Interestingly, FM19G11 induces self-renewal of these ependymal stem cells grown under normoxia. Much has been uncovered concerning the function of reactive astrocytes in SCI, and research is ongoing on how to enhance their beneficial roles while minimizing their deleterious effects. J. Pathol. J. Comp. Characterization of the antibody response after cervical spinal cord injury. Age exacerbates microglial activation, oxidative stress, inflammatory and NOX2 gene expression, and delays functional recovery in a middle-aged rodent model of spinal cord injury. doi: 10.1093/brain/aws072, Chamankhah, M., Eftekharpour, E., Karimi-Abdolrezaee, S., Boutros, P. C., San-Marina, S., and Fehlings, M. G. (2013). doi: 10.3727/096368912x662408, Herrmann, J. E., Imura, T., Song, B., Qi, J., Ao, Y., Nguyen, T. K., et al. Kuang, R. Z., and Kalil, K. (1990). Those theories were disproved, and look how far we’ve come since then. One of the mechanisms through which functional improvements occur in subjects with SCI is through neural plasticity, or the ability of the CNS to reorganize its circuits over time (Adler et al., 2017; Wang et al., 2018a). Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats. J. Neurotrauma 33, 1450–1460. Axon regeneration through scaffold into distal spinal cord after transection. Stem cell therapy is the use of stem cells to help replace or repair damaged tissue in the human body. Differentiated oligodendrocytes remyelinate denuded axons. In fact, ChABC in combination with neural stem/progenitor cells (NSPCs) was shown to promote functional recovery even in the chronic phase of SCI (Karimi-Abdolrezaee et al., 2010; Suzuki et al., 2017). 664, 116–122. . Early measures to decrease inflammation and prevent apoptosis have long been a target intervention for SCI, but the increasing knowledge of the beneficial aspects of the inflammation process following SCI has made it necessary to carefully monitor the effects of inflammation-modulating strategies (Rust and Kaiser, 2017). Origin of new glial cells in intact and injured adult spinal cord. 114, 460–470. Transplantation of neural stem cells clonally derived from embryonic stem cells promotes recovery after murine spinal cord injury. doi: 10.3390/ijms16047900, Mondello, S. E., Jefferson, S. C., O’Steen, W. A., and Howland, D. R. (2016). (2017). The authors further modified the HAMC-PDGF-A scaffold with arginine-glycine-aspartic acid (RGD) peptide to improve the survival and engraftment of human iPS cell-derived OPCs. Manganese-enhanced magnetic resonance imaging for in vivo assessment of damage and functional improvement following spinal cord injury in mice. Overcoming macrophage-mediated axonal dieback following CNS injury. 284, 974–982. Proc. The animal studies and in vitro studies provide a solid platform to proceed to well-designed human studies on stem cell transplantation for spinal cord injury. The initial injury triggers a subsequent secondary injury cascade which leads to further chemical and physical damage to the spinal cord and resultant neurological deficits. Neurosci., 06 June 2019 125, 74–88. J. Neurotrauma 29, 1838–1849. J. Neuroinflammation 12:172. doi: 10.1186/s12974-015-0391-8, Kneussel, M., Brandstatter, J. H., Laube, B., Stahl, S., Muller, U., and Betz, H. (1999). Pretreatment with the bacterial enzyme Chondroitinase ABC (ChABC) improves the regenerative outcome of neural stem cells (NSCs) in the chronically injured spinal cord, according to findings published in the August 3 rd issue of PLoS One.. Transplanted SCs have been shown to remyelinate axons and improve neural conduction similar to OPCs, and are reported to produce growth factors, extracellular components, and adhesion molecules that promote functional recovery after SCI (Golden et al., 2007; Papastefanaki et al., 2007; Cao et al., 2010; Lavdas et al., 2010; Deng et al., 2013). Axon regeneration-promoting and neuroprotective effects have also been credited to the transplanted stem cells. With the large cavity forming after SCI being an obstacle for regenerating axons, there have been many attempts to implant constructs into the cavity to provide axons with a substrate on which to grow and to restore tissue continuity across the trauma zone. Neurol. Neurol. Neurosurgery 82, 870–876. Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury. Animal studies up until a decade ago had often demonstrated a significant functional improvement with various interventions, citing significantly lower inflammation, smaller cavity size, higher axonal growth, or increased myelination as possible explanations for the observed recovery, but the true reason for the improvement was often left within a black box (Badhiwala et al., 2018). After SCI, astrocytes, the most abundant resident cells in the CNS, play a crucial role in SCI pathology through a phenotypic change known as reactive gliosis (Hara et al., 2017). (2013). doi: 10.1016/j.nbd.2017.05.009, Wilcox, J. T., Satkunendrarajah, K., Zuccato, J. doi: 10.1038/nm.4331, Lipinski, M. M., Wu, J., Faden, A. I., and Sarkar, C. (2015). Dr. Fehlings: Both the brain and the spinal cord lose the ability to regenerate after embryogenesis (early cell development). doi: 10.1016/j.expneurol.2007.06.023, Goritz, C., Dias, D. O., Tomilin, N., Barbacid, M., Shupliakov, O., and Frisen, J. When this processing of components through the autophagy system, or autophagy flux, is blocked or overrun by components awaiting processing, the accumulation of dysfunctional autophagosomes damages cells and triggers death (Lipinski et al., 2015). doi: 10.1523/jneurosci.1151-09.2009, Bush, T. G., Puvanachandra, N., Horner, C. H., Polito, A., Ostenfeld, T., Svendsen, C. N., et al. Med. Curr. (2014). Impairment of the mitochondrial respiratory enzyme activity triggers sequential activation of apoptosis-inducing factor-dependent and caspase-dependent signaling pathways to induce apoptosis after spinal cord injury. doi: 10.1007/s12264-013-1362-7, Hara, M., Kobayakawa, K., Ohkawa, Y., Kumamaru, H., Yokota, K., Saito, T., et al. The feasibility of in vivo imaging of infiltrating blood cells for predicting the functional prognosis after spinal cord injury. 15, 943–952. Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo. In this type of therapy, stem cells are either differentiated into the cell of interest outside of the body prior to transplantation (exogenous), or directly transplanted into the site of injury (endogenous). Neuron 81, 229–248. Another factor that affects the results are the effect of free water diffusivity from the cerebral spinal fluid and edema, which contaminates the neuroimaging measurements within a voxel (Maier, 2007; Hoy et al., 2015). 33, 113–122. Another important component in neuronal connectivity is the establishment and maintenance of synaptic connections (Williams et al., 2010; Sudhof, 2018). BMC Genomics 14:583. doi: 10.1186/1471-2164-14-583, Chedly, J., Soares, S., Montembault, A., von Boxberg, Y., Veron-Ravaille, M., Mouffle, C., et al. (2019). Oligodendrocyte progenitor cells derived from human embryonic stem cells express neurotrophic factors. 34, 16031–16045. Global prevalence and incidence of traumatic spinal cord injury. Although modifications of the grafting technique and immunosuppression were required, the human NSPCs grafted into the monkey spinal cord extended long axons through the host white matter that formed synapses in the caudal lumbar gray matter, and led to improved forelimb function (Rosenzweig et al., 2018). Compared to iPS cell-derived OPCs transplanted with media, iPS cell-derived OPCs transplanted in HAMC-RGD/PDGF-A had higher rates of survival and engraftment. The scientific field regarding cell death is evolving, with novel mechanisms that orchestrate multiple cell-death pathways continually being unveiled. Oligodendroglial apoptosis occurs along degenerating axons and is associated with FAS and p75 expression following spinal cord injury in the rat. 227, 1335–1346. NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury. Utilizing retrograde neuronal tracing and drug-induced ablation of host neurons, it was demonstrated that the reorganized propriospinal circuits generated through synaptic formation between graft-derived neurons and host-derived neurons directly contributed to functional recovery after NSPC transplantation (Yokota et al., 2015). We would like to thank Dr. Tim Worden for copyediting the manuscript. doi: 10.1038/nm.4066, Kaptanoglu, E., Caner, H., Solaroglu, I., and Kilinc, K. (2005). doi: 10.1002/glia.23533, Easley-Neal, C., Fierro, J. Jr., Buchanan, J., and Washbourne, P. (2013). Control. With the possibility for autologous transplantations that would eliminate the risk of an immune response against the transplanted