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Gotoh S, Kawabori M, Fujimura M. Intranasal administration of stem cell-derived exosomes for central nervous system diseases. Neural Regen Res 2024; 19:1249-1255. [PMID: 37905871 PMCID: PMC11467946 DOI: 10.4103/1673-5374.385875] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 08/21/2023] [Accepted: 09/04/2023] [Indexed: 11/02/2023] Open
Abstract
ABSTRACT Exosomes, lipid bilayer-enclosed small cellular vesicles, are actively secreted by various cells and play crucial roles in intercellular communication. These nanosized vesicles transport internalized proteins, mRNA, miRNA, and other bioactive molecules. Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders. These exosomes exhibit multifaceted properties including anti-apoptotic, anti-inflammatory, neurogenic, and vasculogenic effects. Furthermore, exosomes offer several advantages over stem cell therapy, such as high preservation capacity, low immunogenicity, the ability to traverse the blood-brain barrier, and the potential for drug encapsulation. Consequently, researchers have turned their attention to exosomes as a novel therapeutic avenue. Nonetheless, akin to the limitations of stem cell treatment, the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application. To overcome this hurdle, intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system. By exploiting the olfactory and trigeminal nerve axons, this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier. Notably, exosomes, owing to their small size, can readily access the nerve pathways using this method. As a result, intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosome-based treatments. In this comprehensive review, we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases. Furthermore, we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.
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Affiliation(s)
- Shuho Gotoh
- Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
| | - Masahito Kawabori
- Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
| | - Miki Fujimura
- Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
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Arakawa M, Sakamoto Y, Miyagawa Y, Nito C, Takahashi S, Nitahara-Kasahara Y, Suda S, Yamazaki Y, Sakai M, Kimura K, Okada T. iPSC-derived mesenchymal stem cells attenuate cerebral ischemia-reperfusion injury by inhibiting inflammatory signaling and oxidative stress. Mol Ther Methods Clin Dev 2023; 30:333-349. [PMID: 37637385 PMCID: PMC10448333 DOI: 10.1016/j.omtm.2023.07.005] [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: 07/21/2022] [Accepted: 07/11/2023] [Indexed: 08/29/2023]
Abstract
Induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) hold great promise as a cell source for transplantation into injured tissues to alleviate inflammation. However, the therapeutic efficacy of iMSC transplantation for ischemic stroke remains unknown. In this study, we evaluated the therapeutic effects of iMSC transplantation on brain injury after ischemia-reperfusion using a rat transient middle cerebral artery occlusion model and compared its therapeutic efficacy with that of bone marrow mesenchymal stem cells (BMMSCs). We showed that iMSCs and BMMSCs reduced infarct volumes after reperfusion and significantly improved motor function on days 3, 7, 14, 28, and 56 and cognitive function on days 28 and 56 after reperfusion compared with the vehicle group. Furthermore, immunological analyses revealed that transplantation of iMSCs and BMMSCs inhibited microglial activation and expression of proinflammatory cytokines and suppressed oxidative stress and neuronal cell death in the cerebral cortex at the ischemic border zone. No difference in therapeutic effect was observed between the iMSC and BMMSC groups. Taken together, our results demonstrate that iMSC therapy can be a practical alternative as a cell source for attenuation of brain injury and improvement of neurological function because of the unlimited supply of uniform therapeutic cells.
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Affiliation(s)
- Masafumi Arakawa
- Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
- Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Yuki Sakamoto
- Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Yoshitaka Miyagawa
- Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Chikako Nito
- Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
- Laboratory for Clinical Research, Collaborative Research Center, Nippon Medical School, Tokyo, Japan
| | - Shiro Takahashi
- Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
- Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Yuko Nitahara-Kasahara
- Division of Molecular and Medical Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Satoshi Suda
- Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Yoshiyuki Yamazaki
- Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Mashito Sakai
- Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Kazumi Kimura
- Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Takashi Okada
- Division of Molecular and Medical Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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Yan Y, Wang X, Zhu G. Endometrium Derived Stem Cells as Potential Candidates in Nervous System Repair. Ann Biomed Eng 2022; 50:485-498. [PMID: 35235077 DOI: 10.1007/s10439-022-02909-0] [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: 08/30/2021] [Accepted: 01/01/2022] [Indexed: 11/24/2022]
Abstract
Limited cell division and lack of endogenous repair mechanisms in the central nervous system, hampers tissue repair following neurodegenerative diseases or tissue injuries. Unlike central nervous system; peripheral nervous system has some capacity to repair after injury, but in case of critical sized defects the use of supporting cells in the neural guidance channels seems inevitable to obtain a satisfactory functional recovery. Stem cell therapies have provided new frontiers in the repair of nervous system largely through paracrine secretion mechanisms. The therapeutic potential of stem cells differs according to their tissue of origin, mode of isolation, administration route, and passage number. During the past decades, studies have been focused on stem cells harvested from disposable tissues such as menstrual blood or biopsies from endometrium. These cells are characterized by their high differentiation and proliferation potential, ease of harvest, and lack of ethical concerns. In the current review, we will discuss the prospects and challenges of endometrial stem cells' application in nervous system repair.
