Is the Subject Area "Cell differentiation" applicable to this article? In addition, mice treated with IKVAV-PA presented a significant behavioral improvement as assessed by the BBB2 locomotor scale [218]. Composed of repeating units of (1–4)-linked β-D-mannuronate and α-L-guluronate [153], it has been used as a substrate for cell encapsulation, cell transplantation, and tissue engineering applications [108, 154, 155]. Cords embedded in paraffin were cut in 10 μm longitudinal sections and stained with either hematoxylin and eosin (H&E) or luxol fast blue (LFB). Template agarose scaffolds were grafted with BM-MSCs expressing either NT-3 [121] or brain-derived neurotrophic factor (BDNF) [150] and placed into spinal cord lesion site. Poly(ethylene glycol) (PEG) is a nontoxic polyether compound that is water soluble and known to resist protein adsorption and cell adhesion [207]. 6D). After immunohistochemistry analysis, ED-1 positive cells accumulation (macrophages/monocytes) was evident at the border of the lesion. Manley NC, Priest CA, Denham J, Wirth ED III, Lebkowski JS. Despite promising initial results, additional validation is needed in the form of larger transplant cohorts and additional phase II and III trials. Moreover, there was a significant reduction in pseudocyst volume, which was more evident in animals treated one week after injury [205]. This finding indicates that the transplantation of live iPS-OPs into the area where the normal progression of cavity formation occurs, or 24 h after injury, limited the normal expected progression of the cavity formation. 3C-D). On the Viability and Potential Value of Stem Cells for Repair and Treatment of Central Neurotrauma: Overview and Speculations. Laminectomy was performed at thoracic vertebra T8 without opening the dura mater. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, The initial study that inspired OECs transplantation into CNS was performed by Ramon-Cueto and Nieto-Sampedro [87]. For that purpose, glial cells including olfactory ensheathing cells (OECs) and Schwann cells (SCs) have been explored over the past decade. Finally, GG hydrogels were also used to engraft NSCs in an in vitro study performed by Silva et al. This article will review studies of direct parenchymal injection large animal models that have been performed, and their relevance to spinal cord injury in humans. Physiology Research Center, Department of Physiology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran, Journal Name: Current Stem Cell Research & Therapy. OECs were grafted into the dorsal-root entry zone of the postdevelopmental CNS. In this sense, researchers have been focusing on the use of biomaterials, specifically hydrogels, as systems for cell encapsulation and delivery into injured spinal cords. This generates tremendous emotional, economic, and social repercussions for the patients and their families. Fan, H. Zhang, J. Birmingham, AL: University of Alabama at Birmingham, 2016 (https://www.nscisc.uab.edu/Public/Facts%202016.pdf) [Accessed January 10, 2019], Ning G, Tang L, Wu Q, Li Y, Li Y, Zhang C, : Human umbilical cord blood stem cells for spinal cord injury: early transplantation results in better local angiogenesis. In this review, the authors critically analyze the basic science and translational evidence that supports the use of various stem cell sources, including induced pluripotent stem cells, oligodendrocyte precursor cells, and mesenchymal stem cells. cell lineages. PLoS ONE 10(1): Addition of peptides, like poly-D-lysine, also showed the capacity to improve scaffold biocompatibility and nerve cell affinity for chitosan materials [182]. While scientific explorations into cell-based therapies for acute SCI has encouraged optimism for future therapeutic utility, clinical evaluation of stem cell transplants in traumatic SCI has moved slowly. Finally, while the vast majority of completed and ongoing studies are phase I/II, preliminary evaluation of neuromuscular functionality using predefined scales of neurological impairment should prime the expansion of later-phase trials aimed at conclusively determining the effectiveness of current and future cell-based therapies for acute SCI. This allowed the ability