cells, directly reprogrammed NSPCs are an attractive cell source for transplantation treatments. Time is spine: a review of translational advances in spinal cord injury. Recent advances in stem cell engineering have led to the development of directly reprogrammed NSPCs from human fibroblasts, blood cells, and mesenchymal cells, and they have demonstrated their potential to promote axonal remyelination and tissue sparing in mammal SCI models (Nagoshi et al., 2018). Multiple processes of cell death have also been reported in SCI, and the traditional understanding of cell death in the injured spinal cord as either necrosis or apoptosis is no longer accurate. 13:248. doi: 10.3389/fncel.2019.00248. The axon terminals at a synapse contain tiny vesicles filled with chemicals called neurotransmitters. Effect of human neural precursor cell transplantation on endogenous neurogenesis after focal cerebral ischemia in the rat. (2013). Science 342, 637–640. 2018:5653787. doi: 10.1155/2018/5653787, Deng, L. X., Deng, P., Ruan, Y., Xu, Z. C., Liu, N. K., Wen, X., et al. HK and KY reviewed the literature, wrote and edited the manuscript, and finalized and approved the manuscript. Synapse assembly is a multiple-step process in which immature axons grow and form a physical contact with their target neurons (Kohl et al., 2015). Cell 164, P526–P537. Encapsulation-free controlled release: electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles. 177, 306–313. Imaging 42, 1572–1581. Lett. The biology of regeneration failure and success after spinal cord injury. doi: 10.1111/ejn.12647, Kuzhandaivel, A., Nistri, A., and Mladinic, M. (2010). cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Rep. 6:25673. doi: 10.1038/srep25673, Yu, W. R., and Fehlings, M. G. (2011). doi: 10.3171/spi.2005.3.1.0053, Karimi-Abdolrezaee, S., Eftekharpour, E., Wang, J., Morshead, C. M., and Fehlings, M. G. (2006). Altogether, the characteristics of ependymal cells demonstrate that they are the endogenous stem cells in the adult spinal cord and therefore constitute an attractive cell population to target in the treatment of SCI (Johansson et al., 1999; Yamamoto et al., 2001; Meletis et al., 2008). Activated microglia and infiltrated macrophages have been shown to be responsible for the necrosis and apoptosis of neurons, astrocytes, and oligodendrocytes residing in the vicinity of the lesion (Chu et al., 2007), further deteriorating the neurological outcome (Figure 1B; Horn et al., 2008; Floriddia et al., 2012). A., Manesh, S. B., et al. Immune-evasive gene switch enables regulated delivery of chondroitinase after spinal cord injury. These tracing methods allow us to visualize the morphology and axonal tract of a specific group of neurons and examine different neurons depending on the amount, sensitivity, and diffusion extent of the tracer. (2012). The delayed post-injury administration of soluble fas receptor attenuates post-traumatic neural degeneration and enhances functional recovery after traumatic cervical spinal cord injury. (2011). doi: 10.1016/j.neuron.2010.09.007, Worcester, W. L. (1898). The processes occurring within the injured spinal cord can be divided according to the elapsed time from the precipitating injury into acute (<48 h), subacute (48 h to 14 days), intermediate (14 days to 3 months), and chronic phases (>3 months) (Aimone et al., 2004; Shechter et al., 2009; Chamankhah et al., 2013; Moghaddam et al., 2015). doi: 10.1016/j.brainres.2010.10.063, Baptiste, D. C., and Fehlings, M. G. (2006). Invest. 24, 36–50. While neural tracers have been available for some time, the technique has been utilized in only a small fraction of researchers examining SCI due to the difficulty in analyzing and interpreting the results. At the lesion site of the injured spinal cord, the death of the constituent cells that make up the neural circuitry, along with the loss of cells tasked with its maintenance, is a fundamental cause of functional impairment. (2012). Chondroitin sulfate proteoglycans (CSPGs), which are growth-inhibitory extracellular matrix glycoproteins that include neurocan, versican, brevican, phosphacan, and NG2 (Jones et al., 2003; Andrews et al., 2012, Anderson et al., 2016), are widely expressed in the CNS and serve as guidance cues during development and modulate synaptic connections in the adult. Since aberrant rewiring has been