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1
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Comini G, Dowd E. A systematic review of progenitor survival and maturation in Parkinsonian models. Neural Regen Res 2025; 20:3172-3178. [PMID: 39589166 PMCID: PMC11881725 DOI: 10.4103/nrr.nrr-d-24-00894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 09/14/2024] [Accepted: 10/08/2024] [Indexed: 11/27/2024] Open
Abstract
Stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell source. Unlike current therapeutic options for patients, this approach has the potential to provide long-term stem cell-derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to patients. The ultimate clinical success of stem cell-derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian brain. Because the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies, the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease. A defined systematic search of the PubMed database was completed to identify relevant studies published up to March 2024. After screening, 76 articles were included in the analysis from which 178 separate transplant studies were identified. From these, graft survival could be assessed in 52 studies and differentiation in 129 studies. Overall, we found that graft survival ranged from < 1% to 500% of cells transplanted, with a median of 51% of transplanted cells surviving in the brain; while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%. This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.
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Affiliation(s)
- Giulia Comini
- Pharmacology & Therapeutics and Galway Neuroscience Center, University of Galway, Galway, Ireland
| | - Eilís Dowd
- Pharmacology & Therapeutics and Galway Neuroscience Center, University of Galway, Galway, Ireland
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Yi LX, Woon HR, Saw G, Zeng L, Tan EK, Zhou ZD. Induced pluripotent stem cell-related approaches to generate dopaminergic neurons for Parkinson's disease. Neural Regen Res 2025; 20:3193-3206. [PMID: 39665833 PMCID: PMC11881713 DOI: 10.4103/nrr.nrr-d-24-00771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 09/25/2024] [Accepted: 10/23/2024] [Indexed: 12/13/2024] Open
Abstract
The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease, the second most common human neurodegenerative disease. Although the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear, the advancement of stem cell approaches has shown promise for Parkinson's disease research and therapy. The induced pluripotent stem cells have been commonly used to generate dopaminergic neurons, which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease therapies. The current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem cells. The benefits of induced pluripotent stem cell-based research are highlighted. Various dopaminergic neuron differentiation protocols from induced pluripotent stem cells are compared. The emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are evaluated. Finally, limitations, challenges, and future directions of induced pluripotent stem cell-based approaches are analyzed and proposed, which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.
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Affiliation(s)
| | | | | | - Li Zeng
- National Neuroscience Institute, Singapore
- Department of Neurology, Singapore General Hospital, Singapore
- Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore
| | - Eng King Tan
- National Neuroscience Institute, Singapore
- Department of Neurology, Singapore General Hospital, Singapore
- Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore
| | - Zhi Dong Zhou
- National Neuroscience Institute, Singapore
- Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore
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Barker RA, Björklund A, Parmar M. The history and status of dopamine cell therapies for Parkinson's disease. Bioessays 2024; 46:e2400118. [PMID: 39058892 PMCID: PMC11589688 DOI: 10.1002/bies.202400118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 06/26/2024] [Accepted: 07/01/2024] [Indexed: 07/28/2024]
Abstract
Parkinson's disease (PD) is characterized by the loss of the dopaminergic nigrostriatal pathway which has led to the successful development of drug therapies that replace or stimulate this network pharmacologically. Although these drugs work well in the early stages of the disease, over time they produce side effects along with less consistent clinical benefits to the person with Parkinson's (PwP). As such there has been much interest in repairing this pathway using transplants of dopamine neurons. This work which began 50 years ago this September is still ongoing and has now moved to first in human trials using human pluripotent stem cell-derived dopaminergic neurons. The results of these trials are eagerly awaited although proof of principle data has already come from trials using human fetal midbrain dopamine cell transplants. This data has shown that developing dopamine cells when transplanted in the brain of a PwP can survive long term with clinical benefits lasting decades and with restoration of normal dopaminergic innervation in the grafted striatum. In this article, we discuss the history of this field and how this has now led us to the recent stem cell trials for PwP.
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Affiliation(s)
- Roger A. Barker
- Department of Clinical Neurosciences and Cambridge Stem Cell InstituteJohn van Geest Centre for Brain RepairUniversity of CambridgeCambridgeUK
| | - Anders Björklund
- Department of Experimental Medical ScienceWallenberg Neuroscience CenterLund UniversityLundSweden
| | - Malin Parmar
- Department of Experimental Medical ScienceWallenberg Neuroscience CenterLund UniversityLundSweden
- Department of Clinical Sciences LundLund Stem Cell Center and Division of NeurologyLund UniversityLundSweden
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Ale Y, Nainwal N. Exosomes as nanocarrier for Neurotherapy: Journey from application to challenges. J Drug Deliv Sci Technol 2024; 101:106312. [DOI: 10.1016/j.jddst.2024.106312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Park JM, Rahmati M, Lee SC, Shin JI, Kim YW. Effects of mesenchymal stem cell on dopaminergic neurons, motor and memory functions in animal models of Parkinson's disease: a systematic review and meta-analysis. Neural Regen Res 2024; 19:1584-1592. [PMID: 38051903 PMCID: PMC10883506 DOI: 10.4103/1673-5374.387976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 10/09/2023] [Indexed: 12/07/2023] Open
Abstract
ABSTRACT Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, and although restoring striatal dopamine levels may improve symptoms, no treatment can cure or reverse the disease itself. Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson's disease. Mesenchymal stem cells are considered a promising option due to fewer ethical concerns, a lower risk of immune rejection, and a lower risk of teratogenicity. We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function, memory, and preservation of dopaminergic neurons in a Parkinson's disease animal model. We searched bibliographic databases (PubMed/MEDLINE, Embase, CENTRAL, Scopus, and Web of Science) to identify articles and included only peer-reviewed in vivo interventional animal studies published in any language through June 28, 2023. The study utilized the random-effect model to estimate the 95% confidence intervals (CI) of the standard mean differences (SMD) between the treatment and control groups. We use the systematic review center for laboratory animal experimentation's risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment. A total of 33 studies with data from 840 Parkinson's disease model animals were included in the meta-analysis. Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test. Among the stem cell types, the bone marrow MSCs with neurotrophic factor group showed largest effect size (SMD [95% CI] = -6.21 [-9.50 to -2.93], P = 0.0001, I2 = 0.0 %). The stem cell treatment group had significantly more tyrosine hydroxylase positive dopaminergic neurons in the striatum ([95% CI] = 1.04 [0.59 to 1.49], P = 0.0001, I2 = 65.1 %) and substantia nigra (SMD [95% CI] = 1.38 [0.89 to 1.87], P = 0.0001, I2 = 75.3 %), indicating a protective effect on dopaminergic neurons. Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route (SMD [95% CI] = -2.59 [-3.25 to -1.94], P = 0.0001, I2 = 74.4 %). The memory test showed significant improvement only in the intravenous route (SMD [95% CI] = 4.80 [1.84 to 7.76], P = 0.027, I2 = 79.6 %). Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson's disease. Further research is required to determine the optimal stem cell types, modifications, transplanted cell numbers, and delivery methods for these protocols.
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Affiliation(s)
- Jong Mi Park
- Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Masoud Rahmati
- Department of Physical Education and Sport Sciences, Faculty of Literature and Human Sciences, Lorestan University, Khoramabad, Iran
| | - Sang Chul Lee
- Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae Il Shin
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, South Korea
| | - Yong Wook Kim
- Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, South Korea
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Bennett JI, Boit MO, Gregorio NE, Zhang F, Kibler RD, Hoye JW, Prado O, Rapp PB, Murry CE, Stevens KR, DeForest CA. Genetically Encoded XTEN-based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell Therapies. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2301708. [PMID: 38477407 PMCID: PMC11200090 DOI: 10.1002/advs.202301708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 01/08/2024] [Indexed: 03/14/2024]
Abstract
While direct cell transplantation holds great promise in treating many debilitating diseases, poor cell survival and engraftment following injection have limited effective clinical translation. Though injectable biomaterials offer protection against membrane-damaging extensional flow and supply a supportive 3D environment in vivo that ultimately improves cell retention and therapeutic costs, most are created from synthetic or naturally harvested polymers that are immunogenic and/or chemically ill-defined. This work presents a shear-thinning and self-healing telechelic recombinant protein-based hydrogel designed around XTEN - a well-expressible, non-immunogenic, and intrinsically disordered polypeptide previously evolved as a genetically encoded alternative to PEGylation to "eXTENd" the in vivo half-life of fused protein therapeutics. By flanking XTEN with self-associating coil domains derived from cartilage oligomeric matrix protein, single-component physically crosslinked hydrogels exhibiting rapid shear thinning and self-healing through homopentameric coiled-coil bundling are formed. Individual and combined point mutations that variably stabilize coil association enables a straightforward method to genetically program material viscoelasticity and biodegradability. Finally, these materials protect and sustain viability of encapsulated human fibroblasts, hepatocytes, embryonic kidney (HEK), and embryonic stem-cell-derived cardiomyocytes (hESC-CMs) through culture, injection, and transcutaneous implantation in mice. These injectable XTEN-based hydrogels show promise for both in vitro cell culture and in vivo cell transplantation applications.
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Affiliation(s)
| | - Mary O'Kelly Boit
- Department of Chemical EngineeringUniversity of WashingtonSeattleWA98105USA
| | | | - Fan Zhang
- Department of BioengineeringUniversity of WashingtonSeattleWA98105USA
| | - Ryan D. Kibler
- Department of BiochemistryUniversity of WashingtonSeattleWA98105USA
- Institute for Protein DesignUniversity of WashingtonSeattleWA98105USA
| | - Jack W. Hoye
- Department of Chemical EngineeringUniversity of WashingtonSeattleWA98105USA
| | - Olivia Prado
- Department of BioengineeringUniversity of WashingtonSeattleWA98105USA
| | - Peter B. Rapp
- Flagship Labs 83, Inc.135 Morrissey Blvd.BostonMA02125USA
| | - Charles E. Murry
- Department of BioengineeringUniversity of WashingtonSeattleWA98105USA
- Institute of Stem Cell & Regenerative MedicineUniversity of WashingtonSeattleWA98109USA
- Department of Laboratory Medicine & PathologyUniversity of WashingtonSeattleWA98195USA
- Department of Medicine/CardiologyUniversity of WashingtonSeattleWA98109USA
| | - Kelly R. Stevens
- Department of BioengineeringUniversity of WashingtonSeattleWA98105USA
- Institute of Stem Cell & Regenerative MedicineUniversity of WashingtonSeattleWA98109USA
- Department of Laboratory Medicine & PathologyUniversity of WashingtonSeattleWA98195USA
| | - Cole A. DeForest
- Department of Chemical EngineeringUniversity of WashingtonSeattleWA98105USA
- Department of BioengineeringUniversity of WashingtonSeattleWA98105USA
- Institute for Protein DesignUniversity of WashingtonSeattleWA98105USA
- Institute of Stem Cell & Regenerative MedicineUniversity of WashingtonSeattleWA98109USA
- Department of ChemistryUniversity of WashingtonSeattleWA98105USA
- Molecular Engineering & Sciences InstituteUniversity of WashingtonSeattleWA98105USA
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Singh CSB, Johns KM, Kari S, Munro L, Mathews A, Fenninger F, Pfeifer CG, Jefferies WA. Conclusive demonstration of iatrogenic Alzheimer's disease transmission in a model of stem cell transplantation. Stem Cell Reports 2024; 19:456-468. [PMID: 38552634 PMCID: PMC11096610 DOI: 10.1016/j.stemcr.2024.02.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 02/27/2024] [Accepted: 02/28/2024] [Indexed: 04/12/2024] Open
Abstract
The risk of iatrogenic disease is often underestimated as a concern in contemporary medical procedures, encompassing tissue and organ transplantation, stem cell therapies, blood transfusions, and the administration of blood-derived products. In this context, despite the prevailing belief that Alzheimer's disease (AD) manifests primarily in familial and sporadic forms, our investigation reveals an unexpected transplantable variant of AD in a preclinical context, potentially indicating iatrogenic transmission in AD patients. Through adoptive transplantation of donor bone marrow stem cells carrying a mutant human amyloid precursor protein (APP) transgene into either APP-deficient knockout or normal recipient animals, we observed rapid development of AD pathological hallmarks. These pathological features were significantly accelerated and emerged within 6-9 months post transplantation and included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated β-amyloid levels, and cognitive impairment. Furthermore, our findings underscore the contribution of β-amyloid burden originating outside of the central nervous system to AD pathogenesis within the brain. We conclude that stem cell transplantation from donors harboring a pathogenic mutant allele can effectively transfer central nervous system diseases to healthy recipients, mirroring the pathogenesis observed in the donor. Consequently, our observations advocate for genomic sequencing of donor specimens prior to tissue, organ, or stem cell transplantation therapies, as well as blood transfusions and blood-derived product administration, to mitigate the risk of iatrogenic diseases.
