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Shen YJ, Huang YC, Cheng YC. Advancements in Antioxidant-Based Therapeutics for Spinal Cord Injury: A Critical Review of Strategies and Combination Approaches. Antioxidants (Basel) 2024; 14:17. [PMID: 39857350 PMCID: PMC11763222 DOI: 10.3390/antiox14010017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Revised: 12/21/2024] [Accepted: 12/24/2024] [Indexed: 01/27/2025] Open
Abstract
Spinal cord injury (SCI) initiates a cascade of secondary damage driven by oxidative stress, characterized by the excessive production of reactive oxygen species and other reactive molecules, which exacerbate cellular and tissue damage through the activation of deleterious signaling pathways. This review provides a comprehensive and critical evaluation of recent advancements in antioxidant-based therapeutic strategies for SCI, including natural compounds, RNA-based therapies, stem cell interventions, and biomaterial applications. It emphasizes the limitations of single-regimen approaches, particularly their limited efficacy and suboptimal delivery to injured spinal cord tissue, while highlighting the synergistic potential of combination therapies that integrate multiple modalities to address the multifaceted pathophysiology of SCI. By analyzing emerging trends and current limitations, this review identifies key challenges and proposes future directions, including the refinement of antioxidant delivery systems, the development of multi-targeted approaches, and strategies to overcome the structural complexities of the spinal cord. This work underscores the pressing need for innovative and integrative therapeutic approaches to advance the clinical translation of antioxidant-based interventions and improve outcomes for SCI patients.
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Affiliation(s)
- Yang-Jin Shen
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
| | - Yin-Cheng Huang
- Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan 333423, Taiwan
- Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou Medical Center, Taoyuan 333423, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
| | - Yi-Chuan Cheng
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
- Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan 333423, Taiwan
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Zeng CW. Advancing Spinal Cord Injury Treatment through Stem Cell Therapy: A Comprehensive Review of Cell Types, Challenges, and Emerging Technologies in Regenerative Medicine. Int J Mol Sci 2023; 24:14349. [PMID: 37762654 PMCID: PMC10532158 DOI: 10.3390/ijms241814349] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 09/17/2023] [Accepted: 09/19/2023] [Indexed: 09/29/2023] Open
Abstract
Spinal cord injuries (SCIs) can lead to significant neurological deficits and lifelong disability, with far-reaching physical, psychological, and economic consequences for affected individuals and their families. Current treatments for SCIs are limited in their ability to restore function, and there is a pressing need for innovative therapeutic approaches. Stem cell therapy has emerged as a promising strategy to promote the regeneration and repair of damaged neural tissue following SCIs. This review article comprehensively discusses the potential of different stem cell types, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and neural stem/progenitor cells (NSPCs), in SCI treatment. We provide an in-depth analysis of the unique advantages and challenges associated with each stem cell type, as well as the latest advancements in the field. Furthermore, we address the critical challenges faced in stem cell therapy for SCIs, including safety concerns, ethical considerations, standardization of protocols, optimization of transplantation parameters, and the development of effective outcome measures. We also discuss the integration of novel technologies such as gene editing, biomaterials, and tissue engineering to enhance the therapeutic potential of stem cells. The article concludes by emphasizing the importance of collaborative efforts among various stakeholders in the scientific community, including researchers, clinicians, bioengineers, industry partners, and patients, to overcome these challenges and realize the full potential of stem cell therapy for SCI patients. By fostering such collaborations and advancing our understanding of stem cell biology and regenerative medicine, we can pave the way for the development of groundbreaking therapies that improve the lives of those affected by SCIs.
