通过控制循环炎症反应和局部组织环境来改变脊髓内移植的治疗窗口。