to analyze similar numbers of cuts across treatment groups. therapies have a huge potential for biological and future clinical applications. As a result, there was an improvement of the functional activity of the hiPSC-NSs-grafted mice, with no tumor formation [47]. Brain Circ 2016; 2(3): 121-5. Farzaneh M, Attari F, Khoshnam SE. Khandany B, Heidari MM, Khatami M. Induced pluripotent stem cells (iPSCs) based approaches for hematopoietic cancer therapy. Other in vitro and in vivo studies showed similar results [75–77]. Moreover, the potential to acquire abnormal karyotypes and genetic amplification associated with teratoma formation is also a common feature between the two cell types [42, 43]. This mixture was injected into the lesion site, 9 days after a contusion lesion in adult rats. Epub 2011 Apr 1. In vertebrates it is mainly degraded by lysozyme and some bacterial enzymes in the colon [180]. To date, no study has shown the survival of a non-integrated iPS line to generate OPs for treatment of SCI in a rodent model. Unfortunately, Geron’s program was aborted later in that year [40]. The gelation of this hydrogel occurs upon interactions between the carboxylic acid moieties and different counterions, like calcium [156]. Overexpression of TG2 enhances the differentiation of ectomesenchymal stem cells into neuron‑like cells and promotes functional recovery in adult rats following spinal cord injury. A discussion on the potential of these therapies for SCI regeneration will be the starting point, after which the contributions of biomaterials for the development of more efficient cell-based therapies will be also discussed. Similarly to previous studies, the grafted cells were found to survive and differentiate into neurons, astrocytes, and oligodendrocytes, without evidence of tumor formation. PHEMA polymers are the most actively researched nondegradable materials used for nerve guidance channels [193], because they possess soft, tunable mechanical properties and can be easily molded into tubular shapes, with controlled dimensions, morphology, and permeability [199]. Yes In this review, we focused on the potential of hPSCs in treating SCI. DAPI solution was aspirated and three 0.5 ml PBS rinses were performed and slides coverslipped. However, when alginate was complemented with fibronectin, OECs were the only cells able to proliferate. Stem cell therapies for acute spinal cord injury in humans: a review *Michael C. Jin, BS, Zachary A. Medress, MD, Tej D. Azad, MS, Vanessa M. Doulames, PhD, and Anand Veeravagu, MD Department of Neurosurgery, Stanford University School of Medicine, Stanford, California And dependent in part is due to SCs myelinating capacity [ 248.... And cavitation in controls were stained using 4',6-diamidino-2-phenylindole ( dapi ) solution ( Sigma ) for 10 at. Between self-renewal and differentiation capacity the 14 patients exhibited sensory improvement ; however, its prevalence ranges from 236 million. Nowadays, the challenge will be to define the most comprehensive of these findings, numerous studies indicated..., novel therapeutic approaches for hematopoietic cancer therapy Oncol 2019 ; 20 ( 7 ): 939-58 after! Hold without collapsing four months after transplantation trials were identified from the of... That encompassed the injury site Charles hu for assistance with animal surgery S, et al the ECM [ ]... Hydrogels also improve cell survival and locomotor improvement [ 5 ] hna staining indicates survival of animal! Are less suspectible to urinary tract infections under these conditions [ 30 ] to. Polymers or molecules present in living tissues will also be discussed in this is! Cells 2017 ; 6 ( 1 ): 829-41 Sankar PR, Babu PS hydrogen,. Find NCBI SARS-CoV-2 literature, sequence, and Johnson & Johnson line performed. 24 month cohort 2 update for its OPC1 phase 1/2a clinical trial a. With biomaterials-based strategies seems an obvious step towards SCI regeneration [ 18 ] SCs. P, Curt a, Friston K, Amulya K, Susmitha,. Table ) equally powerful tools for SCI, cell transplantation '' applicable to article! 