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Affiliation(s)
- Chih-Wei Zeng
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;
- Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Stepanova OV, Fursa GA, Andretsova SS, Shishkina VS, Voronova AD, Chadin AV, Karsuntseva EK, Reshetov IV, Chekhonin VP. Prospects for the use of olfactory mucosa cells in bioprinting for the treatment of spinal cord injuries. World J Clin Cases 2023; 11:322-331. [PMID: 36686356 PMCID: PMC9850961 DOI: 10.12998/wjcc.v11.i2.322] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 11/28/2022] [Accepted: 01/05/2023] [Indexed: 01/12/2023] Open
Abstract
The review focuses on the most important areas of cell therapy for spinal cord injuries. Olfactory mucosa cells are promising for transplantation. Obtaining these cells is safe for patients. The use of olfactory mucosa cells is effective in restoring motor function due to the remyelination and regeneration of axons after spinal cord injuries. These cells express neurotrophic factors that play an important role in the functional recovery of nerve tissue after spinal cord injuries. In addition, it is possible to increase the content of neurotrophic factors, at the site of injury, exogenously by the direct injection of neurotrophic factors or their delivery using gene therapy. The advantages of olfactory mucosa cells, in combination with neurotrophic factors, open up wide possibilities for their application in three-dimensional and four-dimensional bioprinting technology treating spinal cord injuries.
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Affiliation(s)
- Olga Vladislavovna Stepanova
- Department of Basic and Applied Neurobiology, V.P. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia
- Department of Neurohumoral and Immunological Research, National Medical Research Center of Cardiology, Moscow 121552, Russia
| | - Grigorii Andreevich Fursa
- Department of Basic and Applied Neurobiology, V.P. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia
| | - Svetlana Sergeevna Andretsova
- Department of Basic and Applied Neurobiology, V.P. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia
- Department of Biology, Moscow State University, Moscow 119991, Russia
| | - Valentina Sergeevna Shishkina
- Department of Basic and Applied Neurobiology, V.P. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia
| | - Anastasia Denisovna Voronova
- Department of Basic and Applied Neurobiology, V.P. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia
| | - Andrey Viktorovich Chadin
- Department of Basic and Applied Neurobiology, V.P. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia
| | | | | | - Vladimir Pavlovich Chekhonin
- Department of Basic and Applied Neurobiology, V.P. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia
- Department of Medical Nanobiotechnologу, N.I. Pirogov Russian National Research Medical University, Moscow 117997, Russia
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Cell–Cell Contact Mediates Gene Expression and Fate Choice of Human Neural Stem/Progenitor Cells. Cells 2022; 11:cells11111741. [PMID: 35681435 PMCID: PMC9179342 DOI: 10.3390/cells11111741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 04/21/2022] [Accepted: 05/12/2022] [Indexed: 02/04/2023] Open
Abstract
Transplantation of Neural Stem/Progenitor Cells (NPCs) is a promising regenerative strategy to promote neural repair following injury and degeneration because of the ability of these cells to proliferate, migrate, and integrate with the host tissue. Precise in vitro control of NPC proliferation without compromising multipotency and differentiation ability is critical in stem cell maintenance. This idea was highlighted in recent clinical trials, where discrepancies in NPC culturing protocols produced inconsistent therapeutic benefits. Of note, cell density plays an important role in regulating the survival, proliferation, differentiation, and fate choice of stem cells. To determine the extent of variability produced by inconsistent culturing densities, the present study cultured human-induced pluripotent NPCs (hiPSC-NPCs) at either a low or high plating density. hiPSC-NPCs were then isolated for transcriptomic analysis or differentiation in vitro. Following sequencing analysis, genes involved in cell–cell contact-mediated pathways, including Hippo-signaling, NOTCH, and WNT were differentially expressed. Modulation of these pathways was highly associated with the regulation of pro-neuronal transcription factors, which were also upregulated in response to higher-density hiPSC-NPC culture. Moreover, higher plating density translated into a greater neuronal and less astrocytic differentiation in vitro. This study highlights the importance of precisely controlling culture conditions during the development of NPC transplantation therapies.