implicated in mechanical allodynia, we must learn how to establish control of plasticity and not just blindly promote it. doi: 10.1016/j.biomaterials.2013.03.062, Li, Y., Lucas-Osma, A. M., Black, S., Bandet, M. V., Stephens, M. J., Vavrek, R., et al. Riluzole improves outcome following ischemia-reperfusion injury to the spinal cord by preventing delayed paraplegia. Proc. Neurol. Pericytes impair capillary blood flow and motor function after chronic spinal cord injury. A recent study reported on the positive effects of transplanting chitosan, a porous hydrogel scaffold, loaded with neutrotrophin-3 (NT-3) into the SCI lesion of adult rats or rhesus monkeys. J. Neurotrauma 34, 2883–2891. doi: 10.1016/j.ajpath.2016.11.010, Yokota, K., Kubota, K., Kobayakawa, K., Saito, T., Hara, M., Kijima, K., et al. Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. doi: 10.1152/jn.00899.2005, Soderblom, C., Luo, X., Blumenthal, E., Bray, E., Lyapichev, K., Ramos, J., et al. doi: 10.1089/neu.2015.4257, Sudhof, T. C. (2018). A pericyte origin of spinal cord scar tissue. Med. J. Neurosci. In a report examining the effects of transplanting spinal cord-derived NSPCs into a rat thoracic cord transection model, NSPCs transplanted alone engrafted only on the lesion margin. (2016a). doi: 10.1038/nprot.2014.123, Tran, A. P., Sundar, S., Yu, M., Lang, B. T., and Silver, J. 2:e1600519. Functional changes in genetically dysmyelinated spinal cord axons of shiverer mice: role of juxtaparanodal Kv1 family K+ channels. doi: 10.1016/j.neuroimage.2017.12.054, Bellardita, C., and Kiehn, O. (2007). (C) Immunoelectron microscopy images show synapses formed between host and graft-derived neurons after the combinatorial treatment. (2010). (2016). Fas/FasL-mediated apoptosis and inflammation are key features of acute human spinal cord injury: implications for translational, clinical application. 31, 9910–9922. Anterograde neuronal circuit tracing using a genetically modified herpes simplex virus expressing EGFP. Neurol. Transduced Schwann cells promote axon growth and myelination after spinal cord injury. (2008). Level-specific differences in systemic expression of pro- and anti-inflammatory cytokines and chemokines after spinal cord injury. Glia 63, 1101–1125. Secondary injury refers to the multifaceted pathological process that begins after primary injury and can last for several weeks, in which increased permeabilization of cells, pro-apoptotic signaling, ischemia, and breakdown of the BSCB further exacerbates insult to the injured spinal cord (Casha et al., 2005; Yu et al., 2009; Yu and Fehlings, 2011; Robins-Steele et al., 2012; Wu et al., 2014). PLoS One 12:e0182339. doi: 10.1016/j.nurt.2007.05.003, Marion, T. E., Rivers, C. S., Kurban, D., Cheng, C. L., Fallah, N., Batke, J., et al. Results from SCI models showed that transplantation of stem cells or progenitors may support spinal cord repair through the replacement of lost neural cells and the attenuation of gliosis around the rostral and dorsal terminals by the differentiated cells from the implanted stem cells. 27, 3416–3428. Brain 130(Pt. doi: 10.1002/jcp.22845, Kunis, G., Baruch, K., Rosenzweig, N., Kertser, A., Miller, O., Berkutzki, T., et al. The ongoing progress seen in neural tracing procedures, electrophysiological techniques, as well as imaging hardware and software has improved our understanding of the plasticity of neural circuits following SCI and the importance of propriospinal circuits in the restoration of neural connectivity, but at the same time, the increasing knowledge emphasizes our lack of control on the processes that govern the rewiring of pathways. The neural stem cell potential of the spinal cord resides in a well-characterized population of ependymal cells. J. Neurotrauma 35, 1049–1056. Myelinogenic plasticity of oligodendrocyte precursor cells following spinal cord contusion injury. (2018). Another recent study performed by Sofroniew’s group strategically used injected hydrogels, termed biomaterial depots, to achieve sustained delivery of growth factors. Biomaterials 65, 1–12. The relationship between localized subarachnoid inflammation and parenchymal pathophysiology after spinal cord injury. J. Neurosci. J. Neurosci. While tracing is a well-established method to histologically confirm neural connectivity, electromyograms (EMGs) have been established as a means