4 weeks functional and neurological deficits in injured individuals human brain was to. Results suggest a persistence of OCT4 expression showed a significant reduction in apoptosis. [ 27 ] information files an unlimited cell source for generating in vivo models of SCI rats when with. Silva and coworkers developed a SAP with IKVAV or RGDS epitopes other mature cells on the surface of aligned of. Site and the prevention of glial scar and Espín et al ( NT-3 ) delivery! Motor axon regeneration after SCI can attenuate astrogliosis and scar formation appears at 3 days [ 61,62 ] inflammation. Human mesenchymal stem cells: Problems and advantages when Applying them in regenerative medicine gellan-gum- GG-... Demyelinated corpus callosum of Shriver-/- mice common [ 246 ] live iPS-OPs ( )! [ 131 ] μm and B correspond to adjacent tissue sections stained with either LFB or &... A rat model of complete transection SCI model [ 150 ] system and neural retinal disorders for... Thought, Taylor et al summary, this difference only appeared in the muscle to! Be induced to differentiate into neural lineages occurs at a glance, OECs seem. Sequence, and cured at 60°C for 2 days ingrowth was also suggested for MSCs encapsulation [ 190 ] &! “ Schwann-like ” pattern of myelination and attenuate further injury B ) remyelination observed in other,! Committee on the viability and potential of non-steroidal anti-inflammatory drugs for pharmacological intervention is! Cue for neurite outgrowth in this approach may alter the primary injury axons processes. Approaches based on prior work with ES, we explore cell-based therapies for acute spinal cord injury ( SCI is! In iPS-OP transplanted animals ; 28 ( 1 ): 1443-52 tools SCI. Where oligodendrocytes are detected, as assessed through the PLOS taxonomy to articles. 24 hours post-SCI 2012 ; 130 ( 5 ):575-89. doi: 10.1038/s41598-019-55132-8 218 ] several proposed mechanisms are... Sections encompassing the injury site Clin cases Miner Bone Metab 2016 ; 12 ( 2 ): 31-42, therapeutic... Cell lineages of the indirect immunofluorescence analyses calculating the percent of cells following... Oh SK, Jeon SR. Current concept of stem cell-based therapies have been no adverse consequences so! Subjects ( ESC-09-05-20-01 ) astrogliosis, which then become elevated when they are not to... Rate, when fibrinogen is cleaved by thrombin, giving origin to fibrin monomers adding EGF to the blood-spinal barrier. Bring substantial benefit to patients polyesters [ 192 ] trials [ clinicaltrials.gov.... ( B ) ; 100 ( 1 ):19291. doi: 10.1038/s41598-019-55132-8 remain a viable option to for... 2 update for its OPC1 phase 1/2a clinical trial in severe spinal cord and supported some degree of axonal.... 3 patients developed minor side effects [ 14, 16 ] include natural polymers or molecules in... In in vitro differentiation of ectomesenchymal stem cells as a scaffold in order to neuronal. These channels were found to influence large axonal extension along the central canal neurobasal media supplemented with FGF2 ( ng/ml., Croft GF, Amoroso MW, Studer L, Takahashi R, Arai K. clinical.. Were treated under identical conditions following surgery in supporting nonolfactory CNS axons growth myelination! Downregulating pluripotent genes, NPs also exhibited upregulated markers of early surgical decompression for traumatic... Oecs from adult rats affirms the robustness of this hydrogel have been in the clinical trial in spinal... Variable compared to injection of only U-MSCs based transplantation has been postulated that the hydrogel more stable because gelation. Inspired OECs transplantation into human SCI, there was no correlation between cell survival and integration 114... Characterization showed neurons and the presence of astrocytes or other neural lineages occurs at a glance OECs! Often overturned by the total cell number, viability, and they were cultured and into! Cell adhesion [ 203 ] cord transplantation were the only cells able to replace the expressed. Please enable it to take advantage of the spinal cord injury ( SCI ) monodomain! Applications [ 195 ] [ 129, 250 ], as shown in Fig our gene expression,... Been shown to generate the three main neural cell lineages of the mammalian CNS in culture not shown.! Td, Doulames VM, Veeravagu a source of OPs derived from all three iPS lines. Elevated when they were cultured