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Vafaei-Nezhad S, Pour Hassan M, Noroozian M, Aliaghaei A, Shirazi Tehrani A, Abbaszadeh HA, Khoshsirat S. A Review of Low-Level Laser Therapy for Spinal Cord Injury: Challenges And Safety. J Lasers Med Sci 2020; 11:363-368. [PMID: 33425285 DOI: 10.34172/jlms.2020.59] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Introduction: Damage to the spinal cord is a central nervous system disorder that results in direct damage to neural cells (axons, cell bodies) and glia, followed by autonomic, motor and sensory impairments. Inflammatory response after this injury can contribute to secondary tissue damage that leads to further behavioral and functional disorders. Inflammation is a complex process, which occurs after an injury. If this progressive process is not well controlled can lead to additional damage to the spinal cord which is preventing neural improvement and regeneration and, which ultimately will not provide good clinical consequences. Inflammation in the injured spinal cord is a physiological response that causes the death of glial and neuronal cells. The reduction of the initial inflammatory process after damage to the spinal cord is one of the important therapeutic strategies. It has been proposed that low-level laser (LLL) therapy, as a noninvasive manner, can modulate inflammatory processes, which leads to a significant improvement in neurological symptoms after spinal cord injury (SCI). Methods: A comprehensive review was performed on SCI, the etiologies, and treatment methods using the keywords spinal cord injury, low-level laser, and inflammation in valid medical databases such as Google Scholar, PubMed, and Elsevier (76 articles). Among the collected papers, articles that were most relevant to the purposes of the study were selected and studied. Results: LLL therapy was able to reduce inflammation and also attenuate neuronal damage after spinal cord damage. Conclusion: The present study illustrates that LLL therapy has positive effects on improving functional recovery and regulating the inflammatory function in the SCI.
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Affiliation(s)
- Saeed Vafaei-Nezhad
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahnaz Pour Hassan
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohsen Noroozian
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Aliaghaei
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atefeh Shirazi Tehrani
- Faculty of Paramedical Science, Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hojjat Allah Abbaszadeh
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahrokh Khoshsirat
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Wang X, Li B, Wang Z, Wang F, Liang J, Chen C, Zhao L, Zhou B, Guo X, Ren L, Yuan X, Chen X, Wang T. miR-30b Promotes spinal cord sensory function recovery via the Sema3A/NRP-1/PlexinA1/RhoA/ROCK Pathway. J Cell Mol Med 2020; 24:12285-12297. [PMID: 32977360 PMCID: PMC7686968 DOI: 10.1111/jcmm.15591] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Revised: 06/11/2020] [Accepted: 06/16/2020] [Indexed: 12/11/2022] Open
Abstract
Spinal cord injury (SCI) induces both motor and sensory dysfunctions. We wondered whether miR-30b could promote primary sensory neuron (PSN) axon growth in inhibitory microenvironment. The neurite growth was promoted by miR-30b agomir and inhibited by antagomir. MiR-30b targeted and degraded sema3A mRNA. MiR-30b regulated the formation of sema3A-NRP-1-PlexinA1 complex via targeting sema3A. The neurite length was induced by the miR-30b agomir, and the application of sema3A protein could reverse the effect of agomir. GTP-RhoA and ROCK expression were down-regulated by miR-30b. Neurite outgrowth that inhibited by sema3A and the miR-30b antagomir was increased by Y-27632. Agomir promoted neurite growth in NogoA inhibitory conditions, which indicated miR-30b could both enhance neuronal intrinsic regenerative ability and promote neurite growth against inhibitory microenvironment via Sema3A/NRP-1/PlexinA1/RhoA/ROCK axis. The agomir could also regulate Sema3A/NRP-1/PlexinA1/RhoA/ROCK axis in vivo and restore spinal cord sensory conductive function. In conclusion, miR-30b could be a novel target for sensation recovery after SCI.