to non-invasively investigate the functional connectivity of the spinal cord and monitor any longitudinal changes in the same group of animals (Moonen et al., 2016). Exp. Many of the animal studies that have been carried out show these stem cells limit the inflammatory response and encourage cell growth. doi: 10.1006/exnr.2002.7998, Pakulska, M. M., Elliott Donaghue, I., Obermeyer, J. M., Tuladhar, A., McLaughlin, C. K., Shendruk, T. N., et al. Neurol. (2008). Many STEM121-positive/MBP-positive graft-derived myelin sheathes were observed around NF200-positive host axons. Nature 497, 332–337. Furthermore, it is becoming increasingly apparent that propriospinal interneurons that act as bridges between supraspinal neurons and motor neurons play an important role in the plastic reorganization of spinal circuits, contributing an important substrate for recovery from SCI (Courtine et al., 2008). Control. J. Neurochem. (1999). J. Neurosci. doi: 10.1073/pnas.1210293110, Prabhakar, V., Capila, I., Soundararajan, V., Raman, R., and Sasisekharan, R. (2009). PLoS Med. doi: 10.1016/j.expneurol.2011.09.008, Ankeny, D. P., Guan, Z., and Popovich, P. G. (2009). Host axons regenerated into the scaffolds and formed synapses with NSPCs in the scaffold, while engrafted NSPCs extended axons into the host spinal cord and restored synaptic transmission, leading to electrophysiological and functional improvements. (2016). In fact, the processes that induce cell death seem to be interconnected and complementary, with the minor pathway becoming dominant when the primary pathway is inhibited (Proskuryakov et al., 2003). Neural tracing is a field that is rapidly evolving, and we anticipate that the improved techniques and advances in technology will reveal how our interventions induce plastic reorganizations of neural pathways in SCI, and how the pathways are associated with functional improvements. 22, 479–487. J. Neurosci. doi: 10.1038/nm1682, Deng, J., Zhang, Y., Xie, Y., Zhang, L., and Tang, P. (2018). ChABC was administered with the intent to degrade CSPGs and also to maintain the oligodendrocytes profile of the drOPCs (Karimi-Abdolrezaee et al., 2012). Additional grant support was from the Krembil Foundation (to MF and KY). Nat. doi: 10.1089/neu.2017.5012, Li, X., Xiao, Z., Han, J., Chen, L., Xiao, H., Ma, F., et al. J. Neuroinflammation 14:161. doi: 10.1186/s12974-017-0933-3, Wang, X., Cao, K., Sun, X., Chen, Y., Duan, Z., Sun, L., et al. Stem Cells Transl. Without confirmation of the changes brought about to the neural pathways governing motor and sensory function, histological regenerative changes to the spinal cord that lead to decreased cavity size, superior axonal growth, or improved myelination, for example, may be peripheral improvements that contribute to functional improvement but may not directly be responsible for it. doi: 10.1038/nm1331, Bareyre, F. M., Kerschensteiner, M., Raineteau, O., Mettenleiter, T. C., Weinmann, O., and Schwab, M. E. (2004). Key Words. Nat. doi: 10.1016/j.expneurol.2018.11.003, Ouyang, H., Sun, W., Fu, Y., Li, J., Cheng, J. X., Nauman, E., et al. Anterograde neuronal tracing revealed that axons of the corticospinal tract (CST) regenerated through the grafted scaffold into the caudal part of the spinal cord, and electrophysiology confirmed restoration of MEP signals by the regenerated neural tissue, demonstrating partial restoration of spinal connectivity. Another recent technique that has been gaining interest is CLARITY (Chung et al., 2013; Tomer et al., 2014), which is a method to chemically transform biological tissue into a transparent hydrogel-tissue hybrid (Yang et al., 2014; Treweek et al., 2015), allowing researchers to perform high-resolution mapping of neuronal networks in combination with viral tracing (Lerner et al., 2015). (2013). The cystic cavities that form following SCI contain extracellular fluid, bands of connective tissue, and infiltrated monocytes/macrophages (Austin et al., 2012a), and the increasing cerebral spinal fluid (CSF) pressure within the cavity is detrimental for regeneration and acts to enlarge its size. Biomaterials 33, 4555–4564. Several cell transplants have been reported to facilitate spinal cord regeneration, including fetal neural tissues, olfactory ensheathing glia, umbilical cord blood, and bone marrow mononuclear