Neuroimmunology Research Group, Keio University School of Medicine, Tokyo 160-8582, Japan.
Neurosci Res. 2009 Dec;65(4):384-92. doi: 10.1016/j.neures.2009.08.016. Epub 2009 Sep 6.
We previously reported that implantation of dendritic cells (DCs) into the injured site activates neural stem/progenitor cells (NSPCs) and promotes functional recovery after spinal cord injury (SCI) in mice. Working toward clinical application of DC therapy for SCI, we analyzed whether DCs promote functional recovery after SCI in a non-human primate, the common marmoset (CM). CMs are usually born as dizygotic twins. They are thus natural bone marrow and peripheral blood chimeras due to sharing of the placental circulation between dizygotic twins, leading to functional immune tolerance. In this study, to identify adequate CM donor-and-host pairs, mixed leukocyte reaction (MLR) assays were performed. Then, CM-DCs were generated from the bone marrow of the twin selected to be donor and transplanted into the injured site of the spinal cord of the other twin selected to be host, 7 days after injury. Histological analyses revealed fewer areas of demyelination around the injured site in DC-treated CMs than in controls. Immunohistochemical analysis showed that more motor neurons and corticospinal tracts were preserved after SCI in DC-treated CMs. Motor functions were evaluated using three different behavior tests and earlier functional recovery was observed in DC-treated CMs. These results suggest DC therapy to possibly be beneficial in primates with SCI and that this treatment has potential for clinical application.
我们之前报道过，将树突状细胞（DC）植入损伤部位可以激活神经干细胞/祖细胞（NSPCs），促进脊髓损伤（SCI）后小鼠的功能恢复。为了将 DC 疗法应用于 SCI 的临床治疗，我们分析了 DC 是否能促进非人类灵长类动物——普通狨猴（CM）的 SCI 后功能恢复。CM 通常是双胎的。由于双胎之间胎盘循环共享，它们成为天然的骨髓和外周血嵌合体，从而导致功能性免疫耐受。在这项研究中，为了确定合适的 CM 供体和受体对，进行了混合淋巴细胞反应（MLR）测定。然后，从选定为供体的双胞胎的骨髓中生成 CM-DC，并在损伤后 7 天移植到选定为受体的另一个双胞胎的脊髓损伤部位。组织学分析显示，在 DC 处理的 CM 中，损伤部位周围脱髓鞘区域较少。免疫组织化学分析显示，在 DC 处理的 CM 中，运动神经元和皮质脊髓束在 SCI 后得到了更好的保留。通过三种不同的行为测试评估运动功能，在 DC 处理的 CM 中观察到更早的功能恢复。这些结果表明，DC 疗法可能对 SCI 的灵长类动物有益，并且这种治疗方法具有临床应用的潜力。