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Affiliation(s)
- Xin Wang
- Chengde Medical University, Chengde, China
| | - Bo Li
- Department of Orthopedics, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Zhijie Wang
- Department of Pediatric Internal Medicine, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Fengyan Wang
- Department of Orthopedics, 981st Hospital of the Chinese People's Liberation Army Joint Logistics Support Force, Chengde, China
| | - Jing Liang
- Department of Nursing, 981st Hospital of the Chinese People's Liberation Army Joint Logistics Support Force, Chengde, China
| | - Chuanjie Chen
- Department of Orthopedics, Chengde Central Hospital, Chengde, China
| | - Lei Zhao
- Department of Education, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Bo Zhou
- Chengde Medical University, Chengde, China.,Department of Neurology, 981st Hospital of the Chinese People's Liberation Army Joint Logistics Support Force, Chengde, China
| | - Xiaoling Guo
- Department of Neurology, 981st Hospital of the Chinese People's Liberation Army Joint Logistics Support Force, Chengde, China
| | - Liqun Ren
- Laboratory of Spinal Cord Injury and Rehabilitation, Chengde Medical University, Chengde, China
| | - Xin Yuan
- Department of Spine Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Xueming Chen
- Department of Spine Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Tianyi Wang
- Department of Orthopedics, 981st Hospital of the Chinese People's Liberation Army Joint Logistics Support Force, Chengde, China
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Gao K, He S, Kumar P, Farmer D, Zhou J, Wang A. Clonal isolation of endothelial colony-forming cells from early gestation chorionic villi of human placenta for fetal tissue regeneration. World J Stem Cells 2020; 12:123-138. [PMID: 32184937 PMCID: PMC7062038 DOI: 10.4252/wjsc.v12.i2.123] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 12/03/2019] [Accepted: 12/23/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Endothelial colony-forming cells (ECFCs) have been implicated in the process of vascularization, which includes vasculogenesis and angiogenesis. Vasculogenesis is a de novo formation of blood vessels, and is an essential physiological process that occurs during embryonic development and tissue regeneration. Angiogenesis is the growth of new capillaries from pre-existing blood vessels, which is observed both prenatally and postnatally. The placenta is an organ composed of a variety of fetal-derived cells, including ECFCs, and therefore has significant potential as a source of fetal ECFCs for tissue engineering. AIM To investigate the possibility of isolating clonal ECFCs from human early gestation chorionic villi (CV-ECFCs) of the placenta, and assess their potential for tissue engineering. METHODS The early gestation chorionic villus tissue was dissociated by enzyme digestion. Cells expressing CD31 were selected using magnetic-activated cell sorting, and plated in endothelial-specific growth medium. After 2-3 wks in culture, colonies displaying cobblestone-like morphology were manually picked using cloning cylinders. We characterized CV-ECFCs by flow cytometry, immunophenotyping, tube formation assay, and Dil-Ac-LDL uptake assay. Viral transduction of CV-ECFCs was performed using a Luciferase/tdTomato-containing lentiviral vector, and transduction efficiency was tested by fluorescent microscopy and flow cytometry. Compatibility of CV-ECFCs with a delivery vehicle was determined using an FDA approved, small intestinal submucosa extracellular matrix scaffold. RESULTS After four passages in 6-8 wks of culture, we obtained a total number of 1.8 × 107 CV-ECFCs using 100 mg of early gestational chorionic villus tissue. Immunophenotypic analyses by flow cytometry demonstrated that CV-ECFCs highly expressed the endothelial markers CD31, CD144, CD146, CD105, CD309, only partially expressed CD34, and did not express CD45 and CD90. CV-ECFCs were capable of acetylated low-density lipoprotein uptake and tube formation, similar to cord blood-derived ECFCs (CB-ECFCs). CV-ECFCs can be transduced with a Luciferase/tdTomato-containing lentiviral vector at a transduction efficiency of 85.1%. Seeding CV-ECFCs on a small intestinal submucosa extracellular matrix scaffold confirmed that CV-ECFCs were compatible with the biomaterial scaffold. CONCLUSION In summary, we established a magnetic sorting-assisted clonal isolation approach to derive CV-ECFCs. A substantial number of CV-ECFCs can be obtained within a short time frame, representing a promising novel source of ECFCs for fetal treatments.
