Oliveira J Miguel, Carvalho Luisa, Silva-Correia Joana, Vieira Sílvia, Majchrzak Malgorzata, Lukomska Barbara, Stanaszek Luiza, Strymecka Paulina, Malysz-Cymborska Izabela, Golubczyk Dominika, Kalkowski Lukasz, Reis Rui L, Janowski Miroslaw, Walczak Piotr
3B´s Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence, Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra, 4805-017 Barco, Guimarães Portugal.
2ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal.
NPJ Regen Med. 2018 Apr 4;3:8. doi: 10.1038/s41536-018-0046-3. eCollection 2018.
The prospects for cell replacement in spinal cord diseases are impeded by inefficient stem cell delivery. The deep location of the spinal cord and complex surgical access, as well as densely packed vital structures, question the feasibility of the widespread use of multiple spinal cord punctures to inject stem cells. Disorders characterized by disseminated pathology are particularly appealing for the distribution of cells globally throughout the spinal cord in a minimally invasive fashion. The intrathecal space, with access to a relatively large surface area along the spinal cord, is an attractive route for global stem cell delivery, and, indeed, is highly promising, but the success of this approach relies on the ability of cells (1) to survive in the cerebrospinal fluid (CSF), (2) to adhere to the spinal cord surface, and (3) to migrate, ultimately, into the parenchyma. Intrathecal infusion of cell suspension, however, has been insufficient and we postulate that embedding transplanted cells within hydrogel scaffolds will facilitate reaching these goals. In this review, we focus on practical considerations that render the intrathecal approach clinically viable, and then discuss the characteristics of various biomaterials that are suitable to serve as scaffolds. We also propose strategies to modulate the local microenvironment with nanoparticle carriers to improve the functionality of cellular grafts. Finally, we provide an overview of imaging modalities for in vivo monitoring and characterization of biomaterials and stem cells. This comprehensive review should serve as a guide for those planning preclinical and clinical studies on intrathecal stem cell transplantation.
干细胞递送效率低下阻碍了脊髓疾病细胞替代疗法的前景。脊髓位置深、手术入路复杂，且重要结构密集，这使得广泛采用多次脊髓穿刺注射干细胞的可行性受到质疑。以弥漫性病理改变为特征的疾病，对于以微创方式在整个脊髓中全局分布细胞而言，特别具有吸引力。鞘内空间可接触到沿脊髓相对较大的表面积，是全局递送干细胞的一条有吸引力的途径，而且确实很有前景，但这种方法的成功依赖于细胞能够（1）在脑脊液（CSF）中存活，（2）黏附于脊髓表面，以及（3）最终迁移至实质内。然而，鞘内输注细胞悬液一直效果不佳，我们推测将移植细胞嵌入水凝胶支架将有助于实现这些目标。在本综述中，我们重点关注使鞘内途径具有临床可行性的实际考量因素，然后讨论适合用作支架的各种生物材料的特性。我们还提出了利用纳米颗粒载体调节局部微环境以改善细胞移植功能的策略。最后，我们概述了用于体内监测和表征生物材料及干细胞的成像方式。这篇全面的综述应为那些计划开展鞘内干细胞移植临床前和临床研究的人员提供指导。