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Affiliation(s)
- Chaahat S B Singh
- Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada
| | - Kelly Marie Johns
- Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada
| | - Suresh Kari
- Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada
| | - Lonna Munro
- Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada
| | - Angela Mathews
- Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada
| | - Franz Fenninger
- Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada; Department of Microbiology and Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada
| | - Cheryl G Pfeifer
- Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada
| | - Wilfred A Jefferies
- Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; Department of Microbiology and Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; Department of Zoology, University of British Columbia, 6270 University Boulevard, Vancouver, BC V6T 1Z4, Canada; Department of Urologic Sciences, University of British Columbia, Level 6, 2775 Laurel Street, Vancouver, BC V5Z 1M9 Canada.
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Wu Y, Meng X, Cheng WY, Yan Z, Li K, Wang J, Jiang T, Zhou F, Wong KH, Zhong C, Dong Y, Gao S. Can pluripotent/multipotent stem cells reverse Parkinson's disease progression? Front Neurosci 2024; 18:1210447. [PMID: 38356648 PMCID: PMC10864507 DOI: 10.3389/fnins.2024.1210447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 01/02/2024] [Indexed: 02/16/2024] Open
Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by continuous and selective degeneration or death of dopamine neurons in the midbrain, leading to dysfunction of the nigrostriatal neural circuits. Current clinical treatments for PD include drug treatment and surgery, which provide short-term relief of symptoms but are associated with many side effects and cannot reverse the progression of PD. Pluripotent/multipotent stem cells possess a self-renewal capacity and the potential to differentiate into dopaminergic neurons. Transplantation of pluripotent/multipotent stem cells or dopaminergic neurons derived from these cells is a promising strategy for the complete repair of damaged neural circuits in PD. This article reviews and summarizes the current preclinical/clinical treatments for PD, their efficacies, and the advantages/disadvantages of various stem cells, including pluripotent and multipotent stem cells, to provide a detailed overview of how these cells can be applied in the treatment of PD, as well as the challenges and bottlenecks that need to be overcome in future translational studies.
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Affiliation(s)
- Yongkang Wu
- Key Laboratory of Adolescent Health Evaluation and Sports Intervention, Ministry of Education, East China Normal University, Shanghai, China
| | - Xiangtian Meng
- Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Wai-Yin Cheng
- Research Institute for Future Food, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China
- Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China
| | - Zhichao Yan
- Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Keqin Li
- Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jian Wang
- Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Tianfang Jiang
- Department of Neurology, Shanghai Eighth People’s Hospital Affiliated to Jiangsu University, Shanghai, China
| | - Fei Zhou
- Department of Neurology, Third Affiliated Hospital of Navy Military Medical University, Shanghai, China
| | - Ka-Hing Wong
- Research Institute for Future Food, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China
- Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China
| | - Chunlong Zhong
- Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yi Dong
- Key Laboratory of Adolescent Health Evaluation and Sports Intervention, Ministry of Education, East China Normal University, Shanghai, China
| | - Shane Gao
- Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
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Lee MH, Um KH, Lee SW, Sun YJ, Gu DH, Jo YO, Kim SH, Seol W, Hwang H, Baek K, Choi JW. Bi-directional regulation of AIMP2 and its splice variant on PARP-1-dependent neuronal cell death; Therapeutic implication for Parkinson's disease. Acta Neuropathol Commun 2024; 12:5. [PMID: 38172953 PMCID: PMC10765824 DOI: 10.1186/s40478-023-01697-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 11/28/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND Parthanatos represents a critical molecular aspect of Parkinson's disease, wherein AIMP2 aberrantly activates PARP-1 through direct physical interaction. Although AIMP2 ought to be a therapeutic target for the disease, regrettably, it is deemed undruggable due to its non-enzymatic nature and predominant localization within the tRNA synthetase multi-complex. Instead, AIMP2 possesses an antagonistic splice variant, designated DX2, which counteracts AIMP2-induced apoptosis in the p53 or inflammatory pathway. Consequently, we examined whether DX2 competes with AIMP2 for PARP-1 activation and is therapeutically effective in Parkinson's disease. METHODS The binding affinity of AIMP2 and DX2 to PARP-1 was contrasted through immunoprecipitation. The efficacy of DX2 in neuronal cell death was assessed under 6-OHDA and H2O2 in vitro conditions. Additionally, endosomal and exosomal activity of synaptic vesicles was gauged in AIMP2 or DX2 overexpressed hippocampal primary neurons utilizing optical live imaging with VAMP-vGlut1 probes. To ascertain the role of DX2 in vivo, rotenone-induced behavioral alterations were compared between wild-type and DX2 transgenic animals. A DX2-encoding self-complementary adeno-associated virus (scAAV) was intracranially injected into 6-OHDA induced in vivo animal models, and their mobility was examined. Subsequently, the isolated brain tissues were analyzed. RESULTS DX2 translocates into the nucleus upon ROS stress more rapidly than AIMP2. The binding affinity of DX2 to PARP-1 appeared to be more robust compared to that of AIMP2, resulting in the inhibition of PARP-1 induced neuronal cell death. DX2 transgenic animals exhibited neuroprotective behavior in rotenone-induced neuronal damage conditions. Following a single intracranial injection of AAV-DX2, both behavior and mobility were consistently ameliorated in neurodegenerative animal models induced by 6-OHDA. CONCLUSION AIMP2 and DX2 are proposed to engage in bidirectional regulation of parthanatos. They physically interact with PARP-1. Notably, DX2's cell survival properties manifest exclusively in the context of abnormal AIMP2 accumulation, devoid of any tumorigenic effects. This suggests that DX2 could represent a distinctive therapeutic target for addressing Parkinson's disease in patients.
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Affiliation(s)
- Min Hak Lee
- Department of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea
- Department of Biomedical and Pharmaceutical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
- Department of Regulatory Science, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Ki-Hwan Um
- Department of Biomedical and Pharmaceutical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
- Department of Regulatory Science, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Seok Won Lee
- Department of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea
- Department of Biomedical and Pharmaceutical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Ye Ji Sun
- Department of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea
- Department of Biomedical and Pharmaceutical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
- Department of Regulatory Science, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Da-Hye Gu
- Department of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea
- Department of Biomedical and Pharmaceutical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Young Ok Jo
- Department of Neuroscience, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Sung Hyun Kim
- Department of Neuroscience, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
- Department of Physiology, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Wongi Seol
- InAm Neuroscience Research Center, Sanbon Medical Center, College of Medicine, Wonkwang University, Sanbonro 321, Gunposi, Gyeonggido, 15865, Republic of Korea
| | - Hyorin Hwang
- Generoath Ltd., Seoul, 04168, Republic of Korea
- Department of Pharmacology, College of Dentistry and Research Institute of Oral Science, Gangneung-Wonju National University, Gangneung, Gangwon-Do, 25457, Republic of Korea
| | - Kyunghwa Baek
- Department of Pharmacology, College of Dentistry and Research Institute of Oral Science, Gangneung-Wonju National University, Gangneung, Gangwon-Do, 25457, Republic of Korea
| | - Jin Woo Choi
- Department of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea.
- Department of Biomedical and Pharmaceutical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
- Department of Regulatory Science, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea.
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Hashida R, Kawabata T. Structural Perspective of NR4A Nuclear Receptor Family and Their Potential Endogenous Ligands. Biol Pharm Bull 2024; 47:580-590. [PMID: 38432913 DOI: 10.1248/bpb.b23-00600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2024]
Abstract
There are 48 nuclear receptors in the human genome, and many members of this superfamily have been implicated in human diseases. The NR4A nuclear receptor family consisting of three members, NR4A1, NR4A2, and NR4A3 (formerly annotated as Nur77, Nurr1, and NOR1, respectively), are still orphan receptors but exert pathological effects on immune-related and neurological diseases. We previously reported that prostaglandin A1 (PGA1) and prostaglandin A2 (PGA2) are potent activators of NR4A3, which bind directly to the ligand-binding domain (LBD) of the receptor. Recently, the co-crystallographic structures of NR4A2-LBD bound to PGA1 and PGA2 were reported, followed by reports of the neuroprotective effects of these possible endogenous ligands in mouse models of Parkinson's disease. Based on these structures, we modeled the binding structures of the other two members (NR4A1 and NR4A3) with these potential endogenous ligands using a template-based modeling method, and reviewed the similarity and diversity of ligand-binding mechanisms in the nuclear receptor family.
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Affiliation(s)
- Ryoichi Hashida
- Genox Research Inc
- Department of Microbiology, Matsumoto Dental University
| | - Takeshi Kawabata
- Department of Applied Information Sciences, Graduate School of Information Sciences, Tohoku University
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11
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Nasrolahi A, Shabani Z, Sadigh-Eteghad S, Salehi-Pourmehr H, Mahmoudi J. Stem Cell Therapy for the Treatment of Parkinson's Disease: What Promise Does it Hold? Curr Stem Cell Res Ther 2024; 19:185-199. [PMID: 36815638 DOI: 10.2174/1574888x18666230222144116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 01/04/2023] [Accepted: 01/06/2023] [Indexed: 02/24/2023]
Abstract
Parkinson's disease (PD) is a common, progressive neurodegenerative disorder characterized by substantia nigra dopamine cell death and a varied clinical picture that affects older people. Although more than two centuries have passed since the earliest attempts to find a cure for PD, it remains an unresolved problem. With this in mind, cell replacement therapy is a new strategy for treating PD. This novel approach aims to replace degenerated dopaminergic (DAergic) neurons with new ones or provide a new source of cells that can differentiate into DAergic neurons. Induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), neural stem cells (NSCs), and embryonic stem cells (ESCs) are among the cells considered for transplantation therapies. Recently disease-modifying strategies like cell replacement therapies combined with other therapeutic approaches, such as utilizing natural compounds or biomaterials, are proposed to modify the underlying neurodegeneration. In the present review, we discuss the current advances in cell replacement therapy for PD and summarize the existing experimental and clinical evidence supporting this approach.
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Affiliation(s)
- Ava Nasrolahi
- Infectious Ophthalmologic Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Cellular and Molecular Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Zahra Shabani
- Center for Cerebrovascular Research, University of California, San Francisco, California, USA
| | - Saeed Sadigh-Eteghad
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hanieh Salehi-Pourmehr
- Research Center for Evidence-Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Javad Mahmoudi
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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12
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Barker RA, Buttery PC. Disease-specific interventions: The use of cell and gene therapies for Parkinson disease. HANDBOOK OF CLINICAL NEUROLOGY 2024; 205:171-191. [PMID: 39341654 DOI: 10.1016/b978-0-323-90120-8.00003-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/01/2024]
Abstract
Approaches to repair the brain around the loss of the nigrostriatal dopaminergic pathways in Parkinson disease (PD) are not new and have been attempted over many years. However, of late, the situation has moved forward in two main ways. In the case of cell therapies, the ability to make large numbers of authentic midbrain dopaminergic neuroblasts from human pluripotent stem cell sources has turned what was an interesting avenue of research into a major area of investment and trialing, by academics in conjunction with Pharma. In the case of gene therapies, their use around dopamine replacement has waned, as the interest in using them for disease modification targeting PD-specific pathways has grown. In this chapter, we discuss all these developments and the current status of cell and gene therapies for PD.
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Affiliation(s)
- Roger A Barker
- Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
| | - Philip C Buttery
- Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
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13
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Kasturi M, Mathur V, Gadre M, Srinivasan V, Vasanthan KS. Three Dimensional Bioprinting for Hepatic Tissue Engineering: From In Vitro Models to Clinical Applications. Tissue Eng Regen Med 2024; 21:21-52. [PMID: 37882981 PMCID: PMC10764711 DOI: 10.1007/s13770-023-00576-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 07/07/2023] [Accepted: 07/11/2023] [Indexed: 10/27/2023] Open
Abstract
Fabrication of functional organs is the holy grail of tissue engineering and the possibilities of repairing a partial or complete liver to treat chronic liver disorders are discussed in this review. Liver is the largest gland in the human body and plays a responsible role in majority of metabolic function and processes. Chronic liver disease is one of the leading causes of death globally and the current treatment strategy of organ transplantation holds its own demerits. Hence there is a need to develop an in vitro liver model that mimics the native microenvironment. The developed model should be a reliable to understand the pathogenesis, screen drugs and assist to repair and replace the damaged liver. The three-dimensional bioprinting is a promising technology that recreates in vivo alike in vitro model for transplantation, which is the goal of tissue engineers. The technology has great potential due to its precise control and its ability to homogeneously distribute cells on all layers in a complex structure. This review gives an overview of liver tissue engineering with a special focus on 3D bioprinting and bioinks for liver disease modelling and drug screening.