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Affiliation(s)
- Kewa Gao
- Department of Burns and Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
- Surgical Bioengineering Laboratory, Department of Surgery, University of California Davis, Sacramento, CA 95817, United States
- Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, CA 95817, United States
| | - Siqi He
- Department of Burns and Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
- Surgical Bioengineering Laboratory, Department of Surgery, University of California Davis, Sacramento, CA 95817, United States
- Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, CA 95817, United States
| | - Priyadarsini Kumar
- Surgical Bioengineering Laboratory, Department of Surgery, University of California Davis, Sacramento, CA 95817, United States
- Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, CA 95817, United States
| | - Diana Farmer
- Surgical Bioengineering Laboratory, Department of Surgery, University of California Davis, Sacramento, CA 95817, United States
- Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, CA 95817, United States
| | - Jianda Zhou
- Department of Burns and Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
| | - Aijun Wang
- Surgical Bioengineering Laboratory, Department of Surgery, University of California Davis, Sacramento, CA 95817, United States
- Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, CA 95817, United States
- Department of Biomedical Engineering, University of California Davis, Davis, CA 95817, United States.
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Clark K, Zhang S, Barthe S, Kumar P, Pivetti C, Kreutzberg N, Reed C, Wang Y, Paxton Z, Farmer D, Guo F, Wang A. Placental Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Myelin Regeneration in an Animal Model of Multiple Sclerosis. Cells 2019; 8:1497. [PMID: 31771176 PMCID: PMC6952942 DOI: 10.3390/cells8121497] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 11/16/2019] [Accepted: 11/19/2019] [Indexed: 02/04/2023] Open
Abstract
Mesenchymal stem/stromal cells (MSCs) display potent immunomodulatory and regenerative capabilities through the secretion of bioactive factors, such as proteins, cytokines, chemokines as well as the release of extracellular vesicles (EVs). These functional properties of MSCs make them ideal candidates for the treatment of degenerative and inflammatory diseases, including multiple sclerosis (MS). MS is a heterogenous disease that is typically characterized by inflammation, demyelination, gliosis and axonal loss. In the current study, an induced experimental autoimmune encephalomyelitis (EAE) murine model of MS was utilized. At peak disease onset, animals were treated with saline, placenta-derived MSCs (PMSCs), as well as low and high doses of PMSC-EVs. Animals treated with PMSCs and high-dose PMSC-EVs displayed improved motor function outcomes as compared to animals treated with saline. Symptom improvement by PMSCs and PMSC-EVs led to reduced DNA damage in oligodendroglia populations and increased myelination within the spinal cord of treated mice. In vitro data demonstrate that PMSC-EVs promote myelin regeneration by inducing endogenous oligodendrocyte precursor cells to differentiate into mature myelinating oligodendrocytes. These findings support that PMSCs' mechanism of action is mediated by the secretion of EVs. Therefore, PMSC-derived EVs are a feasible alternative to cellular based therapies for MS, as demonstrated in an animal model of the disease.
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Affiliation(s)
- Kaitlin Clark
- Department of Surgery, School of Medicine, University of California Davis, Sacramento, CA 95817, USA; (K.C.); (S.B.); (P.K.); (C.P.); (N.K.); (C.R.); (Z.P.); (D.F.)
- Shriner’s Hospitals for Children, Northern California, Sacramento, CA 95817, USA; (S.Z.); (Y.W.); (F.G.)
| | - Sheng Zhang
- Shriner’s Hospitals for Children, Northern California, Sacramento, CA 95817, USA; (S.Z.); (Y.W.); (F.G.)
| | - Sylvain Barthe
- Department of Surgery, School of Medicine, University of California Davis, Sacramento, CA 95817, USA; (K.C.); (S.B.); (P.K.); (C.P.); (N.K.); (C.R.); (Z.P.); (D.F.)
| | - Priyadarsini Kumar
- Department of Surgery, School of Medicine, University of California Davis, Sacramento, CA 95817, USA; (K.C.); (S.B.); (P.K.); (C.P.); (N.K.); (C.R.); (Z.P.); (D.F.)
