Departamento de Química Biológica, Cátedra de Química Biológica Patológica. Junín 956, Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina; Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Junín 956, CONICET, Universidad de Buenos Aires. Buenos Aires, Argentina.
Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Junín 956, CONICET, Universidad de Buenos Aires. Buenos Aires, Argentina.
Acta Biomater. 2021 Aug;130:234-247. doi: 10.1016/j.actbio.2021.05.050. Epub 2021 May 31.
Traumatic peripheral nerve injuries constitute a huge concern to public health. Nerve damage leads to a decrease or even loss of mobility of the innervated area. Adult stem cell therapies have shown some encouraging results and have been identified as promising treatment candidates for nerve regeneration. A major obstacle to that approach is securing a sufficient number of cells at the injured site to produce measurable therapeutic effects. The present work tackles this issue and demonstrates enhanced nerve regeneration ability promoted by magnetic targeted cell therapy in an in vivo Wallerian degeneration model. To this end, adipose-derived mesenchymal stem cells (AdMSC) were loaded with citric acid coated superparamagnetic iron oxide nanoparticles (SPIONs), systemically transplanted and magnetically recruited to the injured sciatic nerve. AdMSC arrival to the injured nerve was significantly increased using magnetic targeting and their beneficial effects surpassed the regenerative properties of the stand-alone cell therapy. AdMSC-SPIONs group showed a partially conserved nerve structure with many intact myelinated axons. Also, a very remarkable restoration in myelin basic protein organization, indicative of remyelination, was observed. This resulted in an improvement in nerve conduction, demonstrating functional recovery. In summary, our results demonstrate that magnetically assisted delivery of AdMSC, using a non-invasive and non-traumatic method, is a highly promising strategy to promote cell recruitment and sciatic nerve regeneration after traumatic injury. Last but not least, our results validate magnetic targeting in vivo exceeding previous reports in less complex models through cell magnetic targeting in vitro and ex vivo. STATEMENT OF SIGNIFICANCE: Traumatic peripheral nerve injuries constitute a huge public health concern. They can lead to a decrease or even loss of mobility of innervated areas. Due to their complex pathophysiology, current pharmacological and surgical approaches are only partially effective. Cell-based therapies have emerged as a useful tool to achieve full tissue regeneration. However, a major bottleneck is securing enough cells at injured sites. Therefore, our proposal combining biological (adipose derived mesenchymal stem cells) and nanotechnological strategies (magnetic targeting) is of great relevance, reporting the first in vivo experiments involving "magnetic stem cell" targeting for peripheral nerve regeneration. Using a non-invasive and non-traumatic method, cell recruitment in the injured nerve was improved, fostering nerve remyelination and functional recovery.
外伤性周围神经损伤对公共健康构成了巨大的威胁。神经损伤会导致支配区域的运动功能下降甚至丧失。成人干细胞疗法已经显示出一些令人鼓舞的结果，并被确定为神经再生有前途的治疗候选物。该方法的一个主要障碍是在损伤部位获得足够数量的细胞，以产生可衡量的治疗效果。本研究解决了这一问题，并在体内 Wallerian 变性模型中证明了磁靶向细胞疗法促进神经再生的能力。为此，将柠檬酸涂层超顺磁性氧化铁纳米粒子（SPION）负载到脂肪来源的间充质干细胞（AdMSC）中，系统移植并通过磁场募集到损伤的坐骨神经。通过磁靶向显著增加了 AdMSC 到达损伤神经的数量，并且其有益效果超过了单独细胞疗法的再生特性。AdMSC-SPION 组表现出部分保留的神经结构，有许多完整的髓鞘轴突。此外，还观察到髓鞘碱性蛋白组织的显著恢复，表明发生了髓鞘再生。这导致神经传导的改善，表明功能恢复。总之，我们的结果表明，使用非侵入性和非创伤性方法进行磁辅助 AdMSC 递送是一种很有前途的策略，可以促进外伤性损伤后细胞募集和坐骨神经再生。最后但同样重要的是，我们的结果通过体外和离体的细胞磁靶向验证了体内的磁靶向，超过了以前在较简单模型中的报告。
外伤性周围神经损伤对公共健康构成了巨大的威胁。它们会导致支配区域的运动功能下降甚至丧失。由于其复杂的病理生理学，目前的药物和手术方法仅部分有效。基于细胞的疗法已成为实现组织完全再生的有用工具。然而，一个主要的瓶颈是在损伤部位获得足够的细胞。因此，我们提出的结合生物（脂肪来源的间充质干细胞）和纳米技术（磁靶向）的策略非常重要，首次报道了涉及外周神经再生的“磁性干细胞”靶向的体内实验。使用非侵入性和非创伤性方法，改善了损伤神经中的细胞募集，促进了神经髓鞘再生和功能恢复。