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Affiliation(s)
- Meghana Kasturi
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Vidhi Mathur
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Mrunmayi Gadre
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Varadharajan Srinivasan
- Department of Civil Engineering, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Kirthanashri S Vasanthan
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
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14
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López-Ornelas A, Escobedo-Avila I, Ramírez-García G, Lara-Rodarte R, Meléndez-Ramírez C, Urrieta-Chávez B, Barrios-García T, Cáceres-Chávez VA, Flores-Ponce X, Carmona F, Reynoso CA, Aguilar C, Kerik NE, Rocha L, Verdugo-Díaz L, Treviño V, Bargas J, Ramos-Mejía V, Fernández-Ruiz J, Campos-Romo A, Velasco I. Human Embryonic Stem Cell-Derived Immature Midbrain Dopaminergic Neurons Transplanted in Parkinsonian Monkeys. Cells 2023; 12:2738. [PMID: 38067166 PMCID: PMC10706241 DOI: 10.3390/cells12232738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 11/20/2023] [Accepted: 11/23/2023] [Indexed: 12/18/2023] Open
Abstract
Human embryonic stem cells (hESCs) differentiate into specialized cells, including midbrain dopaminergic neurons (DANs), and Non-human primates (NHPs) injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine develop some alterations observed in Parkinson's disease (PD) patients. Here, we obtained well-characterized DANs from hESCs and transplanted them into two parkinsonian monkeys to assess their behavioral and imaging changes. DANs from hESCs expressed dopaminergic markers, generated action potentials, and released dopamine (DA) in vitro. These neurons were transplanted bilaterally into the putamen of parkinsonian NHPs, and using magnetic resonance imaging techniques, we calculated the fractional anisotropy (FA) and mean diffusivity (MD), both employed for the first time for these purposes, to detect in vivo axonal and cellular density changes in the brain. Likewise, positron-emission tomography scans were performed to evaluate grafted DANs. Histological analyses identified grafted DANs, which were quantified stereologically. After grafting, animals showed signs of partially improved motor behavior in some of the HALLWAY motor tasks. Improvement in motor evaluations was inversely correlated with increases in bilateral FA. MD did not correlate with behavior but presented a negative correlation with FA. We also found higher 11C-DTBZ binding in positron-emission tomography scans associated with grafts. Higher DA levels measured by microdialysis after stimulation with a high-potassium solution or amphetamine were present in grafted animals after ten months, which has not been previously reported. Postmortem analysis of NHP brains showed that transplanted DANs survived in the putamen long-term, without developing tumors, in immunosuppressed animals. Although these results need to be confirmed with larger groups of NHPs, our molecular, behavioral, biochemical, and imaging findings support the integration and survival of human DANs in this pre-clinical PD model.
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Affiliation(s)
- Adolfo López-Ornelas
- Instituto de Fisiología Celular—Neurociencias, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (A.L.-O.); (I.E.-A.); (R.L.-R.); (C.M.-R.); (B.U.-C.); (V.A.C.-C.); (X.F.-P.); (J.B.)
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico
- División de Investigación, Hospital Juárez de México, Mexico City 07760, Mexico
| | - Itzel Escobedo-Avila
- Instituto de Fisiología Celular—Neurociencias, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (A.L.-O.); (I.E.-A.); (R.L.-R.); (C.M.-R.); (B.U.-C.); (V.A.C.-C.); (X.F.-P.); (J.B.)
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico
- Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (L.V.-D.); (J.F.-R.)
- Unidad Periférica de Neurociencias, Facultad de Medicina, Universidad Nacional Autónoma de México, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico;
| | - Gabriel Ramírez-García
- Unidad Periférica de Neurociencias, Facultad de Medicina, Universidad Nacional Autónoma de México, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico;
| | - Rolando Lara-Rodarte
- Instituto de Fisiología Celular—Neurociencias, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (A.L.-O.); (I.E.-A.); (R.L.-R.); (C.M.-R.); (B.U.-C.); (V.A.C.-C.); (X.F.-P.); (J.B.)
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico
| | - César Meléndez-Ramírez
- Instituto de Fisiología Celular—Neurociencias, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (A.L.-O.); (I.E.-A.); (R.L.-R.); (C.M.-R.); (B.U.-C.); (V.A.C.-C.); (X.F.-P.); (J.B.)
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico
| | - Beetsi Urrieta-Chávez
- Instituto de Fisiología Celular—Neurociencias, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (A.L.-O.); (I.E.-A.); (R.L.-R.); (C.M.-R.); (B.U.-C.); (V.A.C.-C.); (X.F.-P.); (J.B.)
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico
| | - Tonatiuh Barrios-García
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey 64710, Mexico; (T.B.-G.); (V.T.)
| | - Verónica A. Cáceres-Chávez
- Instituto de Fisiología Celular—Neurociencias, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (A.L.-O.); (I.E.-A.); (R.L.-R.); (C.M.-R.); (B.U.-C.); (V.A.C.-C.); (X.F.-P.); (J.B.)
| | - Xóchitl Flores-Ponce
- Instituto de Fisiología Celular—Neurociencias, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (A.L.-O.); (I.E.-A.); (R.L.-R.); (C.M.-R.); (B.U.-C.); (V.A.C.-C.); (X.F.-P.); (J.B.)
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico
| | - Francia Carmona
- Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav), Mexico City 07360, Mexico; (F.C.); (L.R.)
| | - Carlos Alberto Reynoso
- Molecular Imaging PET-CT Unit, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico; (C.A.R.); (C.A.); (N.E.K.)
| | - Carlos Aguilar
- Molecular Imaging PET-CT Unit, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico; (C.A.R.); (C.A.); (N.E.K.)
| | - Nora E. Kerik
- Molecular Imaging PET-CT Unit, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico; (C.A.R.); (C.A.); (N.E.K.)
| | - Luisa Rocha
- Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav), Mexico City 07360, Mexico; (F.C.); (L.R.)
| | - Leticia Verdugo-Díaz
- Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (L.V.-D.); (J.F.-R.)
| | - Víctor Treviño
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey 64710, Mexico; (T.B.-G.); (V.T.)
| | - José Bargas
- Instituto de Fisiología Celular—Neurociencias, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (A.L.-O.); (I.E.-A.); (R.L.-R.); (C.M.-R.); (B.U.-C.); (V.A.C.-C.); (X.F.-P.); (J.B.)
| | - Verónica Ramos-Mejía
- Gene Regulation, Stem Cells, and Development Group, GENYO-Centre for Genomics and Oncological Research Pfizer, University of Granada, Andalusian Regional Government, PTS, 18016 Granada, Spain;
| | - Juan Fernández-Ruiz
- Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (L.V.-D.); (J.F.-R.)
| | - Aurelio Campos-Romo
- Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (L.V.-D.); (J.F.-R.)
- Unidad Periférica de Neurociencias, Facultad de Medicina, Universidad Nacional Autónoma de México, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico;
| | - Iván Velasco
- Instituto de Fisiología Celular—Neurociencias, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; (A.L.-O.); (I.E.-A.); (R.L.-R.); (C.M.-R.); (B.U.-C.); (V.A.C.-C.); (X.F.-P.); (J.B.)
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico
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15
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Liu Y, Cheng J, Lu F, Li S, Ma Z, Du Y, Yuan Z, Lu C. 3,5-Dihydroxybenzoic Acid-Based Selective Dopamine Detection via Subsititution-Enhanced Kinetics Differences. Anal Chem 2023; 95:14944-14953. [PMID: 37772797 DOI: 10.1021/acs.analchem.3c02313] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/30/2023]
Abstract
The selective recognition of dopamine (DA) over other neurotransmitter analogues is difficult due to the similar molecular structure and chemical reactivity. In this study, substitution-regulated chemical reactivity of the sensing substrate is utilized to explore a novel DA detection probe with satisfying selectivity. As a case study, 3,5-dihydroxybenzoic acid (DHBA, carboxy-substituted resorcinol)-based probes have been explored for selective and ratiometric DA sensing. The carboxy substitution benefits the stabilization of the carbanion intermediate and the azamonardine product, which enhances the reaction kinetics and thermodynamics and subsequently facilitates selective DA recognition over other analogues and interferents. By exploring DHBA emission as the internal reference, ratiometric fluorescence variation is realized, which contributes to sensitive DA analysis. With the combination of logic gate and fluorometric analysis, DA detection in both low and high concentrations can be readily achieved. In addition, the DA analysis in biological samples and the enzymatic transformation of DA analogues in cerebrospinal fluid samples are achieved by the proposed DHBA probe.
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Affiliation(s)
- Yang Liu
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029, China
| | - Junqi Cheng
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029, China
| | - Fengniu Lu
- Department of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China
| | - Shuo Li
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029, China
| | - Zhiyong Ma
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029, China
| | - Yi Du
- Analysis Center, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China
| | - Zhiqin Yuan
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029, China
| | - Chao Lu
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029, China
- Green Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou 450001, China
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16
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Zhang Z, You Y, Ge M, Lin H, Shi J. Functional nanoparticle-enabled non-genetic neuromodulation. J Nanobiotechnology 2023; 21:319. [PMID: 37674191 PMCID: PMC10483742 DOI: 10.1186/s12951-023-02084-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 08/28/2023] [Indexed: 09/08/2023] Open
Abstract
Stimulating ion channels targeting in neuromodulation by external signals with the help of functionalized nanoparticles, which integrates the pioneering achievements in the fields of neurosciences and nanomaterials, has involved into a novel interdisciplinary field. The emerging technique developed in this field enable simple, remote, non-invasive, and spatiotemporally precise nerve regulations and disease therapeutics, beyond traditional treatment methods. In this paper, we define this emerging field as nano-neuromodulation and summarize the most recent developments of non-genetic nano-neuromodulation (non-genetic NNM) over the past decade based on the innovative design concepts of neuromodulation nanoparticle systems. These nanosystems, which feature diverse compositions, structures and synthesis approaches, could absorb certain exogenous stimuli like light, sound, electric or magnetic signals, and subsequently mediate mutual transformations between above signals, or chemical reactions, to regulate stimuli-sensitive ion channels and ion migrations which play vital roles in the nervous system. We will also discuss the obstacles and challenges in the future development of non-genetic NNM, and propose its future developments, to add the further progress of this promising field.
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Affiliation(s)
- Zhimin Zhang
- Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai, 200050, People's Republic of China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China
| | - Yanling You
- Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai, 200050, People's Republic of China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China
| | - Min Ge
- Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai, 200050, People's Republic of China.
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
| | - Han Lin
- Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai, 200050, People's Republic of China.
- Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, 200331, People's Republic of China.
| | - Jianlin Shi
- Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai, 200050, People's Republic of China
- Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, 200331, People's Republic of China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China
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17
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Zhang Z, You Y, Ge M, Lin H, Shi J. Functional nanoparticle-enabled non-genetic neuromodulation. J Nanobiotechnology 2023; 21:319. [DOI: doi.org/10.1186/s12951-023-02084-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 08/28/2023] [Indexed: 09/08/2023] Open
Abstract
AbstractStimulating ion channels targeting in neuromodulation by external signals with the help of functionalized nanoparticles, which integrates the pioneering achievements in the fields of neurosciences and nanomaterials, has involved into a novel interdisciplinary field. The emerging technique developed in this field enable simple, remote, non-invasive, and spatiotemporally precise nerve regulations and disease therapeutics, beyond traditional treatment methods. In this paper, we define this emerging field as nano-neuromodulation and summarize the most recent developments of non-genetic nano-neuromodulation (non-genetic NNM) over the past decade based on the innovative design concepts of neuromodulation nanoparticle systems. These nanosystems, which feature diverse compositions, structures and synthesis approaches, could absorb certain exogenous stimuli like light, sound, electric or magnetic signals, and subsequently mediate mutual transformations between above signals, or chemical reactions, to regulate stimuli-sensitive ion channels and ion migrations which play vital roles in the nervous system. We will also discuss the obstacles and challenges in the future development of non-genetic NNM, and propose its future developments, to add the further progress of this promising field.