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Affiliation(s)
- Yifen Yan
- Department of Gynecology, Renmin Hospital, Hubei University of Medicine, Maojian District, No. 39, Chaoyang Zhong Road, Shiyan City, 442000, Hubei Province, China
| | - Xiaoli Wang
- Department of Gynecology, Renmin Hospital, Hubei University of Medicine, Maojian District, No. 39, Chaoyang Zhong Road, Shiyan City, 442000, Hubei Province, China
| | - Guijuan Zhu
- Department of Gynecology, Renmin Hospital, Hubei University of Medicine, Maojian District, No. 39, Chaoyang Zhong Road, Shiyan City, 442000, Hubei Province, China.
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Rahman MM, Islam MR, Islam MT, Harun-Or-Rashid M, Islam M, Abdullah S, Uddin MB, Das S, Rahaman MS, Ahmed M, Alhumaydhi FA, Emran TB, Mohamed AAR, Faruque MRI, Khandaker MU, Mostafa-Hedeab G. Stem Cell Transplantation Therapy and Neurological Disorders: Current Status and Future Perspectives. BIOLOGY 2022; 11:147. [PMID: 35053145 PMCID: PMC8772847 DOI: 10.3390/biology11010147] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 12/26/2021] [Accepted: 12/29/2021] [Indexed: 02/07/2023]
Abstract
Neurodegenerative diseases are a global health issue with inadequate therapeutic options and an inability to restore the damaged nervous system. With advances in technology, health scientists continue to identify new approaches to the treatment of neurodegenerative diseases. Lost or injured neurons and glial cells can lead to the development of several neurological diseases, including Parkinson's disease, stroke, and multiple sclerosis. In recent years, neurons and glial cells have successfully been generated from stem cells in the laboratory utilizing cell culture technologies, fueling efforts to develop stem cell-based transplantation therapies for human patients. When a stem cell divides, each new cell has the potential to either remain a stem cell or differentiate into a germ cell with specialized characteristics, such as muscle cells, red blood cells, or brain cells. Although several obstacles remain before stem cells can be used for clinical applications, including some potential disadvantages that must be overcome, this cellular development represents a potential pathway through which patients may eventually achieve the ability to live more normal lives. In this review, we summarize the stem cell-based therapies that have been explored for various neurological disorders, discuss the potential advantages and drawbacks of these therapies, and examine future directions for this field.
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Affiliation(s)
- Mohammad Mominur Rahman
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh; (M.M.R.); (M.R.I.); (M.T.I.); (M.H.-O.-R.); (M.I.); (M.B.U.); (S.D.); (M.S.R.); (M.A.)
| | - Mohammad Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh; (M.M.R.); (M.R.I.); (M.T.I.); (M.H.-O.-R.); (M.I.); (M.B.U.); (S.D.); (M.S.R.); (M.A.)
| | - Mohammad Touhidul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh; (M.M.R.); (M.R.I.); (M.T.I.); (M.H.-O.-R.); (M.I.); (M.B.U.); (S.D.); (M.S.R.); (M.A.)
| | - Mohammad Harun-Or-Rashid
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh; (M.M.R.); (M.R.I.); (M.T.I.); (M.H.-O.-R.); (M.I.); (M.B.U.); (S.D.); (M.S.R.); (M.A.)
