Cell therapy offers significant promise for traumatic spinal cord injury (SCI), which despite many medical advances, has limited treatment strategies. Able to address the multifactorial and dynamic pathophysiology of SCI, cells present various advantages over standard pharmacological approaches. However, the use of live cells is also severely hampered by logistical and practical considerations. These include specialized equipment and expertise, standardization of cell stocks, sustained cell viability post-thawing, and cryopreservation-induced delayed-onset cell death. For this reason, we suggest a novel and clinically translatable alternative to live-cell systemic infusion, which retains the efficacy of the latter while overcoming many of its limitations. This strategy involves the administration of concentrated cell secretome and exploits the trophic mechanism by which stromal cells function. In this study, we compare the efficacy of intravenously delivered concentrated conditioned media (CM) from human umbilical cord matrix cells (HUCMCs), bone marrow mesenchymal stromal cells, as well as newborn and adult fibroblasts in a rat model of moderately severe cervical clip compression/contusion injury (C7-–T1, 35 g). This is further paired with a thorough profile of the CM cytokines, chemokines, and angiogenic factors. The HUCMC-derived CM was most effective at limiting acute (48 h post-SCI) vascular pathology, specifically lesion volume, and functional vascularity. Principle component analysis (PCA), hierarchical clustering, and interaction analysis of proteins highly expressed in the HUCMC secretome suggest involvement of the MAPK/ERK, JAK/STAT, and immune cell migratory pathways. This “secretotherapeutic” strategy represents a novel and minimally invasive method to target multiple organ systems and several pathologies shortly after traumatic SCI.

中文翻译：

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利用间充质基质细胞的分泌组治疗创伤性脊髓损伤：多细胞比较和体内疗效评估。

细胞疗法为创伤性脊髓损伤 (SCI) 提供了重要的前景，尽管有许多医学进步，但治疗策略有限。能够解决 SCI 的多因素和动态病理生理学，细胞比标准药理学方法具有多种优势。然而，活细胞的使用也受到后勤和实际考虑的严重阻碍。其中包括专门的设备和专业知识、细胞库的标准化、解冻后的持续细胞活力以及冷冻保存引起的延迟性细胞死亡。出于这个原因，我们提出了一种新的、临床可转化的活细胞全身输注替代方案，它保留了后者的功效，同时克服了它的许多局限性。该策略涉及施用浓缩的细胞分泌组并利用基质细胞发挥功能的营养机制。在这项研究中，我们比较了来自人脐带基质细胞 (HUCMC)、骨髓间充质基质细胞以及新生儿和成人成纤维细胞的静脉输送浓缩条件培养基 (CM) 在中重度宫颈夹压迫大鼠模型中的功效/挫伤（C7--T1，35 克）。这进一步与 CM 细胞因子、趋化因子和血管生成因子的全面概况相结合。HUCMC 衍生的 CM 在限制急性（SCI 后 48 小时）血管病理学方面最有效，特别是病变体积和功能性血管分布。主成分分析（PCA），层次聚类，HUCMC 分泌组中高度表达的蛋白质和相互作用分析表明参与了 MAPK/ERK、JAK/STAT 和免疫细胞迁移途径。这种“分泌治疗”策略代表了一种新颖的微创方法，可在创伤性 SCI 后不久针对多个器官系统和多种病理。