Graphical Abstract
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18
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Hey G, Willman M, Patel A, Goutnik M, Willman J, Lucke-Wold B. Stem Cell Scaffolds for the Treatment of Spinal Cord Injury—A Review. BIOMECHANICS 2023; 3:322-342. [PMID: 37664542 PMCID: PMC10469078 DOI: 10.3390/biomechanics3030028] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/05/2023]
Abstract
Spinal cord injury (SCI) is a profoundly debilitating yet common central nervous system condition resulting in significant morbidity and mortality rates. Major causes of SCI encompass traumatic incidences such as motor vehicle accidents, falls, and sports injuries. Present treatment strategies for SCI aim to improve and enhance neurologic functionality. The ability for neural stem cells (NSCs) to differentiate into diverse neural and glial cell precursors has stimulated the investigation of stem cell scaffolds as potential therapeutics for SCI. Various scaffolding modalities including composite materials, natural polymers, synthetic polymers, and hydrogels have been explored. However, most trials remain largely in the preclinical stage, emphasizing the need to further develop and refine these treatment strategies before clinical implementation. In this review, we delve into the physiological processes that underpin NSC differentiation, including substrates and signaling pathways required for axonal regrowth post-injury, and provide an overview of current and emerging stem cell scaffolding platforms for SCI.
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Affiliation(s)
- Grace Hey
- College of Medicine, University of Florida, Gainesville, FL 32611, USA
| | - Matthew Willman
- College of Medicine, University of Florida, Gainesville, FL 32611, USA
| | - Aashay Patel
- College of Medicine, University of Florida, Gainesville, FL 32611, USA
| | - Michael Goutnik
- College of Medicine, University of Florida, Gainesville, FL 32611, USA
| | - Jonathan Willman
- College of Medicine, University of Florida, Gainesville, FL 32611, USA
| | - Brandon Lucke-Wold
- Department of Neurosurgery, University of Florida, Gainesville, FL 32611, USA
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19
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Zhao W, Tu H, Chen J, Wang J, Liu H, Zhang F, Li J. Functionalized hydrogels in neural injury repairing. Front Neurosci 2023; 17:1199299. [PMID: 37404462 PMCID: PMC10315583 DOI: 10.3389/fnins.2023.1199299] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 04/27/2023] [Indexed: 07/06/2023] Open
Abstract
Repairing injuries to the nervous system has always been a prominent topic in clinical research. Direct suturing and nerve displacement surgery are the primary treatment options, but they may not be suitable for long nerve injuries and may require sacrificing the functionality of other autologous nerves. With the emergence of tissue engineering, hydrogel materials have been identified as a promising technology with clinical translation potential for repairing nervous system injuries due to their excellent biocompatibility and ability to release or deliver functional ions. By controlling their composition and structure, hydrogels can be Functionalized and almost fully matched with nerve tissue and even simulate nerve conduction function and mechanical properties. Thus, they are suitable for repairing injuries to both the central and peripheral nervous systems. This article provides a review of recent research progress in functionalized hydrogels for nerve injury repair, highlighting the design differences among various materials and future research directions. We strongly believe that the development of functionalized hydrogels has great potential for improving the clinical treatment of nerve injuries.
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Affiliation(s)
- Wenqian Zhao
- College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, China
| | - Hui Tu
- College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, China
| | - Jianxiao Chen
- Department of Nephrology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
| | - Jing Wang
- College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, China
| | - Haoting Liu
- College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, China
| | - Fengshou Zhang
- College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, China
| | - Jing Li
- Office of Science and Technology, Henan University of Science and Technology, Luoyang, China
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20
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Wang X, Dai X, Chen Y. Sonopiezoelectric Nanomedicine and Materdicine. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2023:e2301693. [PMID: 37093550 DOI: 10.1002/smll.202301693] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 04/02/2023] [Indexed: 05/03/2023]
Abstract
Endogenous electric field is ubiquitous in a multitude of important living activities such as bone repair, cell signal transduction, and nerve regeneration, signifying that regulating the electric field in organisms is highly beneficial to maintain organism health. As an emerging and promising research direction, piezoelectric nanomedicine and materdicine precisely activated by ultrasound with synergetic advantages of deep tissue penetration, remote spatiotemporal selectivity, and mechanical-electrical energy interconversion, have been progressively utilized for disease treatment and tissue repair by participating in the modulation of endogenous electric field. This specific nanomedicine utilizing piezoelectric effect activated by ultrasound is typically regarded as "sonopiezoelectric nanomedicine". This comprehensive review summarizes and discusses the substantially employed sonopiezoelectric nanomaterials and nanotherapies to provide an insight into the internal mechanism of the corresponding biological behavior/effect of sonopiezoelectric biomaterials in versatile disease treatments. This review primarily focuses on the sonopiezoelectric biomaterials for biosensing, drug delivery, tumor therapy, tissue regeneration, antimicrobia, and further illuminates the underlying sonopiezoelectric mechanism. In addition, the challenges and developments/prospects of sonopiezoelectric nanomedicine are analyzed for promoting the further clinical translation. It is earnestly expected that this kind of nanomedicine/biomaterials-enabled sonopiezoelectric technology will provoke the comprehensive investigation and promote the clinical development of the next-generation multifunctional materdicine.
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Affiliation(s)
- Xue Wang
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China
| | - Xinyue Dai
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China
| | - Yu Chen
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China
- School of Medicine, Shanghai University, Shanghai, 200444, P. R. China
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21
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Qiao R, Fu C, Forgham H, Javed I, Huang X, Zhu J, Whittaker AK, Davis TP. Magnetic Iron Oxide Nanoparticles for Brain Imaging and Drug Delivery. Adv Drug Deliv Rev 2023; 197:114822. [PMID: 37086918 DOI: 10.1016/j.addr.2023.114822] [Citation(s) in RCA: 70] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 03/14/2023] [Accepted: 04/09/2023] [Indexed: 04/24/2023]
Abstract
Central nervous system (CNS) disorders affect as many as 1.5 billion people globally. The limited delivery of most imaging and therapeutic agents into the brain is a major challenge for treatment of CNS disorders. With the advent of nanotechnologies, controlled delivery of drugs with nanoparticles holds great promise in CNS disorders for overcoming the blood-brain barrier (BBB) and improving delivery efficacy. In recent years, magnetic iron oxide nanoparticles (MIONPs) have stood out as a promising theranostic nanoplatform for brain imaging and drug delivery as they possess unique physical properties and biodegradable characteristics. In this review, we summarize the recent advances in MIONP-based platforms as imaging and drug delivery agents for brain diseases. We firstly introduce the methods of synthesis and surface functionalization of MIONPs with emphasis on the inclusion of biocompatible polymers that allow for the addition of tailored physicochemical properties. We then discuss the recent advances in in vivo imaging and drug delivery applications using MIONPs. Finally, we present a perspective on the remaining challenges and possible future directions for MIONP-based brain delivery systems.
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Affiliation(s)
- Ruirui Qiao
- Australian Institute of Bioengineering & Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia
| | - Changkui Fu
- Australian Institute of Bioengineering & Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia
| | - Helen Forgham
- Australian Institute of Bioengineering & Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia
| | - Ibrahim Javed
- Australian Institute of Bioengineering & Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia
| | - Xumin Huang
- Australian Institute of Bioengineering & Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia
| | - Jiayuan Zhu
- Australian Institute of Bioengineering & Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia
| | - Andrew K Whittaker
- Australian Institute of Bioengineering & Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia.
| | - Thomas P Davis
- Australian Institute of Bioengineering & Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia.
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22
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Suhariningsih S, Astuti SD, Kusumawati HN, Mahmud AF, Septriana M, Rozykulyyeva L, Susilo Y, Syahrom A. Effect of 650 nm laser photobiomodulation therapy on the HT-7 ( shenmen) acupoint in the Mus musculus model of Parkinson's disease. Heliyon 2023; 9:e15295. [PMID: 37123890 PMCID: PMC10130853 DOI: 10.1016/j.heliyon.2023.e15295] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 03/22/2023] [Accepted: 03/31/2023] [Indexed: 05/02/2023] Open
Abstract
Background Parkinson's disease is one of the neurodegenerative conditions that impacts 1-2% of the world's population. The only effective therapy for this condition today is to restore the biochemical function of the diseased dopamine neurons by giving them Levodopa or L-3,4-dihydroxyphenylalanine (l-DOPA). The risk of progenitor stem cells, though, is the growth of teratomas or the uncontrolled growth of cells. As a result, an alternative or additional method is needed, such as photobiomodulation therapy using a laser diode. In this research, male mice (Mus musculus), which were used as models for Parkinson's disease in an in vivo paraquat study, to determine the optimal dose of photobiomodulation therapy and a laser diode was used as a treatment. Methods The three sample groups are Group P-L- (control group, induced by 0.9% NaCl), Group P + L- (only caused by paraquat), and Group P + L+. (Treatment group, treated by paraquat and photobiomodulation therapy with a laser diode). Photobiomodulation treatment doses of 0.14 J, 0.29 J, 0.37 J, 0.76 J, 1.14 J, and 1.52 J were used in the P+L+ subgroups (6 groups). The laser diode generated a continuous wave with a wavelength of 658 nm, a beam spot of 2.10 mm, and an output power of 15.42 mW. After treatment, the histopathology results of each sample were inspected under a microscope. Result In Parkinson's disease-affected mice, paraquat has been shown to reduce the number of neurons. According to the results of the histopathological examination, photobiomodulation therapy using a laser diode (P + L+) on the HT-7 (Shenmen) may raise the quantity of neurons and the proportion of healthy cells in the mouse brain. Conclusion The effective radiated energy of the photobiomodulation therapy using laser diode treatment on the muscle musculus cell model of Parkinson's disease is 0.76 J.
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Affiliation(s)
- Suhariningsih Suhariningsih
- Department of Physics, Faculty of Sciences and Technology, Airlangga University, Surabaya, 60115, Indonesia
- Biophysics and Medical Physics Research Group, Faculty of Sciences and Technology, Airlangga University, Surabaya, 60115, Indonesia
- Traditional Medicine Study Program, Faculty of Vocational Study, Airlangga University, Surabaya, 60286, Indonesia
| | - Suryani Dyah Astuti
- Department of Physics, Faculty of Sciences and Technology, Airlangga University, Surabaya, 60115, Indonesia
- Biophysics and Medical Physics Research Group, Faculty of Sciences and Technology, Airlangga University, Surabaya, 60115, Indonesia
- Biomedical Engineering Post Graduate Program, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia
- Corresponding author. Airlangga University Faculty of Science and Technology, Universitas Airlangga Fakultas Sains dan Teknologi, Surabaya, East Java, 60115, Indonesia
| | - Herdiani Nur Kusumawati
- Biomedical Engineering Post Graduate Program, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia
| | - Amalia Fitriana Mahmud
- Department of Physics, Faculty of Sciences and Technology, Airlangga University, Surabaya, 60115, Indonesia
| | - Maya Septriana
- Traditional Medicine Study Program, Faculty of Vocational Study, Airlangga University, Surabaya, 60286, Indonesia
| | - Lale Rozykulyyeva
- Biomedical Engineering Post Graduate Program, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia
| | - Yunus Susilo
- Faculty of Engineering, Dr Soetomo University, Surabaya, 60118, Indonesia
| | - Ardiansyah Syahrom
- Department of Applied Mechanics and Design, Faculty of Mechanical Engineering, Universiti Teknologi Malaysia, 81310 Johor Bahru, Malaysia
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23
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Krishnan SK, Nataraj N, Meyyappan M, Pal U. Graphene-Based Field-Effect Transistors in Biosensing and Neural Interfacing Applications: Recent Advances and Prospects. Anal Chem 2023; 95:2590-2622. [PMID: 36693046 PMCID: PMC11386440 DOI: 10.1021/acs.analchem.2c03399] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- Siva Kumar Krishnan
- CONACYT-Instituto de Física, Benemérita Universidad Autónoma de Puebla, Apdo. Postal J-48, Puebla72570, Mexico
| | - Nandini Nataraj
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, No.1, Section 3, Chung-Hsiao East Road, Taipei106, Taiwan
| | - M Meyyappan
- Centre for Nanotechnology, Indian Institute of Technology, Guwahati781039, Assam, India
| | - Umapada Pal
- Instituto de Física, Benemérita Universidad Autónoma de Puebla, Apdo. Postal J-48, Puebla72570, Mexico
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24
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Peng Z, Fiorani A, Akai K, Murata M, Otake A, Einaga Y. Boron-Doped Diamond as a Quasi-Reference Electrode. Anal Chem 2022; 94:16831-16837. [DOI: 10.1021/acs.analchem.2c03923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Zhen Peng
- Department of Chemistry, Keio University, 3-14-1 Hiyoshi, Yokohama223-8522, Japan
| | - Andrea Fiorani
- Department of Chemistry, Keio University, 3-14-1 Hiyoshi, Yokohama223-8522, Japan
| | - Kazumi Akai
- Department of Chemistry, Keio University, 3-14-1 Hiyoshi, Yokohama223-8522, Japan
| | - Michio Murata
- Department of Chemistry, Keio University, 3-14-1 Hiyoshi, Yokohama223-8522, Japan
| | - Atsushi Otake
- Department of Chemistry, Keio University, 3-14-1 Hiyoshi, Yokohama223-8522, Japan
| | - Yasuaki Einaga
- Department of Chemistry, Keio University, 3-14-1 Hiyoshi, Yokohama223-8522, Japan
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25
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Cvekl A, Camerino MJ. Generation of Lens Progenitor Cells and Lentoid Bodies from Pluripotent Stem Cells: Novel Tools for Human Lens Development and Ocular Disease Etiology. Cells 2022; 11:3516. [PMID: 36359912 PMCID: PMC9658148 DOI: 10.3390/cells11213516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 10/31/2022] [Accepted: 11/02/2022] [Indexed: 11/09/2022] Open
Abstract
In vitro differentiation of human pluripotent stem cells (hPSCs) into specialized tissues and organs represents a powerful approach to gain insight into those cellular and molecular mechanisms regulating human development. Although normal embryonic eye development is a complex process, generation of ocular organoids and specific ocular tissues from pluripotent stem cells has provided invaluable insights into the formation of lineage-committed progenitor cell populations, signal transduction pathways, and self-organization principles. This review provides a comprehensive summary of recent advances in generation of adenohypophyseal, olfactory, and lens placodes, lens progenitor cells and three-dimensional (3D) primitive lenses, "lentoid bodies", and "micro-lenses". These cells are produced alone or "community-grown" with other ocular tissues. Lentoid bodies/micro-lenses generated from human patients carrying mutations in crystallin genes demonstrate proof-of-principle that these cells are suitable for mechanistic studies of cataractogenesis. Taken together, current and emerging advanced in vitro differentiation methods pave the road to understand molecular mechanisms of cataract formation caused by the entire spectrum of mutations in DNA-binding regulatory genes, such as PAX6, SOX2, FOXE3, MAF, PITX3, and HSF4, individual crystallins, and other genes such as BFSP1, BFSP2, EPHA2, GJA3, GJA8, LIM2, MIP, and TDRD7 represented in human cataract patients.