| | - Mahfuzul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh; (M.M.R.); (M.R.I.); (M.T.I.); (M.H.-O.-R.); (M.I.); (M.B.U.); (S.D.); (M.S.R.); (M.A.)
| | - Sabirin Abdullah
- Space Science Center, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia;
| | - Mohammad Borhan Uddin
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh; (M.M.R.); (M.R.I.); (M.T.I.); (M.H.-O.-R.); (M.I.); (M.B.U.); (S.D.); (M.S.R.); (M.A.)
| | - Sumit Das
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh; (M.M.R.); (M.R.I.); (M.T.I.); (M.H.-O.-R.); (M.I.); (M.B.U.); (S.D.); (M.S.R.); (M.A.)
| | - Mohammad Saidur Rahaman
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh; (M.M.R.); (M.R.I.); (M.T.I.); (M.H.-O.-R.); (M.I.); (M.B.U.); (S.D.); (M.S.R.); (M.A.)
| | - Muniruddin Ahmed
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh; (M.M.R.); (M.R.I.); (M.T.I.); (M.H.-O.-R.); (M.I.); (M.B.U.); (S.D.); (M.S.R.); (M.A.)
| | - Fahad A. Alhumaydhi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 52571, Saudi Arabia;
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
| | | | | | - Mayeen Uddin Khandaker
- Centre for Applied Physics and Radiation Technologies, School of Engineering and Technology, Sunway University, Bandar Sunway 47500, Selangor, Malaysia;
| | - Gomaa Mostafa-Hedeab
- Pharmacology Department & Health Sciences Research Unit, Medical College, Jouf University, Sakaka 72446, Saudi Arabia;
- Pharmacology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef 62521, Egypt
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Hassani N, Taurin S, Alshammary S. Meta-Analysis: The Clinical Application of Autologous Adult Stem Cells in the Treatment of Stroke. Stem Cells Cloning 2021; 14:81-91. [PMID: 35002259 PMCID: PMC8721025 DOI: 10.2147/sccaa.s344943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 11/30/2021] [Indexed: 12/03/2022] Open
Abstract
Introduction Stroke is a leading cause of death and disability worldwide. The disease is caused by reduced blood flow into the brain resulting in the sudden death of neurons. Limited spontaneous recovery might occur after stroke or brain injury, stem cell-based therapies have been used to promote these processes as there are no drugs currently on the market to promote brain recovery or neurogenesis. Adult stem cells (ASCs) have shown the ability of differentiation and regeneration and are well studied in literature. ASCs have also demonstrated safety in clinical application and, therefore, are currently being investigated as a promising alternative intervention for the treatment of stroke. Methods Eleven studies have been systematically selected and reviewed to determine if autologous adult stem cells are effective in the treatment of stroke. Collectively, 368 patients were enrolled across the 11 trials, out of which 195 received stem cell transplantation and 173 served as control. Using data collected from the clinical outcomes, a broad comparison and a meta-analysis were conducted by comparing studies that followed a similar study design. Results Improvement in patients’ clinical outcomes was observed. However, the overall results showed no clinical significance in patients transplanted with stem cells than the control population. Conclusion Most of the trials were early phase studies that focused on safety rather than efficacy. Stem cells have demonstrated breakthrough results in the field of regenerative medicine. Therefore, study design could be improved in the future by enrolling a larger patient population and focusing more on localized delivery rather than intravenous transplantation. Trials should also introduce a more standardized method of analyzing and reporting clinical outcomes to achieve a better comparable outcome and possibly recognize the full potential that these cells have to offer.
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Affiliation(s)
- Noora Hassani
- Regenerative Medicine Centre, Arabian Gulf University, Manama, Bahrain
- Department of Molecular Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain
| | - Sebastien Taurin
- Regenerative Medicine Centre, Arabian Gulf University, Manama, Bahrain
- Department of Molecular Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain
| | - Sfoug Alshammary
- Regenerative Medicine Centre, Arabian Gulf University, Manama, Bahrain
- Department of Molecular Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain
- Correspondence: Sfoug Alshammary Email
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Bu ZQ, Yu HY, Wang J, He X, Cui YR, Feng JC, Feng J. Emerging Role of Ferroptosis in the Pathogenesis of Ischemic Stroke: A New Therapeutic Target? ASN Neuro 2021; 13:17590914211037505. [PMID: 34463559 PMCID: PMC8424725 DOI: 10.1177/17590914211037505] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Ischemic stroke is one of the main causes of high morbidity, mortality, and disability
worldwide; however, the treatment methods are limited and do not always achieve
satisfactory results. The pathogenesis of ischemic stroke is complex, defined by multiple
mechanisms; among them, programmed death of neuronal cells plays a significant role.