- Shriner’s Hospitals for Children, Northern California, Sacramento, CA 95817, USA; (S.Z.); (Y.W.); (F.G.)
| | - Christopher Pivetti
- Department of Surgery, School of Medicine, University of California Davis, Sacramento, CA 95817, USA; (K.C.); (S.B.); (P.K.); (C.P.); (N.K.); (C.R.); (Z.P.); (D.F.)
- Shriner’s Hospitals for Children, Northern California, Sacramento, CA 95817, USA; (S.Z.); (Y.W.); (F.G.)
| | - Nicole Kreutzberg
- Department of Surgery, School of Medicine, University of California Davis, Sacramento, CA 95817, USA; (K.C.); (S.B.); (P.K.); (C.P.); (N.K.); (C.R.); (Z.P.); (D.F.)
| | - Camille Reed
- Department of Surgery, School of Medicine, University of California Davis, Sacramento, CA 95817, USA; (K.C.); (S.B.); (P.K.); (C.P.); (N.K.); (C.R.); (Z.P.); (D.F.)
| | - Yan Wang
- Shriner’s Hospitals for Children, Northern California, Sacramento, CA 95817, USA; (S.Z.); (Y.W.); (F.G.)
| | - Zachary Paxton
- Department of Surgery, School of Medicine, University of California Davis, Sacramento, CA 95817, USA; (K.C.); (S.B.); (P.K.); (C.P.); (N.K.); (C.R.); (Z.P.); (D.F.)
| | - Diana Farmer
- Department of Surgery, School of Medicine, University of California Davis, Sacramento, CA 95817, USA; (K.C.); (S.B.); (P.K.); (C.P.); (N.K.); (C.R.); (Z.P.); (D.F.)
- Shriner’s Hospitals for Children, Northern California, Sacramento, CA 95817, USA; (S.Z.); (Y.W.); (F.G.)
| | - Fuzheng Guo
- Shriner’s Hospitals for Children, Northern California, Sacramento, CA 95817, USA; (S.Z.); (Y.W.); (F.G.)
| | - Aijun Wang
- Department of Surgery, School of Medicine, University of California Davis, Sacramento, CA 95817, USA; (K.C.); (S.B.); (P.K.); (C.P.); (N.K.); (C.R.); (Z.P.); (D.F.)
- Shriner’s Hospitals for Children, Northern California, Sacramento, CA 95817, USA; (S.Z.); (Y.W.); (F.G.)
- Department of Biomedical Engineering, University of California Davis, Davis, CA 95616, USA
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Wang T, Li B, Wang Z, Wang X, Xia Z, Ning G, Wang X, Zhang Y, Cui L, Yu M, Zhang L, Zhang Z, Yuan W, Guo X, Yuan X, Feng S, Chen X. Sorafenib promotes sensory conduction function recovery via miR-142-3p/AC9/cAMP axis post dorsal column injury. Neuropharmacology 2019; 148:347-357. [PMID: 30710569 DOI: 10.1016/j.neuropharm.2019.01.031] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2018] [Revised: 01/28/2019] [Accepted: 01/29/2019] [Indexed: 02/07/2023]
Abstract
Spinal cord injury results in sensation dysfunction. This study explored miR-142-3p, which acts a critical role in sciatic nerve conditioning injury (SNCI) promoting the repair of the dorsal column injury and validated its function on primary sensory neuron(DRG). miR-142-3p expression increased greatly in the spinal cord dorsal column lesion (SDCL) group and increased slightly in the SNCI group. Subsequently, the expression of adenylate cyclase 9 (AC9), the target gene of miR-142-3p, declined sharply in the SDCL group and declined limitedly in the SNCI group. The expression trend of cAMP was opposite to that of miR-142-3p. MiR-142-3p inhibitor improved the axon length, upregulated the expression of AC9, cAMP, p-CREB, IL-6, and GAP43, and downregulated the expression of GTP-RhoA. miR-142-3p inhibitor combined with AC9 siRNA showed shorter axon length, the expression of AC9, cAMP, p-CREB, IL-6, and GAP43 was decreased, and the expression of GTP-RhoA was increased. H89 and AG490, inhibitors of cAMP/PKA pathway and IL6/STAT3/GAP43 axis, respectively, declined the enhanced axonal growth by miR-142-3p inhibitor and altered the expression level of the corresponding proteins. Thus, a substitution therapy using Sorafenib that downregulates the miR-142-3p expression for SNCI was investigated. The results showed the effect of Sorafenib was similar to that of miR-142-3p inhibitor and SNCI on both axon growth in vitro and sensory conduction function recovery in vivo. In conclusion, miR-142-3p acts a pivotal role in SNCI promoting the repair of dorsal column injury. Sorafenib mimics the treatment effect of SNCI via downregulation of miR-142-3p, subsequently, promoting sensory conduction function recovery post dorsal column injury.