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Affiliation(s)
- Aleš Cvekl
- Departments Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, NY 10461, USA
- Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Michael John Camerino
- Departments Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, NY 10461, USA
- Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
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26
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Lane EL, Lelos MJ. Defining the unknowns for cell therapies in Parkinson's disease. Dis Model Mech 2022; 15:dmm049543. [PMID: 36165848 PMCID: PMC9555765 DOI: 10.1242/dmm.049543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
First-in-human clinical trials have commenced to test the safety and efficacy of cell therapies for people with Parkinson's disease (PD). Proof of concept that this neural repair strategy is efficacious is based on decades of preclinical studies and clinical trials using primary foetal cells, as well as a significant literature exploring more novel stem cell-derived products. Although several measures of efficacy have been explored, including the successful in vitro differentiation of stem cells to dopamine neurons and consistent alleviation of motor dysfunction in rodent models, many unknowns still remain regarding the long-term clinical implications of this treatment strategy. Here, we consider some of these outstanding questions, including our understanding of the interaction between anti-Parkinsonian medication and the neural transplant, the impact of the cell therapy on cognitive or neuropsychiatric symptoms of PD, the role of neuroinflammation in the therapeutic process and the development of graft-induced dyskinesias. We identify questions that are currently pertinent to the field that require further exploration, and pave the way for a more holistic understanding of this neural repair strategy for treatment of PD.
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Affiliation(s)
- Emma L. Lane
- Cardiff School of Pharmacy and Pharmaceutical Sciences, King Edward VII Avenue, Cardiff University, Cardiff CF10 3NB, UK
| | - Mariah J. Lelos
- School of Biosciences, Museum Avenue, Cardiff University, Cardiff CF10 3AX, UK
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27
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Pochechuev MS, Bilan DS, Fedotov IV, Kelmanson IV, Solotenkov MA, Stepanov EA, Kotova DA, Ivanova AD, Kostyuk AI, Raevskii RI, Lanin AA, Fedotov AB, Belousov VV, Zheltikov AM. Real-time fiber-optic recording of acute-ischemic-stroke signatures. JOURNAL OF BIOPHOTONICS 2022; 15:e202200050. [PMID: 35654757 DOI: 10.1002/jbio.202200050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 04/24/2022] [Accepted: 05/31/2022] [Indexed: 06/15/2023]
Abstract
We present an experimental framework and methodology for in vivo studies on rat stroke models that enable a real-time fiber-optic recording of stroke-induced hydrogen peroxide and pH transients in ischemia-affected brain areas. Arrays of reconnectable implantable fiber probes combined with advanced optogenetic fluorescent protein sensors are shown to enable a quantitative multisite time-resolved study of oxidative-stress and acidosis buildup dynamics as the key markers, correlates and possible drivers of ischemic stroke. The fiber probes designed for this work provide a wavelength-multiplex forward-propagation channel for a spatially localized, dual-pathway excitation of genetically encoded fluorescence-protein sensors along with a back-propagation channel for the fluorescence return from optically driven fluorescence sensors. We show that the spectral analysis of the fiber-probe-collected fluorescence return provides means for a high-fidelity autofluorescence background subtraction, thus enhancing the sensitivity of real-time detection of stroke-induced transients and significantly reducing measurement uncertainties in in vivo acute-stroke studies as inherently statistical experiments operating with outcomes of multiply repeated measurements on large populations of individually variable animal stroke models.
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Affiliation(s)
| | - Dmitry S Bilan
- M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- Pirogov Russian National Research Medical University, Moscow, Russia
| | - Ilya V Fedotov
- Physics Department, M.V. Lomonosov Moscow State University, Moscow, Russia
- Department of Physics and Astronomy, Texas A&M University, College Station, Texas, USA
- Russian Quantum Center, Skolkovo, Moscow, Russia
| | - Ilya V Kelmanson
- M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- Pirogov Russian National Research Medical University, Moscow, Russia
| | - Maxim A Solotenkov
- Physics Department, M.V. Lomonosov Moscow State University, Moscow, Russia
| | - Evgeny A Stepanov
- Physics Department, M.V. Lomonosov Moscow State University, Moscow, Russia
| | - Daria A Kotova
- M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- Pirogov Russian National Research Medical University, Moscow, Russia
| | - Alexandra D Ivanova
- M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
| | - Alexander I Kostyuk
- M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- Pirogov Russian National Research Medical University, Moscow, Russia
| | - Roman I Raevskii
- M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
| | - Aleksandr A Lanin
- Physics Department, M.V. Lomonosov Moscow State University, Moscow, Russia
- Russian Quantum Center, Skolkovo, Moscow, Russia
| | - Andrei B Fedotov
- Physics Department, M.V. Lomonosov Moscow State University, Moscow, Russia
- Russian Quantum Center, Skolkovo, Moscow, Russia
- National University of Science and Technology "MISiS", Moscow, Russia
| | - Vsevolod V Belousov
- M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- Pirogov Russian National Research Medical University, Moscow, Russia
- Federal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, Moscow, Russia
| | - Aleksei M Zheltikov
- Department of Physics and Astronomy, Texas A&M University, College Station, Texas, USA
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28
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Xu X, Feng Q, Ma X, Deng Y, Zhang K, Ooi HS, Yang B, Zhang ZY, Feng B, Bian L. Dynamic gelatin-based hydrogels promote the proliferation and self-renewal of embryonic stem cells in long-term 3D culture. Biomaterials 2022; 289:121802. [PMID: 36152514 DOI: 10.1016/j.biomaterials.2022.121802] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 08/12/2022] [Accepted: 09/09/2022] [Indexed: 11/02/2022]
Abstract
Long-term maintenance of embryonic stem cells (ESCs) in the undifferentiated state is still challenging. Compared with traditional 2D culture methods, 3D culture in biomaterials such as hydrogels is expected to better support the long-term self-renewal of ESCs by emulating the biophysical and biochemical properties of the extracellular matrix (ECM). Although prior studies showed that soft and degradable hydrogels favor the 3D growth of ESCs, few studies have examined the impact of the structural dynamics of the hydrogel matrix on ESC behaviors. Herein, we report a gelatin-based structurally dynamic hydrogel (GelCD hydrogel) that emulates the intrinsic structural dynamics of the ECM. Compared with covalently crosslinked gelatin hydrogels (GelMA hydrogels) with similar stiffness and biodegradability, GelCD hydrogels significantly promote the clonal expansion and viability of encapsulated mouse ESCs (mESCs) independent of MMP-mediated hydrogel degradation. Furthermore, GelCD hydrogels better maintain the pluripotency of encapsulated mESCs than do traditional 2D culture methods that use MEF feeder cells or medium supplementation with GSK3β and MEK 1/2 inhibitors (2i). When cultured in GelCD hydrogels for an extended period (over 2 months) with cell passaging every 7 days, mESCs preserve their normal morphology and maintain their pluripotency and full differentiation capability. Our findings highlight the critical role of the structural dynamics of the hydrogel matrix in accommodating the volume expansion that occurs during clonal ESC growth, and we believe that our dynamic hydrogels represent a valuable tool to support the long-term 3D culture of ESCs.
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Affiliation(s)
- Xiayi Xu
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China.
| | - Qian Feng
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China; Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Chongqing, 400044, China
| | - Xun Ma
- Center for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Chinese Academy of Sciences Limited, Hong Kong SAR, 999077, China; School of Biomedical Sciences, Faculty of Medicine, Institute for Tissue Engineering and Regenerative Medicine (iTERM), CUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
| | - Yingrui Deng
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
| | - Kunyu Zhang
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China; School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, 511442, China
| | - Hon Son Ooi
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
| | - Boguang Yang
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
| | - Zhi-Yong Zhang
- Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou City, Guangdong Province, 510150, China.
| | - Bo Feng
- Center for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Chinese Academy of Sciences Limited, Hong Kong SAR, 999077, China; School of Biomedical Sciences, Faculty of Medicine, Institute for Tissue Engineering and Regenerative Medicine (iTERM), CUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China; Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China.
| | - Liming Bian
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, 511442, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, China; Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, 510006, China; Guangdong Provincial Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou, 510006, China.
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Ceramide and Sphingosine-1-Phosphate in Neurodegenerative Disorders and Their Potential Involvement in Therapy. Int J Mol Sci 2022; 23:ijms23147806. [PMID: 35887154 PMCID: PMC9324343 DOI: 10.3390/ijms23147806] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 07/08/2022] [Accepted: 07/11/2022] [Indexed: 02/04/2023] Open
Abstract
Neurodegenerative disorders (ND) are progressive diseases of the nervous system, often without resolutive therapy. They are characterized by a progressive impairment and loss of specific brain regions and neuronal populations. Cellular and animal model studies have identified several molecular mechanisms that play an important role in the pathogenesis of ND. Among them are alterations of lipids, in particular sphingolipids, that play a crucial role in neurodegeneration. Overall, during ND, ceramide-dependent pro-apoptotic signalling is promoted, whereas levels of the neuroprotective spingosine-1-phosphate are reduced. Moreover, ND are characterized by alterations of the metabolism of complex sphingolipids. The finding that altered sphingolipid metabolism has a role in ND suggests that its modulation might provide a useful strategy to identify targets for possible therapies. In this review, based on the current literature, we will discuss how bioactive sphingolipids (spingosine-1-phosphate and ceramide) are involved in some ND (Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis) and their possible involvement in therapies.
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30
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Zhang J, Liu Y, Liu Y, Liu W, Lu F, Yuan Z, Lu C. Gold Nanocluster-Encapsulated Hyperbranched Polyethyleneimine for Selective and Ratiometric Dopamine Analyses by Enhanced Self-Polymerization. Front Chem 2022; 10:928607. [PMID: 35873048 PMCID: PMC9307107 DOI: 10.3389/fchem.2022.928607] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 05/17/2022] [Indexed: 11/13/2022] Open
Abstract
The exploitation of selective and sensitive dopamine (DA) sensors is essential to more deeply understand its biological function and diagnosis of related diseases. In this study, gold nanocluster-encapsulated hyperbranched polyethyleneimine (hPEI-Au NCs) has been explored as the specific and ratiometric DA nanoprobe through hPEI-assisted DA self-polymerization reactions. The Au NCs encapsulation not only provides a fluorescent internal reference but also enhances the DA self-polymerization by weakening the proton sponge effect of the hPEI layer. Rapid and sensitive DA detection is realized through the proposed hPEI-Au NC nanoprobe with a limit of detection of 10 nM. The favorable selectivity over other possible interferents including amino acids, sugars, and salts is due to the specific self-polymerization reaction. The DA analysis in urine samples with small relative standard deviations has been accomplished with an hPEI-Au NC nanoprobe.