Ferroptosis is a novel type of regulated cell death characterized by iron redistribution
or accumulation and increased lipid peroxidation in the membrane. Ferroptosis is
implicated in many pathological conditions, such as cancer, neurodegenerative diseases,
and ischemia-reperfusion injury. In this review, we summarize current research findings on
ferroptosis, including possible molecular mechanisms and therapeutic applications of
ferroptosis regulators, with a focus on the involvement of ferroptosis in the pathogenesis
and treatment of ischemic stroke. Understanding the role of ferroptosis in ischemic stroke
will throw some light on the development of methods for diagnosis, treatment, and
prevention of this devastating disease.
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Affiliation(s)
- Zhong-Qi Bu
- Department of Neurology, 85024Shengjing Hospital of China Medical University, Shenyang, China
| | - Hai-Yang Yu
- Department of Neurology, 85024Shengjing Hospital of China Medical University, Shenyang, China
| | - Jue Wang
- Department of Neurology, 85024Shengjing Hospital of China Medical University, Shenyang, China
| | - Xin He
- Department of Neurology, 85024Shengjing Hospital of China Medical University, Shenyang, China
| | - Yue-Ran Cui
- Department of Neurology, 85024Shengjing Hospital of China Medical University, Shenyang, China
| | - Jia-Chun Feng
- Department of Neurology and Neuroscience Center, 117971The First Hospital of Jilin University, Changchun, China
| | - Juan Feng
- Department of Neurology, 85024Shengjing Hospital of China Medical University, Shenyang, China
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Wang J, Zhao J, Li S. Research progress on the therapeutic effect of olfactory ensheathing cell transplantation on ischemic stroke. JOURNAL OF NEURORESTORATOLOGY 2021. [DOI: 10.26599/jnr.2021.9040012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Olfactory ensheathing cells (OECs) are a special type of glial cell in the olfactory system, which exhibit neuroprotective, immunomodulatory, and angiogenic effects. Although many studies have focused on the reversal of demyelination and axonal degeneration (during spinal cord injury) by OECs, few reports have focused on the ability of OECs to repair ischemic nerve injury. This article reviews the protective effects of OEC transplantation in ischemic stroke and provides a theoretical basis and new strategy for OEC transplantation in the treatment of ischemic stroke.
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Othman FA, Tan SC. Preconditioning Strategies to Enhance Neural Stem Cell-Based Therapy for Ischemic Stroke. Brain Sci 2020; 10:893. [PMID: 33238363 PMCID: PMC7700351 DOI: 10.3390/brainsci10110893] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 11/18/2020] [Indexed: 02/05/2023] Open
Abstract
Transplantation of neural stem cells (NSCs) has been proposed as an alternative novel therapy to replace damaged neural circuitry after ischemic stroke onset. Nonetheless, albeit the potential of these cells for stroke therapy, many critical challenges are yet to be overcome to reach clinical applications. The major limitation of the NSC-based therapy is its inability to retain most of the donor stem cells after grafting into an ischemic brain area which is lacking of essential oxygen and nutrients for the survival of transplanted cells. Low cell survival rate limits the capacity of NSCs to repair the injured area and this poses a much more difficult challenge to the NSC-based therapy for ischemic stroke. In order to enhance the survival of transplanted cells, several stem cell culture preconditioning strategies have been employed. For ischemic diseases, hypoxic preconditioning is the most commonly applied strategy since the last few decades. Now, the preconditioning strategies have been developed and expanded enormously throughout years of efforts. This review systematically presented studies searched from PubMed, ScienceDirect, Web of Science, Scopus and the Google Scholar database up to 31 March 2020 based on search words containing the following terms: "precondition" or "pretreatment" and "neural stem cell" and "ischemic stroke". The searched data comprehensively reported seven major NSC preconditioning strategies including hypoxic condition, small drug molecules such as minocycline, doxycycline, interleukin-6, adjudin, sodium butyrate and nicorandil, as well as electrical stimulation using conductive polymer for ischemic stroke treatment. We discussed therapeutic benefits gained from these preconditioned NSC for in vitro and in vivo stroke studies and the detailed insights of the mechanisms underlying these preconditioning approaches. Nonetheless, we noticed that there was a scarcity of evidence on the efficacy of these preconditioned NSCs in human clinical studies, therefore, it is still too early to draw a definitive conclusion on the efficacy and safety of this active compound for patient usage. Thus, we suggest for more in-depth clinical investigations of this cell-based therapy to develop into more conscientious and judicious evidence-based therapy for clinical application in the future.
