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Axonal Injury and Disease Progression in Multiple Sclerosis
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
The development of specific neuroprotective drugs aimed for MS patients constitute an important goal for MS research that requires appropriate animals models. The relapsing EAE model discussed above resembles MS in many aspects and may be suitable for testing the efficacy of such drugs.11,59 Promoting remyelination at an early stage of MS will restore conduction and, more important, may be neuroprotective since chronic demyelination can cause axonal degeneration. Possible avenues to obtain remyelination include enhancing endogenous CNS cells to repopulate and remyelinate lesions, or transplanting stem or progenitor cells into lesions. Bone marrow cells that can give rise to neuronal cells may provide an effective source of donor cells for transplantation that, in addition, will avoid controversial political issues associated with stem cells. Finally, the silent nature of early axonal loss and the lack of reliable surrogate markers of disease progression during RR-MS are major obstacles for testing future therapeutics. Surrogate markers of axonal loss are therefore needed to monitor patients with MS.
Aptamers as Therapeutic Tools in Neurological Diseases
Published in Rakesh N. Veedu, Aptamers, 2017
Lukas Aaldering, Shilpa Krishnan, Sue Fletcher, Stephen D. Wilton, Rakesh N. Veedu
Remyelination is a naturally occurring process in the body to restore damaged myelin sheaths after an MS attack. However, this restoration process often leads to only incomplete recovery [14]. Recently, a 40-nucleotide DNA aptamer was identified that exhibits affinity toward murine myelin [15]. It binds to multiple myelin components in vitro, and intraperitoneal (IP) injection in mice showed improved distribution and uptake in central nervous system (CNS) tissues. Furthermore, the aptamer promoted remyelination of CNS lesions in mice infected by Theiler’s virus [15]. Thus, this aptamer could prove valuable in the body recovery after an MS attack and could palliate MS symptoms.
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.
The role of feedback in the robotic-assisted upper limb rehabilitation in people with multiple sclerosis: a systematic review
Published in Expert Review of Medical Devices, 2023
Marialuisa Gandolfi, Stefano Mazzoleni, Giovanni Morone, Marco Iosa, Filippo Galletti, Nicola Smania
Functional recovery in MS is achieved and sustained by repair of damage through remyelination, with the resolution of inflammation and functional reorganization. Remyelination is essential for restoring axonal function after acute inflammatory demyelination [7]. Functional reorganization relies on molecular and cellular mechanisms to induce changes in systems-level functional responses involved in perception, action, and cognition [2]. Evidence for the reorganization of brain function after brain lesions comes from early studies on focal ischemic brain damage, where multiple mechanisms of brain plasticity at the molecular, synaptic, and cellular level support post-injury brain plasticity [8–10]. In brief, functional recovery after stroke involves perilesional remapping of cortical representations, functional reorganization in undamaged regions of the affected hemisphere, and activation of cortical areas in the unaffected hemisphere [8]. In the last decades, new insight into the functional reorganization processes in MS has improved our understanding of brain recovery in PwMS, generating novel hypotheses for potential intervention strategies [2]. Evidence supports a similar adaptive role for functional reorganization in PwMS, showing that neuroplasticity is preserved despite widespread pathology across all patient ages and stages of the disease [2,11,12]. However, as the disease advances toward secondary progression, patterns of functional reorganization show an increasingly bilateral distribution involving higher-control sensorimotor areas that are generally recruited for novel or complex tasks in healthy individuals [12].
A review on the recent progress, opportunities, and challenges of 4D printing and bioprinting in regenerative medicine
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Parvin Pourmasoumi, Armaghan Moghaddam, Saba Nemati Mahand, Fatemeh Heidari, Zahra Salehi Moghaddam, Mohammad Arjmand, Ines Kühnert, Benjamin Kruppke, Hans-Peter Wiesmann, Hossein Ali Khonakdar
Polypyrrole is another conductive polymer with high electrical conductivity and stability, biocompatibility, and facility for synthesis [43]. Vijayavenkataraman et al. [44] developed a new conductive bioink for neural tissue engineering. The hydrogel was based on collagen and polypyrrole block copolymer and polycaprolactone (PCL) (PPy-block-poly (caprolactone)) for encapsulating cells during 3D bioprinting. Their study aimed to overcome the previous problems of conductive hydrogels, such as non-biodegradability or long-term cytotoxicity of nano-metals. This system had elastic-solid behavior and the best continuous line, and 3D printing could be obtained at a printing speed of above 3 mm/s and 5 ml/min. Furthermore, adding PPy-block-PCL to collagen enhanced the mechanical properties and showed no cell cytotoxicity. Zhao et al. [45] suggested another electrical response construct for neural tissue engineering. Silk fibroin and polypyrrole conductive scaffolds were fabricated, and Schwann cells were cultured on the scaffolds’ surface after fabrication. An electrical stimulus was applied to the printed scaffold and improved cell viability, proliferation, and migration. Furthermore, neurotrophic factors expression was increased, and in-vivo investigations demonstrated better axonal regeneration and remyelination. In addition, extracellular signal-regulated kinase (ERK) as one of the mitogen activated protein kinases (MAPKs) signal pathways were activated by electrical response material. It is assumed that ERK is involved in neuronal plasticity and activation of MAPK signal pathway plays a critical regulatory role in controlling cytological activities. Therefore, this composite could serve as a promising candidate for bioprinting in peripheral nerve regeneration.