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Affiliation(s)
- Jing Zhang
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, China
| | - Ying Liu
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, China
| | - Yang Liu
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, China
| | - Wencai Liu
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, China
| | - Fengniu Lu
- Department of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, China
| | - Zhiqin Yuan
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, China
- Beijing Key Laboratory of Plant Resources Research and Development, Beijing Technology and Business University, Beijing, China
- *Correspondence: Zhiqin Yuan, ; Chao Lu,
| | - Chao Lu
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, China
- Green Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou, China
- *Correspondence: Zhiqin Yuan, ; Chao Lu,
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Zhang SY, Zhao J, Ni JJ, Li H, Quan ZZ, Qing H. Application and prospects of high-throughput screening for in vitro neurogenesis. World J Stem Cells 2022; 14:393-419. [PMID: 35949394 PMCID: PMC9244953 DOI: 10.4252/wjsc.v14.i6.393] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 04/07/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
Over the past few decades, high-throughput screening (HTS) has made great contributions to new drug discovery. HTS technology is equipped with higher throughput, minimized platforms, more automated and computerized operating systems, more efficient and sensitive detection devices, and rapid data processing systems. At the same time, in vitro neurogenesis is gradually becoming important in establishing models to investigate the mechanisms of neural disease or developmental processes. However, challenges remain in generating more mature and functional neurons with specific subtypes and in establishing robust and standardized three-dimensional (3D) in vitro models with neural cells cultured in 3D matrices or organoids representing specific brain regions. Here, we review the applications of HTS technologies on in vitro neurogenesis, especially aiming at identifying the essential genes, chemical small molecules and adaptive microenvironments that hold great prospects for generating functional neurons or more reproductive and homogeneous 3D organoids. We also discuss the developmental tendency of HTS technology, e.g., so-called next-generation screening, which utilizes 3D organoid-based screening combined with microfluidic devices to narrow the gap between in vitro models and in vivo situations both physiologically and pathologically.
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Affiliation(s)
- Shu-Yuan Zhang
- Key Laboratory of Molecular Medicine and Biotherapy in the Ministry of Industry and Information Technology, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
| | - Juan Zhao
- Aerospace Medical Center, Aerospace Center Hospital, Beijing 100049, China
| | - Jun-Jun Ni
- Key Laboratory of Molecular Medicine and Biotherapy in the Ministry of Industry and Information Technology, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
| | - Hui Li
- Key Laboratory of Molecular Medicine and Biotherapy in the Ministry of Industry and Information Technology, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
| | - Zhen-Zhen Quan
- Key Laboratory of Molecular Medicine and Biotherapy in the Ministry of Industry and Information Technology, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
| | - Hong Qing
- Key Laboratory of Molecular Medicine and Biotherapy in the Ministry of Industry and Information Technology, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
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Wang Q, Zheng K, Zhang W, Li MJ. A sensitive photoluminescent sensor based on highly charged monoruthenium(II) complexes for dopamine detection. J Inorg Biochem 2022; 234:111902. [PMID: 35763905 DOI: 10.1016/j.jinorgbio.2022.111902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 06/01/2022] [Accepted: 06/09/2022] [Indexed: 11/15/2022]
Abstract
A sensitive and selective photoluminescent sensor based on the highly charged monoruthenium(II) complex was designed to detect dopamine (DA) in aqueous samples. Two novel highly charged cationic ruthenium(II) complexes [Ru(bpy)2(bpy-N)]X4 (bpy = 2,2'-bipyridine, bpy-N = 4,4'-bis[N,N,N-triethyl-(methylamino)]-2,2'-bipyridine, X- = [PF6]- (1a) or Cl- (1b) and [Ru(bpy)(bpy-N)2]X6 (X- = [PF6]- (2a) or Cl-(2b)) can be assembled with anionic surfactant sodium dodecylbenzene sulfonate (SDBS), leading to an enhancement of photoluminescence intensity. Upon addition of DA to the system, the photoluminescence intensity of the assembled system was quenched due to the energy transfer effect. It exhibited a wide linear range (0.1-50 μM) and low detection limit (10 nM). The sensor demonstrated a high selectivity toward DA, especially in the presence of adrenaline (Adr) and norepinephrine (NE), whose structures are similar to DA in biological systems. With the merits of simple operation, obvious phenomenon and fast response speed, the sensor had a potential application prospect in human urine sample.
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Affiliation(s)
- Qingqing Wang
- Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, Department of Chemistry, Fuzhou University, Fuzhou 350116, PR China
| | - Kai Zheng
- Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, Department of Chemistry, Fuzhou University, Fuzhou 350116, PR China
| | - Wanqing Zhang
- Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, Department of Chemistry, Fuzhou University, Fuzhou 350116, PR China
| | - Mei-Jin Li
- Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, Department of Chemistry, Fuzhou University, Fuzhou 350116, PR China.
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Liu Y, Liu Y, Zhang J, Zheng J, Yuan Z, Lu C. Catechin-inspired gold nanocluster nanoprobe for selective and ratiometric dopamine detection via forming azamonardine. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2022; 274:121142. [PMID: 35305522 DOI: 10.1016/j.saa.2022.121142] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 03/03/2022] [Accepted: 03/09/2022] [Indexed: 06/14/2023]
Abstract
The sensitive and selective perception of dopamine (DA, a typical neurotransmitter) is important to evaluate the biological environment. In this study, a catechin-functionalized gold nanocluster (C-Au NC) nanoprobe has been explored for the ratiometric DA sensing. The detection mechanism is based on the formation of azamonardine via selective DA-catechin chemical reaction and subsequent enhanced fluorescence emission. Using Au NC emission as the internal reference, ratiometric fluorescence variation is realized, which allows sensitive DA analysis with a limit of detection of 1.0 nM (S/N = 3) and linear response concentration range from 0 to 500 nM. The characteristic chemical reaction between catechin and DA affords favorable selectivity over other amino acids, metal ions and small molecules. In addition, the practical application of the proposed nanoprobe is validated by the accurate detection of DA content in urea and cell lysate samples.
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Affiliation(s)
- Ying Liu
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China
| | - Yang Liu
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China
| | - Jing Zhang
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China
| | - Jiaojiao Zheng
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China
| | - Zhiqin Yuan
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China; Beijing Key Laboratory of Plant Resources Research and Development, Beijing Technology and Business University, Beijing 100048, China.
| | - Chao Lu
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China; Green Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou 450001,China.
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Conjugated polymer nanoparticles and their nanohybrids as smart photoluminescent and photoresponsive material for biosensing, imaging, and theranostics. Mikrochim Acta 2022; 189:83. [PMID: 35118576 DOI: 10.1007/s00604-021-05153-w] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 12/13/2021] [Indexed: 02/06/2023]
Abstract
The emergence of conjugated polymers (CPs) has provided a pathway to attain smart multifunctional conjugated polymer nanoparticles (CPNs) with enhanced properties and diverse applications. CPNs based on π-extended CPs exhibit high fluorescence brightness, low cytotoxicity, excellent photostability, reactive oxygen species (ROS) generation ability, high photothermal conversion efficiency (PCE), etc. which endorse them as an excellent theranostic tool. Furthermore, the unique light-harvesting and energy transfer properties of CPNs enables their transformation into smart functional nanohybrids with augmented performance. Owing to such numerous features, simple preparation method and an easy separation process, the CPNs and their hybrids have been constantly rising as a frontrunner in the domain of medicine and much work has been done in the respective research area. This review summarizes the recent progress that has been made in the field of CPNs for biological and biomedical applications with special emphasis on biosensing, imaging, and theranostics. Following an introduction into the field, a first large section provides overview of the conventional as well as recently established synthetic methods for various types of CPNs. Then, the CPNs-based fluorometric assays for biomolecules based on different detection strategies have been described. Later on, examples of CPNs-based probes for imaging, both in vitro and in vivo using cancer cells and animal models have been explored. The next section highlighted the vital theranostic applications of CPNs and corresponding nanohybrids, mainly via imaging-guided photodynamic therapy (PDT), photothermal therapy (PTT) and drug delivery. The last section summarizes the current challenges and gives an outlook on the potential future trends on CPNs as advanced healthcare material.
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Puranik N, Arukha AP, Yadav SK, Yadav D, Jin JO. Exploring the Role of Stem Cell Therapy in Treating Neurodegenerative Diseases: Challenges and Current Perspectives. Curr Stem Cell Res Ther 2022; 17:113-125. [PMID: 35135462 DOI: 10.2174/1574888x16666210810103838] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 05/18/2021] [Accepted: 06/01/2021] [Indexed: 11/22/2022]
Abstract
:
Several human neurological disorders, such as Parkinson’s disease, Alzheimer’s disease,
amyotrophic lateral sclerosis, Huntington’s disease, spinal cord injury, multiple sclerosis, and brain
stroke, are caused by the injury to neurons or glial cells. The recent years have witnessed the successful
generation of neurons and glia cells driving efforts to develop stem-cell-based therapies for
patients to combat a broad spectrum of human neurological diseases. The inadequacy of suitable
cell types for cell replacement therapy in patients suffering from neurological disorders has hampered
the development of this promising therapeutic approach. Attempts are thus being made to reconstruct
viable neurons and glial cells from different stem cells, such as embryonic stem cells,
mesenchymal stem cells, and neural stem cells. Dedicated research to cultivate stem cell-based
brain transplantation therapies has been carried out. We aim at compiling the breakthroughs in the
field of stem cell-based therapy for the treatment of neurodegenerative maladies, emphasizing the
shortcomings faced, victories achieved, and the future prospects of the therapy in clinical settings.
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Affiliation(s)
- Nidhi Puranik
- Department of Biological Science, Bharathiar University, Coimbatore, Tamil Nadu-641046, India
| | - Ananta Prasad Arukha
- Comparative Diagnostic
and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville- 32608, U.S.A
| | - Shiv Kumar Yadav
- Department of Botany, Government Lal Bahadur Shastri PG college, Sironj, Vidisha, Madhya Pradesh, India
| | - Dhananjay Yadav
- Department of Medical Biotechnology, Yeungnam University, Gyeongsan 712-749, Korea
| | - Jun O. Jin
- Department
of Medical Biotechnology, Yeungnam University, Gyeongsan 712-749, Korea
- Research Institute of Cell Culture, Yeungnam University, Gyeongsan 38541, Korea
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Wang M, Guo H, Wu N, Zhang J, Zhang T, Liu B, Pan Z, Peng L, Yang W. A novel triazine-based covalent organic framework combined with AuNPs and reduced graphene oxide as an electrochemical sensing platform for the simultaneous detection of uric acid, dopamine and ascorbic acid. Colloids Surf A Physicochem Eng Asp 2022. [DOI: 10.1016/j.colsurfa.2021.127928] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Roles of Transcription Factors in the Development and Reprogramming of the Dopaminergic Neurons. Int J Mol Sci 2022; 23:ijms23020845. [PMID: 35055043 PMCID: PMC8775916 DOI: 10.3390/ijms23020845] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 12/31/2021] [Accepted: 01/01/2022] [Indexed: 02/04/2023] Open
Abstract
The meso-diencephalic dopaminergic (mdDA) neurons regulate various critical processes in the mammalian nervous system, including voluntary movement and a wide range of behaviors such as mood, reward, addiction, and stress. mdDA neuronal loss is linked with one of the most prominent human movement neurological disorders, Parkinson’s disease (PD). How these cells die and regenerate are two of the most hotly debated PD research topics. As for the latter, it has been long known that a series of transcription factors (TFs) involves the development of mdDA neurons, specifying cell types and controlling developmental patterns. In vitro and in vivo, TFs regulate the expression of tyrosine hydroxylase, a dopamine transporter, vesicular monoamine transporter 2, and L-aromatic amino acid decarboxylase, all of which are critical for dopamine synthesis and transport in dopaminergic neurons (DA neurons). In this review, we encapsulate the molecular mechanism of TFs underlying embryonic growth and maturation of mdDA neurons and update achievements on dopaminergic cell therapy dependent on knowledge of TFs in mdDA neuronal development. We believe that a deeper understanding of the extrinsic and intrinsic factors that influence DA neurons’ fate and development in the midbrain could lead to a better strategy for PD cell therapy.