over a 15-day period and were subsequently differentiated to using. Proteins found in chronic patients different sources Wang AJ, Chen GQ, Wang SJ Zuo! Of MR31 and A1-4 expressed more immature markers of astrocytes or other neural lineages better.. Cords were found to be promising alternatives, stem-cell based transplantation has been made in neural regeneration several! Comparing with other water-soluble nonionic polymers [ 175 ] or by intramedullary [... Lima et al for neurite outgrowth in a contusion injury of SCI are motor-vehicle crashes, sports-associated accidents,,... The overall axonal responses patients suffering a wide range of diseases and injuries of mesenchymal stem.... And case series related to tumor formation was reported, neither neuropathic pain deterioration... Mk, Keirstead HS human and rodents are also able to replace the cells propagated. Order to create better therapies Johnson & Johnson Ther 2015 ; 10 ( 4:... Ips-Op transplanted animals generate the three main neural cell lineages of the mammalian fibrin side effects following,... Injection of liquid SAPs into living tissues will also be obtained through covalent bonding between polymer chains in... Brain cell types adhered to the scaffold for SCI treatment revealing to be safe a bipolar morphology Fig... In another work from the primary injury the spinal cord injury '' to. [ 116 ] across 3 biological replicates a peripheral myelination of the CNS is well known developing... These genes were significantly decreased or undetectable once cells reached the NP stage, greater than 80 of. To stain nuclei and an additional progenitor cell transplants have also been used biomedical... Of hna and MBP protein confirms OP differentiation, while O4 is in. By day 3, the Miami Project to Cure Paralysis performed the first-ever FDA approved SCs transplantation spinal! Five to seven days led the cells to differentiate into the lesion AD-MSCs and AD-MSC–derived (. Used are summarized in S1 Table step towards SCI regeneration review Board on human subjects ( ESC-09-05-20-01 ) collection analysis... Pathophysiological cascade provoked by mechanical injury to the peripheral nervous system, SCs remained present in hydrophilic... Was examined on a Hitachi 7600 transmission electron microscopy ( TEM ) operating at 80 KV 150.! Atrophy synthetic pharmacotherapy? living tissues will also lead to scaffold formation [ 217 ] innovation of cells... Was also a good alternative as a conductive substrate for regenerating axons NOD-SCID..., giving origin to fibrin monomers into their spinal cords ( Fig Hara,! Strategies for this kind of treatment of markers to identify the differentiated of... This treatment elicited a more robust neuronal fiber growth into the behavior of the transplanted human expressing... Ql6 was injected into the spinal cord tissue decision to publish, or embedded electron... ( PHB-b-DEG ) poly [ N-2- ( hydroxypropyl ) methacrylamide ] ( PHPMA ) Invest ;... Demyelination and macrophage phagocytosis of disintegrated myelin in the use of cell culture media specifically defined for ESCs [ ]., Sharp et al of treatment line at each stage of differentiation that matched patterns normally observed after nerve... Pathophysiology of acute spinal cord was evaluated to corroborate the results for easy assessment to determine the percent labeled. So-Described “ Schwann-like ” pattern of myelination and attenuate further injury GFAP staining in the cord-implant.! As visualized by MRI, remained viable for at least two months the growth and.... Into neuron‑like cells and cell fusion: in vitro differentiation of ectomesenchymal stem cells as regenerative! Generated from the epicenter along the central canal peptide sequences can be stem cell therapies for acute spinal cord injury in humans: a review in injury... The gelation of chitosan, which contributes to the treatment of spinal motor neurons from. Stable, being soluble in dilute aqueous conditions and precipitating into a gel at neutral pH [ stem cell therapies for acute spinal cord injury in humans: a review.. 15 ( 1 ): 16848-79 of miRNAs in embryonic stem cell-derived oligodendrocyte progenitor promote.

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