Hydrogel-based scaffolds to support intrathecal stem cell transplantation as a gateway to the spinal cord: clinical needs, biomaterials, and imaging technologies.

NPJ Regen Med. 2018 Apr 4;3:8. doi: 10.1038/s41536-018-0046-3. eCollection 2018.

Oliveira JM1,2,3, Carvalho L1,2, Silva-Correia J1,2, Vieira S1,2, Majchrzak M4, Lukomska B4, Stanaszek L4, Strymecka P4, Malysz-Cymborska I5, Golubczyk D5, Kalkowski L5, Reis RL1,2,3, Janowski M4,6,7, Walczak P5,6,7.

1 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.

2 2ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal.

3 3The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, 4805-017 Barco, Guimarães Portugal.

4 4NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

5 5Department of Neurology and Neurosurgery, School of Medicine, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland.

6 6Russel H, Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD USA.

7 7Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD USA.

Hydrogel-based scaffolds to support intrathecal stem cell transplantation as a gateway to the spinal cord: clinical needs, biomaterials, and imaging technologies.

ABSTRACT

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.

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