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Affiliation(s)
- Tianyi Wang
- Department of Orthopedics, The 981st Hospital of the Chinese People's Liberation Army, Chengde, 067000, Hebei Province, PR China
| | - Bo Li
- Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, PR China
| | - Zhijie Wang
- Department of Pediatric Internal Medicine, Affiliated Hospital of Chengde Medical University, Chengde, 067000, Hebei Province, PR China
| | - Xin Wang
- Chengde Medical University, Chengde, 067000, Hebei Province, PR China
| | - Ziwei Xia
- Department of Orthopedics, The Second Hospital of Tianjin Medical University, Tianjin, 300211, PR China
| | - Guangzhi Ning
- Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, PR China
| | - Xu Wang
- Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, PR China
| | - Yanjun Zhang
- Department of Spine Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 100000, PR China
| | - Libin Cui
- Department of Spine Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 100000, PR China
| | - Mei Yu
- Leukemia Center, Chinese Academy of Medical Sciences & Peking Union of Medical College, Institute of Hematology & Hospital of Blood Diseases, Tianjin, 30020, PR China
| | - Liang Zhang
- Department of Orthopedics, The Second Hospital of Tianjin Medical University, Tianjin, 300211, PR China
| | - Zheng Zhang
- Department of Orthopedics, The 981st Hospital of the Chinese People's Liberation Army, Chengde, 067000, Hebei Province, PR China
| | - Wenqi Yuan
- Department of Spinal Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750000, Ningxia, PR China
| | - Xiaoling Guo
- Department of Neurology, The 981st Hospital of the Chinese People's Liberation Army, Chengde, 067000, Hebei Province, PR China.
| | - Xin Yuan
- Department of Spine Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 100000, PR China.
| | - Shiqing Feng
- Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, PR China; International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, 154 Anshan Road, Heping District, Tianjin, 300052, PR China.
| | - Xueming Chen
- Department of Spine Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 100000, PR China.
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Leng Z, Kethidi N, Chang AJ, Sun L, Zhai J, Yang Y, Xu J, He X. Muse cells and Neurorestoratology. JOURNAL OF NEURORESTORATOLOGY 2019. [DOI: 10.26599/jnr.2019.9040005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Multilineage-differentiating stress-enduring (Muse) cells were discovered in 2010 as a subpopulation of mesenchymal stroma cells (MSCs). Muse cells can self-renew and tolerate severe culturing conditions. These cells can differentiate into three lineage cells spontaneously or in induced medium but do not form teratoma in vitro or in vivo. Central nervous system (CNS) diseases, such as intracerebral hemorrhage (ICH), cerebral infarction, and spinal cord injury are normally disastrous. Despite numerous therapy strategies, CNS diseases are difficult to recover. As a novel kind of pluripotent stem cells, Muse cells have shown great regeneration capacity in many animal models, including acute myocardial infarction, hepatectomy, and acute cerebral ischemia (ACI). After injection into injury sites, Muse cells survived, migrated, and differentiated into functional neurons with synaptic junctions to local neurons and contributed to recovery of function. Furthermore, Muse cell differentiation did not need to be induced pre-transplantation and no tumors were observed post- transplantation. The Muse cell population is promising and may lead to a revolution in regenerative medicine. This review focuses on recent advances regarding the Muse cells therapies in Neurorestoratology and discusses future perspectives in this field.
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