Tsuji Shoichiro, Kuramoto Yoji, Rajbhandari Saujanya, Takeda Yuki, Yamahara Kenichi, Yoshimura Shinichi
Department of Neurosurgery, Hyogo Medical University, Hyogo, Japan.
Laboratory of Molecular and Cellular Therapy, Institute for Advanced Medical Sciences, Hyogo Medical University, Hyogo, Japan.
Front Cell Dev Biol. 2024 Sep 11;12:1464727. doi: 10.3389/fcell.2024.1464727. eCollection 2024.
Spinal cord injury (SCI) leads to severe disabilities and remains a significant social and economic challenge. Despite advances in medical research, there are still no effective treatments for SCI. Human amnion-derived mesenchymal stem cells (hAMSCs) have shown potential due to their anti-inflammatory and neuroprotective effects. This study evaluates the therapeutic potential of intravenously administered hAMSCs in SCI models.
Three days after induction of SCI with forceps calibrated with a 0.2 mm gap, hAMSCs or vehicle were administered intravenously. Up to 4 weeks of SCI induction, motor function was assessed by scores on the Basso Mouse Locomotor Scale (BMS) and the Basso-Beattie-Bresnahan Scale (BBB), and sensory function by hindlimb withdrawal reflex using von Frey filaments. Six weeks after SCI induction, gait function was assessed using three-dimensional motion analysis. Immunohistochemistry, polymerase chain reaction (PCR), flow cytometry, and ELISA assay were performed to clarify the mechanisms of functional improvement.
The hAMSC treatment significantly improved sensory response and gait function. In the SCI site, immunohistochemistry showed a reduction in Iba1-positive cells and PCR revealed decreased TNFα and increased BDNF levels in the hAMSC-treated group. In assessing the systemic inflammatory response, hAMSC treatment reduced monocytic bone marrow-derived suppressor cells (M-MDSCs) and Ly6C-positive inflammatory macrophages in the bone marrow by flow cytometry and serum NO levels by ELISA assay.
This study demonstrates the therapeutic potential of the hAMSC in SCI, with improvements in gait and sensory functions and reduced inflammation both locally and systemically. The findings support further investigation of the hAMSC as a potential treatment for SCI, focusing on their ability to modulate inflammation and promote neuroprotection.
脊髓损伤(SCI)会导致严重残疾,仍然是一项重大的社会和经济挑战。尽管医学研究取得了进展,但对于SCI仍没有有效的治疗方法。人羊膜间充质干细胞(hAMSCs)因其抗炎和神经保护作用而显示出潜力。本研究评估静脉注射hAMSCs在SCI模型中的治疗潜力。
在用间隙为0.2毫米的镊子诱导SCI三天后,静脉注射hAMSCs或赋形剂。在诱导SCI后的4周内,通过Basso小鼠运动量表(BMS)和Basso-Beattie-Bresnahan量表(BBB)评分评估运动功能,使用von Frey细丝通过后肢退缩反射评估感觉功能。在诱导SCI六周后,使用三维运动分析评估步态功能。进行免疫组织化学、聚合酶链反应(PCR)、流式细胞术和ELISA测定以阐明功能改善的机制。
hAMSC治疗显著改善了感觉反应和步态功能。在SCI部位,免疫组织化学显示Iba1阳性细胞减少,PCR显示hAMSC治疗组中TNFα水平降低,BDNF水平升高。在评估全身炎症反应时,hAMSC治疗通过流式细胞术减少了骨髓中的单核细胞骨髓来源抑制细胞(M-MDSCs)和Ly6C阳性炎性巨噬细胞,并通过ELISA测定降低了血清NO水平。
本研究证明了hAMSC在SCI中的治疗潜力,改善了步态和感觉功能,并减少了局部和全身的炎症。这些发现支持进一步研究hAMSC作为SCI的潜在治疗方法,重点关注其调节炎症和促进神经保护的能力。