Spinal Repair Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London, UK.
Imperial College Healthcare NHS Trust, London, UK.
Cell Transplant. 2023 Jan-Dec;32:9636897231199319. doi: 10.1177/09636897231199319.
In the past decades, the properties of olfactory ensheathing cells (OECs) have been widely investigated. Studies have shown that transplantation of OECs cultured from the olfactory bulb mediates axonal regeneration, remyelination and restores lost functions in experimental central nervous system (CNS) injury models. Autologously sourcing the cells from the nasal mucosa or the olfactory bulb to treat patients with spinal cord injuries would be ideal, but the cell yield achieved may be inadequate to cover the surface area of the lesions typically encountered in human spinal cord contusion injuries. Therefore, banking allogenic cryopreserved olfactory bulb cells from donors or generating cell lines could provide a marked increase in cell stock available for transplantation. This study is undertaken in two control and two intervention groups. The control groups have lesions alone and lesions with collagen gel but without cells. The intervention groups have either transplantation of primary cultured olfactory bulb OECs (bOECs) encapsulated in collagen gel or cryopreserved bulb OECs (CbOECs) encapsulated in collagen gel. Here, we report that transplantation of cryopreserved rat bOECs encapsulated in collagen restored the loss of function in a vertical climbing test in a unilateral C6-T1 dorsal root injury model. The loss of function returns in 80% of rats with injuries in about 3 weeks comparable to that we observed after transplantation of primary cultured bOECs. The regeneration axons induced by the transplant are identified by neurofilament antibodies and ensheathed by OECs. Our results indicate that cryopreserved OECs retain their properties of inducing axon regeneration and restoring loss of function in the experimental model. This is a step forward to translate the research into future clinical applications.
在过去的几十年中，嗅鞘细胞（OECs）的特性已经得到了广泛的研究。研究表明，移植从嗅球培养的 OECs 可介导轴突再生、髓鞘再生并恢复实验性中枢神经系统（CNS）损伤模型中丧失的功能。从鼻黏膜或嗅球自体采集细胞来治疗脊髓损伤患者是理想的，但从病变部位获得的细胞产量可能不足以覆盖人脊髓挫伤损伤中常见的病变面积。因此，从供体银行同种异体冷冻保存的嗅球细胞或生成细胞系可显著增加可用于移植的细胞库存。本研究分为两组对照和两组干预组。对照组只有病变和病变伴胶原凝胶但无细胞。干预组分别为移植原代培养嗅球 OECs（bOECs）包封在胶原凝胶中或冷冻保存的嗅球 OECs（CbOECs）包封在胶原凝胶中。在这里，我们报告说，移植冷冻保存的大鼠 bOECs 包封在胶原凝胶中可恢复单侧 C6-T1 背根损伤模型中垂直攀爬试验的功能丧失。约 3 周后，80%的损伤大鼠恢复功能，与我们观察到的原代培养 bOECs 移植后的恢复情况相当。移植诱导的再生轴突通过神经丝抗体识别并被 OECs 包绕。我们的结果表明，冷冻保存的 OECs 保留了诱导轴突再生和恢复实验模型中功能丧失的特性。这是将研究转化为未来临床应用的重要一步。