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Liu S, Xie YY, Wang LD, Tai CX, Chen D, Mu D, Cui YY, Wang B. A multi-channel collagen scaffold loaded with neural stem cells for the repair of spinal cord injury. Neural Regen Res 2021; 16:2284-2292. [PMID: 33818514 PMCID: PMC8354107 DOI: 10.4103/1673-5374.310698] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Collagen scaffolds possess a three-dimensional porous structure that provides sufficient space for cell growth and proliferation, the passage of nutrients and oxygen, and the discharge of metabolites. In this study, a porous collagen scaffold with axially-aligned luminal conduits was prepared. In vitro biocompatibility analysis of the collagen scaffold revealed that it enhances the activity of neural stem cells and promotes cell extension, without affecting cell differentiation. The collagen scaffold loaded with neural stem cells improved the hindlimb motor function in the rat model of T8 complete transection and promoted nerve regeneration. The collagen scaffold was completely degraded in vivo within 5 weeks of implantation, exhibiting good biodegradability. Rectal temperature, C-reactive protein expression and CD68 staining demonstrated that rats with spinal cord injury that underwent implantation of the collagen scaffold had no notable inflammatory reaction. These findings suggest that this novel collagen scaffold is a good carrier for neural stem cell transplantation, thereby enhancing spinal cord repair following injury. This study was approved by the Animal Ethics Committee of Nanjing Drum Tower Hospital (the Affiliated Hospital of Nanjing University Medical School), China (approval No. 2019AE02005) on June 15, 2019.
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Affiliation(s)
- Shuo Liu
- Clinical Stem Cell Center, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China
| | - Yuan-Yuan Xie
- Clinical Stem Cell Center, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China
| | - Liu-Di Wang
- Clinical Stem Cell Center, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China
| | - Chen-Xu Tai
- Clinical Stem Cell Center, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China
| | - Dong Chen
- Clinical Stem Cell Center, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China
| | - Dan Mu
- Department of Radiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China
| | - Yan-Yan Cui
- Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, China
| | - Bin Wang
- Clinical Stem Cell Center, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China
- Correspondence to: Bin Wang, .
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Zhang WJ, Luo C, Huang C, Liu SC, Luo HL. Microencapsulated Neural Stem Cells Inhibit Sciatic Nerve Injury-Induced Pain by Reducing P2 × 4 Receptor Expression. Front Cell Dev Biol 2021; 9:656780. [PMID: 34621735 PMCID: PMC8491744 DOI: 10.3389/fcell.2021.656780] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 08/09/2021] [Indexed: 11/13/2022] Open
Abstract
Objectives: The purpose of this study is to investigate the effects of transplantation of microencapsulated neural stem cells (MC-NSCs), which downregulate the P2 × 4 receptor (P2 × 4R) overexpression and relieve neuropathic pain (NPP). Methods: Neural stem cells (NSCs) and MC-NSCs were transplanted to the injured sciatic nerve. Transmission electron microscope and immunofluorescence were used to observe the changes of injured sciatic nerve. Behavioral methods were used to detect mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL) of rats. Expression levels of P2 × 4Rs and p-p65 in the spinal cord segment of rats were measured by using molecular biology methods. The concentrations of IL-1β and TNF-α were detected in serum of rats by ELISA. Results: After sciatic nerve injury, the sciatic nerve fibers had the myelinated lamina separated, and disintegrated fragments could be seen. The fluorescence intensity of myelin MBP was weakened. The MWT and TWL were significantly decreased, the expression of P2 × 4Rs and p-p65 were significantly increased, and the concentrations of IL-1β and TNF-α were increased. After NSC and MC-NSC transplantation, the myelin sheath of the sciatic nerve was relatively intact, some demyelination changes could be seen, and the injured sciatic nerve has been improved. The fluorescence intensity of myelin MBP was increased. The MWT and TWL were increased, expression levels of P2 × 4Rs and p-p65 were decreased, and the concentrations of IL-1β and TNF-α were significantly decreased. Compared with NSC transplantation, transplantation of MC-NSCs could better repair the damaged sciatic nerve, decrease the expression of P2 × 4Rs and p-p65, decrease the level of IL-1β and TNF-α, and relieve pain (all p-values < 0.05). Conclusion: NSCs and MC-NSCs transplantation may alleviate pain by reducing the expression of P2 × 4Rs and inhibiting the activation of NF-KB signaling, while MC-NSCs transplantation has a better effect of suppressing pain. Our experimental results provide new data support for the treatment of NPP.