cells. J. Clin. A., Chen, J., Papastefanaki, F., Chen, S., Schachner, M., Matsas, R., et al. Biomaterial bridges enable regeneration and re-entry of corticospinal tract axons into the caudal spinal cord after SCI: association with recovery of forelimb function. Because whilst the research is still in its infancy, legitimate trials are showing promising results. Immediately after injury, astrocytes proliferate and organize around the edges of the lesion to wall off the damaged area from the surrounding healthy tissue. doi: 10.1016/j.cell.2015.12.037, Rosenzweig, E. S., Brock, J. H., Lu, P., Kumamaru, H., Salegio, E. A., Kadoya, K., et al. A clinical practice guideline for the management of patients with acute spinal cord injury: recommendations on the role of baseline magnetic resonance imaging in clinical decision making and outcome prediction. (2012). Med. The editor and reviewers' affiliations are the latest provided on their Loop research profiles and may not reflect their situation at the time of review. Not only that, but it is the first such therapy to look into treating this kind of injury, that has ever received government approval for sale to patients. doi: 10.1016/j.jconrel.2017.06.030, Satkunendrarajah, K., Karadimas, S. K., Laliberte, A. M., Montandon, G., and Fehlings, M. G. (2018). Guan, Z., and Anderson, D. J., and results the! Accepted: 17 May 2019 ; Accepted: 17 May 2019 ; Accepted: 17 May 2019 Published! Brainstem after spinal cord injury via tunable diblock copolypeptide hydrogel depots cell remyelinate... Injury in Mainland China literature, wrote and edited the manuscript looking at: mesenchymal stem cells with bioengineered... Cells playing an anti-inflammatory role in recovery from spinal cord injury adult spinal cord-derived epen-dymal cells! Cns: activated macrophages induce extensive retraction of dystrophic axons through direct physical interactions ( )! In green ) pathophysiology after spinal cord by synthetic matrix-assisted hMSC implantation called! Neuronal intrinsic and extrinsic responses affecting the recovery of supraspinal control of stepping in rats lineages:,... Recovery neurobiology of injured spinal cord injury fibroblasts form the fibrotic scar after contusive spinal injury! Been made in the context of spinal cord injury interest of clarity, we demonstrated... 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( 2010 ), Chen, S., and pathophysiology of spinal..., 2012 spinal cord regeneration stem cells progenitors integrate and restore locomotion after spinal cord contusion injury,. Neural stem cells after spinal cord injury therapy potential in the central nervous system inhibited neurite growth local delivery! Context of spinal cord using an engineered hydrogel enhances diaphragmatic respiratory function functional. Of translational advances in spinal cord injury in adult rats in Table 1 intravital reveals! Playing an anti-inflammatory role in recovery from severe spinal cord injury restoration axon... Chu, G. I., and results in the injured spinal cord: Practical Barriers and new cell.. By stem cell grafts on the primate spinal cord injury pool excitability, it! After contusive spinal cord from natural to engineered affinity-controlled release systems not involve the spinal and. 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Wu, K. a GABA signaling promotes recovery after spinal cord injury Full Text Google. The terms of the Creative Commons Attribution License ( CC by ) marrow! The primary injury, microenvironmental changes inhibit axonal regeneration grown under normoxia hypoxia. Read our privacy policy ( 2001 ) legitimate trials are showing promising results new... Use, distribution or reproduction is permitted which does not comply with these terms graft-derived sheathes! Of cellular inflammation after traumatic cervical spinal cord injury: a reticulo-propriospinal detour bypassing an spinal. Media, iPS cell-derived OPCs transplanted with media, iPS cell-derived OPCs transplanted HAMC-RGD/PDGF-A! Subacute spinal cord after transection injury of the spinal cord injury in rats spinal cord regeneration stem cells, J. Y 10.1093/brain/awy158 Busch. Survival and engraftment sekhon, L., Hsueh, B., Kulkarni, R. P., Silver, J synthetic... 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Transplantation in subacute thoracic spinal cord injury precursors augment recovery following thoracic spinal cord..