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Millman JR, Tan JH, Colton CK. Mouse Pluripotent Stem Cell Differentiation Under Physiological Oxygen Reduces Residual Teratomas. Cell Mol Bioeng 2021; 14:555-567. [PMID: 34900010 DOI: 10.1007/s12195-021-00687-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 06/24/2021] [Indexed: 10/20/2022] Open
Abstract
Introduction Residual pluripotent stem cells (PSC) within differentiated populations are problematic because of their potential to form tumors. Simple methods to reduce their occurrence are needed. Methods Here, we demonstrate that control of the oxygen partial pressure (pO2) to physiological levels typical of the developing embryo, enabled by culture on a highly oxygen permeable substrate, reduces the fraction of PSC within and the tumorigenic potential of differentiated populations. Results Differentiation and/or extended culture at low pO2 reduced measured pluripotency markers by up to four orders of magnitude for mouse PSCs (mPSCs). Combination with cell sorting increased the reduction to as much as six orders of magnitude. Upon implantation into immunocompromised mice, mPSCs differentiated at low pO2 either did not form tumors or formed tumors at a slower rate than at high pO2. Conclusions Low pO2 culture alone or in combination with other methods is a potentially straightforward method that could be applied to future cell therapy protocols to minimize the possibility of tumor formation.
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Affiliation(s)
- Jeffrey R Millman
- Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110 USA.,Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130 USA
| | - Jit Hin Tan
- Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139 USA
| | - Clark K Colton
- Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139 USA
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Ahmad J, Haider N, Khan MA, Md S, Alhakamy NA, Ghoneim MM, Alshehri S, Sarim Imam S, Ahmad MZ, Mishra A. Novel therapeutic interventions for combating Parkinson's disease and prospects of Nose-to-Brain drug delivery. Biochem Pharmacol 2021; 195:114849. [PMID: 34808125 DOI: 10.1016/j.bcp.2021.114849] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 11/16/2021] [Accepted: 11/17/2021] [Indexed: 02/06/2023]
Abstract
Parkinson disease (PD) is a progressive neurodegenerative disorder prevalent mainly in geriatric population. While, L-DOPA remains one of the major choices for the therapeutic management of PD, various motor and non-motor manifestations complicate the management of PD. In the last two decades, exhaustive research has been carried out to explore novel therapeutic approaches for mitigating motor and non-motor symptoms of PD. These approaches majorly include receptor-based, anti-inflammatory, stem-cell and nucleic acid based. The major limitations of existing therapeutic interventions (of commonly oral route) are low efficacy due to low brain bioavailability and associated side effects. Nanotechnology has been exploited and has gained wide attention in the recent years as an approach for enhancement of bioavailability of various small molecule drugs in the brain. To address the challenges associated with PD therapy, nose-to-brain delivery utilizing nanomedicine-based approaches has been found to be encouraging in published evidence. Therefore, the present work summarises the major challenges and limitations with antiparkinsonian drugs, novel therapeutic interventions, and scope of nanomedicine-based nose-to-brain delivery in addressing the current challenges of antiparkinsonian therapy. The manuscript tries to sensitize the researchers for designing brain-targeted nanomedicine loaded with natural/synthetic scaffolds, biosimilars, and nucleic acids that can bypass the first-pass effect for the effective management of PD.
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Affiliation(s)
- Javed Ahmad
- Department of Pharmaceutics, College of Pharmacy, Najran University, Najran 11001, Saudi Arabia.
| | - Nafis Haider
- Prince Sultan Military College of Health Sciences, Dhahran 34313, Saudi Arabia.
| | - Mohammad Ahmed Khan
- Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
| | - Shadab Md
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
| | - Nabil A Alhakamy
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
| | - Mohammed M Ghoneim
- Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia.
| | - Sultan Alshehri
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
| | - Syed Sarim Imam
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
| | - Mohammad Zaki Ahmad
- Department of Pharmaceutics, College of Pharmacy, Najran University, Najran 11001, Saudi Arabia.
| | - Awanish Mishra
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER) - Guwahati, Changsari, Kamrup Assam-781101, India.
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40
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Song H, Liu Y, Fang Y, Zhang D. Carbon-Based Electrochemical Sensors for In Vivo and In Vitro Neurotransmitter Detection. Crit Rev Anal Chem 2021; 53:955-974. [PMID: 34752170 DOI: 10.1080/10408347.2021.1997571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/21/2023]
Abstract
As essential neurological chemical messengers, neurotransmitters play an integral role in the maintenance of normal mammalian physiology. Aberrant neurotransmitter activity is associated with a range of neurological conditions including Parkinson's disease, Alzheimer's disease, and Huntington's disease. Many studies to date have tested different approaches to detecting neurotransmitters, yet the detection of these materials within the brain, due to the complex environment of the brain and the rapid metabolism of neurotransmitters, remains challenging and an area of active research. There is a clear need for the development of novel neurotransmitter sensing technologies capable of rapidly and sensitively monitoring specific analytes within the brain without adversely impacting the local microenvironment in which they are implanted. Owing to their excellent sensitivity, portability, ease-of-use, amenability to microprocessing, and low cost, electrochemical sensors methods have been widely studied in the context of neurotransmitter monitoring. The present review, thus, surveys current progress in this research field, discussing developed electrochemical neurotransmitter sensors capable of detecting dopamine (DA), serotonin (5-HT), acetylcholine (Ach), glutamate (Glu), nitric oxide (NO), adenosine (ADO), and so on. Of these technologies, those based on carbon nanostructures-modified electrodes including carbon nanotubes (CNTs), graphene (GR), gaphdiyne (GDY), carbon nanofibers (CNFs), and derivatives thereof hold particular promise owing to their excellent biocompatibility and electrocatalytic performance. The continued development of these and related technologies is, thus, likely to lead to major advances in the clinical diagnosis of neurological diseases and the detection of novel biomarkers thereof.
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Affiliation(s)
- Huijun Song
- Research Center of Experimental Acupuncture Science, College of Acumox and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin, PR China
| | - Yangyang Liu
- Research Center of Experimental Acupuncture Science, College of Acumox and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin, PR China
| | - Yuxin Fang
- Research Center of Experimental Acupuncture Science, College of Acumox and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin, PR China
| | - Di Zhang
- College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, PR China
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Guerra-Crespo M, Collazo-Navarrete O, Ramos-Acevedo R, Morato-Torres CA, Schüle B. Embryoid Body Formation from Mouse and Human Pluripotent Stem Cells for Transplantation to Study Brain Microenvironment and Cellular Differentiation. METHODS IN MOLECULAR BIOLOGY (CLIFTON, N.J.) 2021; 2520:215-232. [PMID: 34611820 DOI: 10.1007/7651_2021_433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Human embryonic stem cell (hESC) and human-induced pluripotent stem cell (hiPSC) technologies have a critical role in regenerative strategies for personalized medicine. Both share the ability to differentiate into almost any cell type of the human body. The study of their properties and clinical applications requires the development of robust and reproducible cell culture paradigms that direct cell differentiation toward a specific phenotype in vitro and in vivo. Our group evaluated the potential of mouse ESCs (mESCs), hESCs, and hiPSCs (collectively named pluripotent stem cells, PSCs) to analyze brain microenvironments through the use of embryoid body (EB)-derived cells from these cell sources. EB are cell aggregates in 3D culture conditions that recapitulate embryonic development. Our approach focuses on studying the midbrain dopaminergic phenotype and transplanting EB into the substantia nigra pars compacta (SNpc) in a Parkinson's disease rodent model. Here, we describe cell culture protocols for EB generation from PSCs that show significant in vivo differentiation toward dopaminergic neurons.
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Affiliation(s)
- Magdalena Guerra-Crespo
- Instituto de Fisiología Celular, División de Neurociencias, Universidad Nacional Autónoma de México, Mexico City, Mexico.
- Laboratorio de Medicina Regenerativa, Departamento de Cirugía, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
| | - Omar Collazo-Navarrete
- Laboratorio Nacional de Recursos Genómicos, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Rodrigo Ramos-Acevedo
- Instituto de Fisiología Celular, División de Neurociencias, Universidad Nacional Autónoma de México, Mexico City, Mexico
- Laboratorio de Medicina Regenerativa, Departamento de Cirugía, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Carmen Alejandra Morato-Torres
- Instituto de Fisiología Celular, División de Neurociencias, Universidad Nacional Autónoma de México, Mexico City, Mexico
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
| | - Birgitt Schüle
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
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Kim IK, Park JH, Kim B, Hwang KC, Song BW. Recent advances in stem cell therapy for neurodegenerative disease: Three dimensional tracing and its emerging use. World J Stem Cells 2021; 13:1215-1230. [PMID: 34630859 PMCID: PMC8474717 DOI: 10.4252/wjsc.v13.i9.1215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 05/20/2021] [Accepted: 08/30/2021] [Indexed: 02/06/2023] Open
Abstract
Neurodegenerative disease is a brain disorder caused by the loss of structure and function of neurons that lowers the quality of human life. Apart from the limited potential for endogenous regeneration, stem cell-based therapies hold considerable promise for maintaining homeostatic tissue regeneration and enhancing plasticity. Despite many studies, there remains insufficient evidence for stem cell tracing and its correlation with endogenous neural cells in brain tissue with three-dimensional structures. Recent advancements in tissue optical clearing techniques have been developed to overcome the existing shortcomings of cross-sectional tissue analysis in thick and complex tissues. This review focuses on recent progress of stem cell treatments to improve neurodegenerative disease, and introduces tissue optical clearing techniques that can implement a three-dimensional image as a proof of concept. This review provides a more comprehensive understanding of stem cell tracing that will play an important role in evaluating therapeutic efficacy and cellular interrelationship for regeneration in neurodegenerative diseases.
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Affiliation(s)
- Il-Kwon Kim
- Institute for Bio-Medical Convergence, Catholic Kwandong University International St. Mary’s Hospital, Incheon Metropolitan City 22711, South Korea
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangwon-do 25601, South Korea
| | - Jun-Hee Park
- Institute for Bio-Medical Convergence, Catholic Kwandong University International St. Mary’s Hospital, Incheon Metropolitan City 22711, South Korea
| | - Bomi Kim
- Institute for Bio-Medical Convergence, Catholic Kwandong University International St. Mary’s Hospital, Incheon Metropolitan City 22711, South Korea
| | - Ki-Chul Hwang
- Institute for Bio-Medical Convergence, Catholic Kwandong University International St. Mary’s Hospital, Incheon Metropolitan City 22711, South Korea
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangwon-do 25601, South Korea
| | - Byeong-Wook Song
- Institute for Bio-Medical Convergence, Catholic Kwandong University International St. Mary’s Hospital, Incheon Metropolitan City 22711, South Korea
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangwon-do 25601, South Korea.
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Katunin P, Zhou J, Shehata OM, Peden AA, Cadby A, Nikolaev A. An Open-Source Framework for Automated High-Throughput Cell Biology Experiments. Front Cell Dev Biol 2021; 9:697584. [PMID: 34631697 PMCID: PMC8498207 DOI: 10.3389/fcell.2021.697584] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 08/19/2021] [Indexed: 12/12/2022] Open
Abstract
Modern data analysis methods, such as optimization algorithms or deep learning have been successfully applied to a number of biotechnological and medical questions. For these methods to be efficient, a large number of high-quality and reproducible experiments needs to be conducted, requiring a high degree of automation. Here, we present an open-source hardware and low-cost framework that allows for automatic high-throughput generation of large amounts of cell biology data. Our design consists of an epifluorescent microscope with automated XY stage for moving a multiwell plate containing cells and a perfusion manifold allowing programmed application of up to eight different solutions. Our system is very flexible and can be adapted easily for individual experimental needs. To demonstrate the utility of the system, we have used it to perform high-throughput Ca2+ imaging and large-scale fluorescent labeling experiments.
