The leading edge: Emerging neuroprotective and neuroregenerative cell-based therapies for spinal cord injury.,STEM CELLS Translational Medicine

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The leading edge: Emerging neuroprotective and neuroregenerative cell-based therapies for spinal cord injury.
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2020-07-21 , DOI: 10.1002/sctm.19-0135
Christopher S Ahuja _{1,

2,

3} , Andrea Mothe ₃ , Mohamad Khazaei ₃ , Jetan H Badhiwala ₁ , Emily A Gilbert ₄ , Derek van der Kooy ₅ , Cindi M Morshead _{2,

4,

6} , Charles Tator _{1,

2,

3} , Michael G Fehlings _{1,

2,

3}

Affiliation

Spinal cord injuries (SCIs) are associated with tremendous physical, social, and financial costs for millions of individuals and families worldwide. Rapid delivery of specialized medical and surgical care has reduced mortality; however, long‐term functional recovery remains limited. Cell‐based therapies represent an exciting neuroprotective and neuroregenerative strategy for SCI. This article summarizes the most promising preclinical and clinical cell approaches to date including transplantation of mesenchymal stem cells, neural stem cells, oligodendrocyte progenitor cells, Schwann cells, and olfactory ensheathing cells, as well as strategies to activate endogenous multipotent cell pools. Throughout, we emphasize the fundamental biology of cell‐based therapies, critical features in the pathophysiology of spinal cord injury, and the strengths and limitations of each approach. We also highlight salient completed and ongoing clinical trials worldwide and the bidirectional translation of their findings. We then provide an overview of key adjunct strategies such as trophic factor support to optimize graft survival and differentiation, engineered biomaterials to provide a support scaffold, electrical fields to stimulate migration, and novel approaches to degrade the glial scar. We also discuss important considerations when initiating a clinical trial for a cell therapy such as the logistics of clinical‐grade cell line scale‐up, cell storage and transportation, and the delivery of cells into humans. We conclude with an outlook on the future of cell‐based treatments for SCI and opportunities for interdisciplinary collaboration in the field.

中文翻译：

前沿：针对脊髓损伤的新兴神经保护和神经再生细胞疗法。

脊髓损伤（SCI）给全世界数以百万计的个人和家庭带来巨大的身体、社会和经济损失。快速提供专业医疗和外科护理降低了死亡率；然而，长期功能恢复仍然有限。基于细胞的疗法代表了一种令人兴奋的 SCI 神经保护和神经再生策略。本文总结了迄今为止最有前途的临床前和临床细胞方法，包括间充质干细胞、神经干细胞、少突胶质细胞祖细胞、雪旺细胞和嗅鞘细胞的移植，以及激活内源性多能细胞库的策略。自始至终，我们都强调细胞疗法的基本生物学、脊髓损伤病理生理学的关键特征以及每种方法的优点和局限性。我们还重点介绍了全球已完成和正在进行的临床试验及其研究结果的双向转化。然后，我们概述了关键的辅助策略，例如优化移植物存活和分化的营养因子支持、提供支持支架的工程生物材料、刺激迁移的电场以及降解神经胶质疤痕的新方法。我们还讨论了启动细胞疗法临床试验时的重要考虑因素，例如临床级细胞系放大的物流、细胞储存和运输以及将细胞输送到人体。最后，我们对 SCI 细胞治疗的未来以及该领域跨学科合作的机会进行了展望。

更新日期：2020-07-21

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