Yin Tsung-Cheng, Lin Hung-Sheng, Sung Pei-Hsun, Chiang John Y, Yang Chien-Hui, Yip Hon-Kan, Chen Kuan-Hung
Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan.
Division of Neurology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan.
J Mol Histol. 2025 Jan 6;56(1):66. doi: 10.1007/s10735-024-10344-9.
This study tested whether combined ceftriaxone and adipose-derived mesenchymal stem cells (ADMSCs) would defend the spinal cord against acute spinal infection (ASI) in rodent. Adult-Male-SD rats were grouped into groups 1 (SC)/2 (ASI)/3 (ASI + ceftriaxone from days 2 to 28 after ASI induction)/4 (ASI + allogenic ADMSCs from day 2 for a total of 3 doses/3 consecutive intervals by intravenous injection)/5 (ASI + combined ceftriaxone and ADMSC) and spinal cord tissues were harvested by day 28. Circulatory levels of TNF-α/IL-6 at days 7 and 28, and these two parameters in spinal fluid at day 28 were lowest in group 1, highest in group 2, significantly lower in group 5 than in groups 3/4, and significantly lower in group 3 than in group 4 (all p < 0.0001). The day-28 bacterial colony formation unit (CFU) in vertebral bone and circulatory WBC counts at the time points of days 7/14/28, and the protein expressions of upstream (TRL-2/TLR-4/MYD88/TRAF6/IKKα/IKKβ /IKBβ/p-NF-κB) and downstream (IL-1β/IL-6/TNF-α/IFN-γ/iNOS) inflammatory signalings displayed a similar pattern of inflammatory biomarkers in spinal fluid among the groups (all p < 0.0001). By day 28, the bone injury score/bone marrow density/ratio of bone volume (BV) to the bone tissue volume (TV)/ratio of bone surface (BS) to BV/ratio of BS to bone TV/trabecular number exhibited an opposite, whereas the trabecular space exhibited an alike pattern of inflammatory biomarkers among the groups (all p < 0.0001). Combined ceftriaxone and ADMSCs therapy offered an additional benefit on protecting the vertebral bone/spinal cord against ASI damage.
本研究测试了联合使用头孢曲松和脂肪间充质干细胞（ADMSCs）是否能保护啮齿动物脊髓免受急性脊髓感染（ASI）。成年雄性SD大鼠被分为1组（假手术组）/2组（急性脊髓感染组）/3组（急性脊髓感染后第2天至28天给予头孢曲松）/4组（急性脊髓感染后第2天开始共3剂/连续3个间隔静脉注射同种异体ADMSCs）/5组（急性脊髓感染+联合使用头孢曲松和ADMSC），并在第28天采集脊髓组织。第7天和第28天循环中TNF-α/IL-6水平，以及第28天脑脊液中这两个参数，在1组中最低，在2组中最高，5组显著低于3/4组，且3组显著低于4组（所有p<0.0001）。第28天椎骨中的细菌菌落形成单位（CFU）以及第7/14/28天时间点的循环白细胞计数，和上游（TRL-2/TLR-4/MYD88/TRAF6/IKKα/IKKβ /IKBβ/p-NF-κB）和下游（IL-1β/IL-6/TNF-α/IFN-γ/iNOS）炎症信号的蛋白表达在各组脑脊液中显示出类似的炎症生物标志物模式（所有p<0.0001）。到第28天，骨损伤评分/骨髓密度/骨体积（BV）与骨组织体积（TV）之比/骨表面（BS）与BV之比/BS与骨TV之比/小梁数量在各组中呈现相反趋势，而小梁间隙呈现相似的炎症生物标志物模式（所有p<0.0001）。联合使用头孢曲松和ADMSCs疗法在保护椎骨/脊髓免受急性脊髓感染损伤方面具有额外益处。