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Affiliation(s)
- Pavel Katunin
- Fresco Labs, London, United Kingdom
- Information Technologies and Programming Faculty, ITMO University, St. Petersburg, Russia
| | - Jianbo Zhou
- Department of Biomedical Sciences, University of Sheffield, Sheffield, United Kingdom
| | - Ola M Shehata
- Department of Biomedical Sciences, University of Sheffield, Sheffield, United Kingdom
| | - Andrew A Peden
- Department of Biomedical Sciences, University of Sheffield, Sheffield, United Kingdom
| | - Ashley Cadby
- Department of Physics and Astronomy, University of Sheffield, Sheffield, United Kingdom
| | - Anton Nikolaev
- Department of Biomedical Sciences, University of Sheffield, Sheffield, United Kingdom
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Behl T, Kaur I, Kumar A, Mehta V, Zengin G, Arora S. Gene Therapy in the Management of Parkinson's Disease: Potential of GDNF as a Promising Therapeutic Strategy. Curr Gene Ther 2021; 20:207-222. [PMID: 32811394 DOI: 10.2174/1566523220999200817164051] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 06/14/2020] [Accepted: 07/15/2020] [Indexed: 12/13/2022]
Abstract
The limitations of conventional treatment therapies in Parkinson's disorder, a common neurodegenerative disorder, lead to the development of an alternative gene therapy approach. Multiple treatment options targeting dopaminergic neuronal regeneration, production of enzymes linked with dopamine synthesis, subthalamic nucleus neurons, regulation of astrocytes and microglial cells and potentiating neurotrophic factors, were established. Viral vector-based dopamine delivery, prodrug approaches, fetal ventral mesencephalon tissue transplantation and dopamine synthesizing enzyme encoding gene delivery are significant therapies evidently supported by numerous trials. The review primarily elaborates on the significant role of glial cell-line derived neurotrophic factor in alleviating motor symptoms and the loss of dopaminergic neurons in Parkinson's disease. Neuroprotective and neuroregenerative effects of GDNF were established via preclinical and clinical study outcomes. The binding of GDNF family ligands with associated receptors leads to the formation of a receptor-ligand complex activating Ret receptor of tyrosine kinase family, which is only expressed in dopaminergic neurons, playing an important role in Parkinson's disease, via its association with the essential protein encoded genes. Furthermore, the review establishes delivery aspects, like ventricular delivery of recombinant GDNF, intraparenchymal and intraputaminal delivery using infusion catheters. The review highlights problems and challenges of GDNF delivery, and essential measures to overcome them, like gene therapy combinations, optimization of delivery vectors, newer targeting devices, motor symptoms curbing focused ultrasound techniques, modifications in patient selection criteria and development of novel delivery strategies based on liposomes and encapsulated cells, to promote safe and effective delivery of neurotrophic factor and establishment of routine treatment therapy for patients.
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Affiliation(s)
- Tapan Behl
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Ishnoor Kaur
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Arun Kumar
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | | | - Gokhan Zengin
- Department of Biology, Faculty of Science, Selcuk University Campus, Konya, Turkey
| | - Sandeep Arora
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
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Bicer A, Ercin BS, Gürler T, Yiğittürk G, Uyanikgil Y, Cetin EO. Possibility of Taking an Offensive Stance in Extravasation Injury: Effects of Fat Injection in Vesicant (Doxorubicin) Induced Skin Necrosis Model in Rats. J INVEST SURG 2021; 35:801-808. [PMID: 34402353 DOI: 10.1080/08941939.2021.1966142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Extravasation injuries are one of the most feared complications of intravenous drug administration. The most common drugs associated with extravasation injury include chemotherapy agents and contrast media. Natural course of vesicant extravasation is discomfort, pain, swelling, inflammation, and ultimately skin ulceration. While diligence is the principle approach in prevention, immediate bed-side measures are as important in controlling the extent of tissue damage. Various options, either medical or interventional are next steps in treatment of the condition including antidotes, volume dilution, flushing, suction, hyperbaric oxygen therapy, and surgery. MATERIALS AND METHODS 12 male Wistar albino rats were divided into two groups; one group received fat injections following subdermal doxorubicin infiltration in their right thighs, while other group received saline injection following subdermal doxorubicin infiltration in their right thighs for dilution. Left thighs of both groups were left untreated following subdermal doxorubicin infiltration. Total area of necrosis, as well as resultant epidermal thicknesses were assessed. Histological analyses were conducted using modified Verhofstad scoring system for comparison. RESULTS Mean necrotic area was significantly smaller in the fat injection group compared to other groups. Median Verhofstad score was lesser in the fat injection group as well. Median epidermal thickness, on the other hand, was greater in the fat injection group. CONCLUSION Injection of fat grafts following vesicant extravasation might be beneficial in preventing the progression of tissue damage, if employed early.
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Affiliation(s)
- Ahmet Bicer
- Department of Plastic Surgery, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Burak Sercan Ercin
- Department of Plastic, Reconstructive and Aesthetic surgery, Bahcesehir University, Istanbul, Turkey.,Department of Plastic, Reconstructive and Aesthetic surgery, Medicalpark Pendik Hospital, Istanbul, Turkey
| | - Tahir Gürler
- Department of Plastic Surgery, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Gürkan Yiğittürk
- Department of Histology and Embryology, Faculty of Medicine, Mugla Sitki Kocman University, Mugla, Turkey
| | - Yigit Uyanikgil
- Department of Histology and Embryology, Faculty of Medicine, Ege University, Izmir, Turkey.,Department of Stem Cell, Ege University, Health Science Institue, Izmir, Turkey.,Cord Blood, Cell and Tissue Research and Application Centre, Ege University, Izmir, Turkey
| | - Emel Oyku Cetin
- Department of Pharmaceutical Technology, Department of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, Ege University, Izmir, Turkey
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Aishwarya L, Arun D, Kannan S. Stem cells as a potential therapeutic option for treating neurodegenerative diseases. Curr Stem Cell Res Ther 2021; 17:590-605. [PMID: 35135464 DOI: 10.2174/1574888x16666210810105136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/27/2021] [Accepted: 06/01/2021] [Indexed: 11/22/2022]
Abstract
In future, neurodegenerative diseases will take over cancer's place and become the major cause of death in the world, especially in developed countries. Advancements in the medical field and its facilities have led to an increase in the old age population, and thus contributing to the increase in number of people suffering from neurodegenerative diseases. Economically it is of a great burden to society and the affected family. No current treatment aims to replace, protect, and regenerate lost neurons; instead, it alleviates the symptoms, extends the life span by a few months and creates severe side effects. Moreover, people who are affected are physically dependent for performing their basic activities, which makes their life miserable. There is an urgent need for therapy that could be able to overcome the deficits of conventional therapy for neurodegenerative diseases. Stem cells, the unspecialized cells with the properties of self-renewing and potency to differentiate into various cells types can become a potent therapeutic option for neurodegenerative diseases. Stem cells have been widely used in clinical trials to evaluate their potential in curing different types of ailments. In this review, we discuss the various types of stem cells and their potential use in the treatment of neurodegenerative disease based on published preclinical and clinical studies.
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Affiliation(s)
- Aishwarya L
- Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai-600 116. India
| | - Dharmarajan Arun
- Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai-600 116. India
| | - Suresh Kannan
- Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai-600 116. India
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Trudler D, Ghatak S, Lipton SA. Emerging hiPSC Models for Drug Discovery in Neurodegenerative Diseases. Int J Mol Sci 2021; 22:8196. [PMID: 34360966 PMCID: PMC8347370 DOI: 10.3390/ijms22158196] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/26/2021] [Accepted: 07/27/2021] [Indexed: 12/12/2022] Open
Abstract
Neurodegenerative diseases affect millions of people worldwide and are characterized by the chronic and progressive deterioration of neural function. Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), represent a huge social and economic burden due to increasing prevalence in our aging society, severity of symptoms, and lack of effective disease-modifying therapies. This lack of effective treatments is partly due to a lack of reliable models. Modeling neurodegenerative diseases is difficult because of poor access to human samples (restricted in general to postmortem tissue) and limited knowledge of disease mechanisms in a human context. Animal models play an instrumental role in understanding these diseases but fail to comprehensively represent the full extent of disease due to critical differences between humans and other mammals. The advent of human-induced pluripotent stem cell (hiPSC) technology presents an advantageous system that complements animal models of neurodegenerative diseases. Coupled with advances in gene-editing technologies, hiPSC-derived neural cells from patients and healthy donors now allow disease modeling using human samples that can be used for drug discovery.
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Affiliation(s)
- Dorit Trudler
- Neurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; (D.T.); (S.G.)
| | - Swagata Ghatak
- Neurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; (D.T.); (S.G.)
| | - Stuart A. Lipton
- Neurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; (D.T.); (S.G.)
- Department of Neurosciences, University of California San Diego School of Medicine, La Jolla, CA 92093, USA
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von Linstow CU, DeLano-Taylor M, Kordower JH, Brundin P. Does Developmental Variability in the Number of Midbrain Dopamine Neurons Affect Individual Risk for Sporadic Parkinson's Disease? JOURNAL OF PARKINSONS DISEASE 2021; 10:405-411. [PMID: 31958098 PMCID: PMC7242832 DOI: 10.3233/jpd-191877] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Parkinson’s disease (PD) is a slowly progressing neurodegenerative disorder that is coupled to both widespread protein aggregation and to loss of substantia nigra dopamine (DA) neurons, resulting in a wide variety of motor and non-motor signs and symptoms. Recent findings suggest that the PD process is triggered several years before there is sufficient degeneration of DA neurons to cause onset of overt motor symptoms. According to this concept, the number of DA neurons present in the substantia nigra at birth could influence the time from the molecular triggering event until the clinical diagnosis with lower number of neurons at birth increasing the risk to develop the disease. Conversely, the risk for diagnosis would be reduced if the number of DA neurons is high at birth. In this commentary, we discuss the genetic and epigenetic factors that might influence the number of nigral DA neurons that each individual is born with and how these may be linked to PD risk.
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Affiliation(s)
| | - Merritt DeLano-Taylor
- Center for Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA.,Department of Biomedical Sciences, Grand Valley State University, Allendale, MI, USA
| | - Jeffrey H Kordower
- Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA
| | - Patrik Brundin
- Center for Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA
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Brambach M, Ernst A, Nolbrant S, Drouin-Ouellet J, Kirkeby A, Parmar M, Olariu V. Neural tube patterning: from a minimal model for rostrocaudal patterning toward an integrated 3D model. iScience 2021; 24:102559. [PMID: 34142058 PMCID: PMC8184516 DOI: 10.1016/j.isci.2021.102559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 04/16/2021] [Accepted: 05/14/2021] [Indexed: 10/27/2022] Open
Abstract
Rostrocaudal patterning of the neural tube is a defining event in vertebrate brain development. This process is driven by morphogen gradients which specify the fate of neural progenitor cells, leading to the partitioning of the tube. Although this is extensively studied experimentally, an integrated view of the genetic circuitry is lacking. Here, we present a minimal gene regulatory model for rostrocaudal patterning, whose tristable topology was determined in a data-driven way. Using this model, we identified the repression of hindbrain fate as promising strategy for the improvement of current protocols for the generation of dopaminergic neurons. Furthermore, we combined our model with an established minimal model for dorsoventral patterning on a realistic 3D neural tube and found that key features of neural tube patterning could be recapitulated. Doing so, we demonstrate how data and models from different sources can be combined to simulate complex in vivo processes.
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Affiliation(s)
- Max Brambach
- Computational Biology and Biological Physics, Department of Astronomy and Theoretical Physics, Lund University, Lund, 223 63, Sweden
| | - Ariane Ernst
- Computational Biology and Biological Physics, Department of Astronomy and Theoretical Physics, Lund University, Lund, 223 63, Sweden
| | - Sara Nolbrant
- Departments of Experimental Medical Science and Clinical Sciences, Wallenberg Neuroscience Center, and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden
| | | | - Agnete Kirkeby
- Departments of Experimental Medical Science and Clinical Sciences, Wallenberg Neuroscience Center, and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden
| | - Malin Parmar
- Departments of Experimental Medical Science and Clinical Sciences, Wallenberg Neuroscience Center, and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden
| | - Victor Olariu
- Computational Biology and Biological Physics, Department of Astronomy and Theoretical Physics, Lund University, Lund, 223 63, Sweden
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Iacovitti L. On the Road from Phenotypic Plasticity to Stem Cell Therapy. J Neurosci 2021; 41:5331-5337. [PMID: 33958488 PMCID: PMC8221603 DOI: 10.1523/jneurosci.0340-21.2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 04/18/2021] [Accepted: 04/27/2021] [Indexed: 11/21/2022] Open
Abstract
In 1981, I published a paper in the first issue of The Journal of Neuroscience with my postdoctoral mentor, Richard Bunge. At that time, the long-standing belief that each neuron expressed only one neurotransmitter, known as Dale's Principle (Dale, 1935), was being hotly debated following a report by French embryologist Nicole Le Douarin showing that neural crest cells destined for one transmitter phenotype could express characteristics of another if transplanted to alternate sites in the developing embryo (Le Douarin, 1980). In the Bunge laboratory, we were able to more directly test the question of phenotypic plasticity in the controlled environment of the tissue culture dish. Thus, in our paper, we grew autonomic catecholaminergic neurons in culture under conditions which promoted the acquisition of cholinergic traits and showed that cells did not abandon their inherited phenotype to adopt a new one but instead were capable of dual transmitter expression. In this Progressions article, I detail the path that led to these findings and how this study impacted the direction I followed for the next 40 years. This is my journey from phenotypic plasticity to the promise of a stem cell therapy.
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Affiliation(s)
- Lorraine Iacovitti
- Department of Neuroscience, Director, Jefferson Stem Cell and Regenerative Neuroscience Center, Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, Pennsylvania 19107
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