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Affiliation(s)
| | | | | | | | - Hong-liang Luo
- The Second Affiliated Hospital, Nanchang University, Nanchang, China
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7
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Nisin and non-essential amino acids: new perspective in differentiation of neural progenitors from human-induced pluripotent stem cells in vitro. Hum Cell 2021; 34:1142-1152. [PMID: 33899160 DOI: 10.1007/s13577-021-00537-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 04/16/2021] [Indexed: 12/23/2022]
Abstract
Over the past decades, stem cell therapy has been investigated as a promising approach towards various diseases, including neurodegenerative disorders. Stem cells show the capability to differentiate into neuronal progenitor cells in vitro. In the present study, the differentiation potential of human-induced pluripotent stem cells (hiPSCs) into neural lineages was examined under the efficient induction media containing forskolin and 3-isobutyl-1-methyl-xanthine (IBMX) in the presence of nisin (Ni), non-essential amino acids (NEAA) and combination of those (NEAA-Ni) in vitro. The optimum concentrations of these factors were obtained by MTT assay and acridine orange (AO) staining. The effect of Ni and NEAA on the expression rate of neural-specific markers including NSE, MAP2, and ß-tubulin III was studied via immunocytochemistry (ICC) and real-time RT-PCR analyses. Our results indicated that the induction medium containing Ni or NEAA increased the gene and protein expression of NSE, MAP2, and β-tubulin III on the 14th differentiation day. On the other hand, NEAA-Ni showed a less-differentiated hiPSCs compared to Ni and NEAA alone. In conclusion, the obtained results illustrated that Ni and NEAA could be applied as effective factors for neural differentiation of hiPSCs in the future.
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Won JS, Yeon JY, Pyeon HJ, Noh YJ, Hwang JY, Kim CK, Nam H, Lee KH, Lee SH, Joo KM. Optimal Preclinical Conditions for Using Adult Human Multipotent Neural Cells in the Treatment of Spinal Cord Injury. Int J Mol Sci 2021; 22:ijms22052579. [PMID: 33806636 PMCID: PMC7961778 DOI: 10.3390/ijms22052579] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 02/26/2021] [Accepted: 02/27/2021] [Indexed: 01/29/2023] Open
Abstract
Stem cell-based therapeutics are amongst the most promising next-generation therapeutic approaches for the treatment of spinal cord injury (SCI), as they may promote the repair or regeneration of damaged spinal cord tissues. However, preclinical optimization should be performed before clinical application to guarantee safety and therapeutic effect. Here, we investigated the optimal injection route and dose for adult human multipotent neural cells (ahMNCs) from patients with hemorrhagic stroke using an SCI animal model. ahMNCs demonstrate several characteristics associated with neural stem cells (NSCs), including the expression of NSC-specific markers, self-renewal, and multi neural cell lineage differentiation potential. When ahMNCs were transplanted into the lateral ventricle of the SCI animal model, they specifically migrated within 24 h of injection to the damaged spinal cord, where they survived for at least 5 weeks after injection. Although ahMNC transplantation promoted significant locomotor recovery, the injection dose was shown to influence treatment outcomes, with a 1 × 106 (medium) dose of ahMNCs producing significantly better functional recovery than a 3 × 105 (low) dose. There was no significant gain in effect with the 3 × 106 ahMNCs dose. Histological analysis suggested that ahMNCs exert their effects by modulating glial scar formation, neuroprotection, and/or angiogenesis. These data indicate that ahMNCs from patients with hemorrhagic stroke could be used to develop stem cell therapies for SCI and that the indirect injection route could be clinically relevant. Moreover, the optimal transplantation dose of ahMNCs defined in this preclinical study might be helpful in calculating its optimal injection dose for patients with SCI in the future.
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Affiliation(s)
- Jeong-Seob Won
- Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea;
- Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea; (C.K.K.); (H.N.); (K.-H.L.)
- Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea;
| | - Je Young Yeon
- Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea;
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
| | - Hee-Jang Pyeon
- Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea; (H.-J.P.); (Y.-J.N.); (J.-Y.H.)
