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Spinal cord repair and regeneration
Published in David M. Gardiner, Regenerative Engineering and Developmental Biology, 2017
The lack of successful CNS regeneration in mammals makes it difficult to identify the best strategies for improving functional recovery in the clinical setting. At present, bioengineering approaches are taking a lead role. Autologous peripheral nerve grafts are being used successfully to bridge spinal lesions and promote regeneration in mammalian SCI models (Houle et al., 2006; Cote et al., 2011; Khaing and Schmidt, 2012). Cellular transplantation therapies, including grafting of neural stem/progenitor cells to promote neuron replacement, olfactory ensheathing cells to promote reorganization of the glial scar and axon regrowth, and Schwann cells to promote remyelination, are being developed (Tetzlaff et al., 2011; Roet and Verhaagen, 2014). A number of molecular manipulations and delivery systems are also being considered, including those that increase the levels of the signaling molecule cyclic AMP (which improves CNS axon regeneration in many SCI models [Domeniconi and Filbin, 2005; Hannila and Filbin, 2008]), as are stimulation-based interventions (Roy et al., 2012). Despite recent progress, many questions remain about which treatment(s) will best support CNS repair and regeneration, because most single manipulations have modest effects, and therefore, no individual treatment has, as of now, been the key to a full recovery. Furthermore, reproducibility of experimental results has been problematic, in part, due to differences in the models and lack of clear documentation on the data collection methods, necessitating replication studies and broader re-evaluation (Steward et al., 2012; Biering-Sorensen et al., 2015). Thus, we are at a crossroad in the field of SCI and in need of higher throughput analyses to determine the best combinations of treatments that could promote recovery from SCI. Here, non-mammalian models could provide some advantages for delineating the basic, conserved mechanisms that support CNS repair and regeneration, which when complemented with mammalian studies, could contribute to solving some of the field’s biggest problems.
In vitro biocompatibility study of EDC/NHS cross-linked silk fibroin scaffold with olfactory ensheathing cells
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Shengwen Li, Peng Wu, Zhongqing Ji, Yu Zhang, Peng Zhang, Yongqing He, Yixin Shen
Olfactory ensheathing cells (OECs) are potential candidates for cell transplantation in central nervous system (CNS) repair [1–3]. The main mechanisms that contribute to functional recovery are neuroprotection and the promotion of sprouting from intact fibers [4]. However, anatomical evidence suggests that axons can regenerate within a transplant but cannot cross a lesion or reconnect with neurons on the opposite side of the lesion [5]. Therefore, growing recognition refers that OEC transplants can perform the essential function of replacing lesion cavities with a growth-permissive scaffold, achieving long-distance and functional axon regeneration across the lesion [6,7].
Design of peptide-PEG-Thiazole bound polypyrrole supramolecular assemblies for enhanced neuronal cell interactions
Published in Soft Materials, 2021
Sarah M. Broas, Ipsita A. Banerjee
Cells derived from mouse olfactory bulb were chosen for this study as olfactory bulbs are rich in olfactory ensheathing cells (OECs), which are well-known to support neural regeneration by promoting cell–cell interaction, axon growth and restoration and have been attempted to be utilized for spinal cord regeneration applications[73] Furthermore, olfactory bulbs are also a source for mitral and tufted cells play a key role in making synaptic contacts. To examine the cell viability of the assemblies, we carried out Trypan Blue exclusion assay. As shown in Figure 6, the results demonstrate cell proliferation studies carried out over a period of 48 h. We compared the cell growth of the peptide bound Lam-PEG-Thiazole assemblies, Lam-PEG-Thiazole-PPy assemblies, neat PPy and neat Lam peptide. At 2 μg/mL and 5 μg/mL, cell counts were comparable to the control both in the presence of Lam-PEG-Thiazole assemblies. For Lam-PEG-Thiazole-PPy assemblies cell counts were marginally lower. For the 2 μg/mL proliferation was found to be 2% lower and at 5 μg/mL the proliferation was found to be 5% lower. The marginal slower proliferation observed in the presence of Lam-PEG-Thiazole-PPy observed is likely due to the fact that the cells may aggregate between monolayers along the surface at higher amounts of PPy bound assemblies. In comparison, neat PPy showed a higher cytotoxicity, and viability was found to be14% lower than that of the control. These results corroborate with previous works where it has been shown that at higher concentrations polypyrrole is known to cause some cytotoxicity.[74] Thus, the Lam-PEG-Thiazole-PPy may be capable of reducing the cytotoxicity of PPy alone. The neat LAM peptide however had similar growth as that of the control cells further confirming that the peptide alone does not exert any cytotoxicity.