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Affiliation(s)
| | - Suat Cheng Tan
- School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia;
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Clinical Trials of Stem Cell Therapy for Cerebral Ischemic Stroke. Int J Mol Sci 2020; 21:ijms21197380. [PMID: 33036265 PMCID: PMC7582939 DOI: 10.3390/ijms21197380] [Citation(s) in RCA: 118] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 09/24/2020] [Accepted: 10/02/2020] [Indexed: 12/17/2022] Open
Abstract
Despite recent developments in innovative treatment strategies, stroke remains one of the leading causes of death and disability worldwide. Stem cell therapy is currently attracting much attention due to its potential for exerting significant therapeutic effects on stroke patients. Various types of cells, including bone marrow mononuclear cells, bone marrow/adipose-derived stem/stromal cells, umbilical cord blood cells, neural stem cells, and olfactory ensheathing cells have enhanced neurological outcomes in animal stroke models. These stem cells have also been tested via clinical trials involving stroke patients. In this article, the authors review potential molecular mechanisms underlying neural recovery associated with stem cell treatment, as well as recent advances in stem cell therapy, with particular reference to clinical trials and future prospects for such therapy in treating stroke.
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Nucci MP, Filgueiras IS, Ferreira JM, de Oliveira FA, Nucci LP, Mamani JB, Rego GNA, Gamarra LF. Stem cell homing, tracking and therapeutic efficiency evaluation for stroke treatment using nanoparticles: A systematic review. World J Stem Cells 2020; 12:381-405. [PMID: 32547686 PMCID: PMC7280869 DOI: 10.4252/wjsc.v12.i5.381] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 04/02/2020] [Accepted: 04/23/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Stroke is the second leading cause of death worldwide. There is a real need to develop treatment strategies for reducing neurological deficits in stroke survivors, and stem cell (SC) therapeutics appear to be a promising alternative for stroke therapy that can be used in combination with approved thrombolytic or thrombectomy approaches. However, the efficacy of SC therapy depends on the SC homing ability and engraftment into the injury site over a long period of time. Nonetheless, tracking SCs from their niche to the target tissues is a complex process.
AIM To evaluate SC migration homing, tracking and therapeutic efficacy in the treatment of stroke using nanoparticles
METHODS A systematic literature search was performed to identify articles published prior to November 2019 that were indexed in PubMed and Scopus. The following inclusion criteria were used: (1) Studies that used in vivo models of stroke or ischemic brain lesions; (2) Studies of SCs labeled with some type of contrast agent for cell migration detection; and (3) Studies that involved in vivo cellular homing and tracking analysis.
RESULTS A total of 82 articles were identified by indexing in Scopus and PubMed. After the inclusion criteria were applied, 35 studies were selected, and the articles were assessed for eligibility; ultimately, only 25 studies were included. Most of the selected studies used SCs from human and mouse bone marrow labeled with magnetic nanoparticles alone or combined with fluorophore dyes. These cells were administered in the stroke model (to treat middle cerebral artery occlusion in 74% of studies and for photothrombotic induction in 26% of studies). Fifty-three percent of studies used xenogeneic grafts for cell therapy, and the migration homing and tracking evaluation was performed by magnetic resonance imaging as well as other techniques, such as near-infrared fluorescence imaging (12%) or bioluminescence assays (12%).
CONCLUSION Our systematic review provided an up-to-date evaluation of SC migration homing and the efficacy of cellular therapy for stroke treatment in terms of functional and structural improvements in the late stage.
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Affiliation(s)
- Mariana Penteado Nucci
- LIM44, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05529-060, Brazil
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