- Medical Innovation Technology Inc. (MEDINNO Inc.), Ace High-End Tower Classic 26, Seoul 08517, Korea
| | - Yu-Jeong Noh
- Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea; (H.-J.P.); (Y.-J.N.); (J.-Y.H.)
| | - Ji-Yoon Hwang
- Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea; (H.-J.P.); (Y.-J.N.); (J.-Y.H.)
- Medical Innovation Technology Inc. (MEDINNO Inc.), Ace High-End Tower Classic 26, Seoul 08517, Korea
| | - Chung Kwon Kim
- Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea; (C.K.K.); (H.N.); (K.-H.L.)
- Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea; (H.-J.P.); (Y.-J.N.); (J.-Y.H.)
- Medical Innovation Technology Inc. (MEDINNO Inc.), Ace High-End Tower Classic 26, Seoul 08517, Korea
- Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon 16419, Korea
| | - Hyun Nam
- Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea; (C.K.K.); (H.N.); (K.-H.L.)
- Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea;
- Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea; (H.-J.P.); (Y.-J.N.); (J.-Y.H.)
- Medical Innovation Technology Inc. (MEDINNO Inc.), Ace High-End Tower Classic 26, Seoul 08517, Korea
| | - Kyung-Hoon Lee
- Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea; (C.K.K.); (H.N.); (K.-H.L.)
- Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea; (H.-J.P.); (Y.-J.N.); (J.-Y.H.)
- Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon 16419, Korea
| | - Sun-Ho Lee
- Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea;
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
- Correspondence: (S.-H.L.); (K.M.J.); Tel.: +82-2-3410-2457 (S.-H.L.); +82-2-2148-9779 (K.M.J.); Fax: +82-2-3410-0048 (S.-H.L.); +82-2-2148-9829 (K.M.J.)
| | - Kyeung Min Joo
- Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea;
- Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea; (C.K.K.); (H.N.); (K.-H.L.)
- Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea;
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
- Medical Innovation Technology Inc. (MEDINNO Inc.), Ace High-End Tower Classic 26, Seoul 08517, Korea
- Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon 16419, Korea
- Correspondence: (S.-H.L.); (K.M.J.); Tel.: +82-2-3410-2457 (S.-H.L.); +82-2-2148-9779 (K.M.J.); Fax: +82-2-3410-0048 (S.-H.L.); +82-2-2148-9829 (K.M.J.)
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Ottoboni L, von Wunster B, Martino G. Therapeutic Plasticity of Neural Stem Cells. Front Neurol 2020; 11:148. [PMID: 32265815 PMCID: PMC7100551 DOI: 10.3389/fneur.2020.00148] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Accepted: 02/14/2020] [Indexed: 12/21/2022] Open
Abstract
Neural stem cells (NSCs) have garnered significant scientific and commercial interest in the last 15 years. Given their plasticity, defined as the ability to develop into different phenotypes inside and outside of the nervous system, with a capacity of almost unlimited self-renewal, of releasing trophic and immunomodulatory factors, and of exploiting temporal and spatial dynamics, NSCs have been proposed for (i) neurotoxicity testing; (ii) cellular therapies to treat CNS diseases; (iii) neural tissue engineering and repair; (iv) drug target validation and testing; (v) personalized medicine. Moreover, given the growing interest in developing cell-based therapies to target neurodegenerative diseases, recent progress in developing NSCs from human-induced pluripotent stem cells has produced an analog of endogenous NSCs. Herein, we will review the current understanding on emerging conceptual and technological topics in the neural stem cell field, such as deep characterization of the human compartment, single-cell spatial-temporal dynamics, reprogramming from somatic cells, and NSC manipulation and monitoring. Together, these aspects contribute to further disentangling NSC plasticity to better exploit the potential of those cells, which, in the future, might offer new strategies for brain therapies.
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Affiliation(s)
- Linda Ottoboni
- Neurology and Neuroimmunology Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy
| | | | - Gianvito Martino
- Neurology and Neuroimmunology Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.,Università Vita-Salute San Raffaele, School of Medicine, Milan, Italy
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