The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Department of Regeneration of Sensorimotor Systems, Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
Cells. 2021 May 25;10(6):1316. doi: 10.3390/cells10061316.
Mesenchymal stromal cells (MSC) are used for cell therapy for spinal cord injury (SCI) because of their ability to support tissue repair by paracrine signaling. Preclinical and clinical research testing MSC transplants for SCI have revealed limited success, which warrants the exploration of strategies to improve their therapeutic efficacy. MSC are sensitive to the microenvironment and their secretome can be altered in vitro by exposure to different culture media. Priming MSC with inflammatory stimuli increases the expression and secretion of reparative molecules. We studied the effect of macrophage-derived inflammation priming on MSC transplants and of primed MSC (pMSC) acute transplants (3 days) on spinal cord repair using an adult rat model of moderate-severe contusive SCI. We found a decrease in long-term survival of pMSC transplants compared with unprimed MSC transplants. With a pMSC transplant, we found significantly more anti-inflammatory macrophages in the contusion at 4 weeks post transplantation (wpt). Blood vessel presence and maturation in the contusion at 1 wpt was similar in rats that received pMSC or untreated MSC. Nervous tissue sparing and functional recovery were similar across groups. Our results indicate that macrophage-derived inflammation priming does not increase the overall therapeutic potential of an MSC transplant in the adult rat contused spinal cord.
间充质基质细胞（MSC）因其旁分泌信号作用支持组织修复的能力，被用于治疗脊髓损伤（SCI）的细胞疗法。针对 SCI 进行的 MSC 移植的临床前和临床研究显示其疗效有限，这就需要探索提高其治疗效果的策略。MSC 对微环境敏感，其分泌组可通过暴露于不同的培养基在体外发生改变。用炎症刺激物对 MSC 进行预刺激可增加修复分子的表达和分泌。我们使用成年大鼠中度至重度挫伤性 SCI 模型研究了巨噬细胞来源的炎症预刺激对 MSC 移植的影响，以及急性移植（3 天）后预刺激 MSC（pMSC）对脊髓修复的影响。与未预刺激的 MSC 移植相比，我们发现 pMSC 移植的长期存活率降低。在移植后 4 周（wpt），我们发现与接受未处理的 MSC 移植的大鼠相比，pMSC 移植中有更多的抗炎性巨噬细胞存在于挫伤处。在接受 pMSC 或未处理的 MSC 移植的大鼠中，在 1 wpt 时，挫伤处的血管存在和成熟情况相似。神经组织保留和功能恢复在各组之间相似。我们的结果表明，巨噬细胞来源的炎症预刺激并没有增加成年大鼠挫伤性脊髓中 MSC 移植的整体治疗潜力。
