Abstract
Spinal cord injury (SCI), resulting in para- and tetraplegia caused by the partial or complete disruption of descending motor and ascending sensory neurons, represents a complex neurological condition that remains incurable. Following SCI, numerous obstacles comprising of the loss of neural tissue (neurons, astrocytes, and oligodendrocytes), formation of a cavity, inflammation, loss of neuronal circuitry and function must be overcome. Given the multifaceted primary and secondary injury events that occur with SCI treatment options are likely to require combinatorial therapies. While several methods have been explored, only the intersection of two, cell transplantation and biomaterial implantation, will be addressed in detail here. Owing to the constant advance of cell culture technologies, cell-based transplantation has come to the forefront of SCI treatment in order to replace/protect damaged tissue and provide physical as well as trophic support for axonal regrowth. Biomaterial scaffolds provide cells with a protected environment from the surrounding lesion, in addition to bridging extensive damage and providing physical and directional support for axonal regrowth. Moreover, in this combinatorial approach cell transplantation improves scaffold integration and therefore regenerative growth potential. Here, we review the advances in combinatorial therapies of Schwann cells (SCs), astrocytes, olfactory ensheathing cells (OECs), mesenchymal stem cells, as well as neural stem and progenitor cells (NSPCs) with various biomaterial scaffolds.
Highlights
Traumatic spinal cord injury (SCI) results in the disruption of neuronal circuitry leading to the partial or complete loss of motor control, autonomic function and sensory input
Further work needs to be done to elucidate if this moved the glial limitans further down the cord to the host spinal injection site of Schwann cells (SCs) or if growth past the grafted SCs is possible. It was found in a 4 mm rat T8 complete transection that the unique combination of SC in fluid Matrigel in a polyacrylonitrile and polyvinylchloride copolymers (PAN/PVC) single channel scaffold, with olfactory ensheathing cells (OECs) grafting in host parenchyma surrounding the lesion (Category II, III, and IV) and the delivery of ChABC led to functional improvement (BBB motor recovery score; up to 6 at 9 weeks vs. 2 with no treatment) (Fouad et al, 2005)
While it is unclear which method has a greater beneficial effect, it was noted that the Gelfoam delayed the migration of the astrocytes from the lesion site and that cell-seeded Gelfoam appeared to be better integrated into the lesion site than Gelfoam alone
Summary
Traumatic spinal cord injury (SCI) results in the disruption of neuronal circuitry leading to the partial or complete loss of motor control, autonomic function and sensory input. Many studies showed a certain degree of morphological changes partially accompanied by behavioral improvements in various animal models (Fouad et al, 2005; Blesch and Tuszynski, 2009; Franz et al, 2012; McCall et al, 2012; Zhao et al, 2013; Danilov and Steward, 2015; Gomes-Osman et al, 2016; Kadoya et al, 2016) Amongst these studies, cell-based transplantation has been considered as a promising therapeutic strategy due to: (1) direct replacement of the damaged neural tissue, (2) neuroprotective properties for spared neuronal connections, and (3) providing a permissive and supportive cellular growth substrate for axonal regrowth and/or plasticity (Ohta et al, 2004; Feron et al, 2005; Granger et al, 2014; Kanno et al, 2015). Delivery of Chondroitin sulfate proteoglycan (CSPG) cleaving enzyme chondroitinase ABC
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