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1
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Zhang Y, Gu J, Wang X, Li L, Fu L, Wang D, Wang X, Han X. Opportunities and challenges: mesenchymal stem cells in the treatment of multiple sclerosis. Int J Neurosci 2023; 133:1031-1044. [PMID: 35579409 DOI: 10.1080/00207454.2022.2042690] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 01/08/2022] [Accepted: 02/09/2022] [Indexed: 10/18/2022]
Abstract
Multiple sclerosis (MS) was once considered an untreatable disease. Through years of research, many drugs have been discovered and are widely used for the treatment of MS. However, the current treatment can only alleviate the clinical symptoms of MS and has serious side effects. Mesenchymal stem cells (MSCs) provide neuroprotection by migrating to injured tissues, suppressing inflammation, and fostering neuronal repair. Therefore, MSCs therapy holds great promise for MS treatment. This review aimed to assess the feasibility and safety of use of MSCs in MS treatment as well as its development prospect in clinical treatment by analysing the existing clinical studies.
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Affiliation(s)
- Yingyu Zhang
- Department of Neurology, China-Japan Union hospital of Jilin University, Changchun city, Jilin, P.R. China
| | - Jiebing Gu
- Department of Neurology, China-Japan Union hospital of Jilin University, Changchun city, Jilin, P.R. China
| | - Xiaoshuang Wang
- Department of Neurology, China-Japan Union hospital of Jilin University, Changchun city, Jilin, P.R. China
| | - Linfang Li
- Department of Neurology, China-Japan Union hospital of Jilin University, Changchun city, Jilin, P.R. China
| | - Lingling Fu
- Department of Neurology, China-Japan Union hospital of Jilin University, Changchun city, Jilin, P.R. China
| | - Di Wang
- Department of Neurology, China-Japan Union hospital of Jilin University, Changchun city, Jilin, P.R. China
| | - Xiuting Wang
- Department of Neurology, China-Japan Union hospital of Jilin University, Changchun city, Jilin, P.R. China
| | - Xuemei Han
- Department of Neurology, China-Japan Union hospital of Jilin University, Changchun city, Jilin, P.R. China
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2
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Zhou L, Wang J, Huang J, Song X, Wu Y, Chen X, Tan Y, Yang Q. The role of mesenchymal stem cell transplantation for ischemic stroke and recent research developments. Front Neurol 2022; 13:1000777. [PMID: 36468067 PMCID: PMC9708730 DOI: 10.3389/fneur.2022.1000777] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 10/03/2022] [Indexed: 09/08/2023] Open
Abstract
Ischemic stroke is a common cerebrovascular disease that seriously affects human health. However, most patients do not practice self-care and cannot rely on the current clinical treatment for guaranteed functional recovery. Stem cell transplantation is an emerging treatment studied in various central nervous system diseases. More importantly, animal studies show that transplantation of mesenchymal stem cells (MSCs) can alleviate neurological deficits and bring hope to patients suffering from ischemic stroke. This paper reviews the biological characteristics of MSCs and discusses the mechanism and progression of MSC transplantation to provide new therapeutic directions for ischemic stroke.
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Affiliation(s)
| | | | | | | | | | | | | | - Qin Yang
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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3
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Zhu D, Fang H, Yu H, Liu P, Yang Q, Luo P, Zhang C, Gao Y, Chen YX. Alcohol-induced inhibition of bone formation and neovascularization contributes to the failure of fracture healing via the miR-19a-3p/FOXF2 axis. Bone Joint Res 2022; 11:386-397. [PMID: 35730670 PMCID: PMC9233406 DOI: 10.1302/2046-3758.116.bjr-2021-0596.r1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Aims Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood. Methods MicroRNA (miR) sequencing was performed on bone mesenchymal stem cells (BMSCs). The effects of alcohol and miR-19a-3p on vascularization and osteogenic differentiation were analyzed in vitro using BMSCs and human umbilical vein endothelial cells (HUVECs). An in vivo alcohol-fed mouse model of femur fracture healing was also established, and radiological and histomorphometric analyses were used to evaluate the role of miR-19a-3p. The binding of miR-19a-3p to forkhead box F2 (FOXF2) was analyzed using a luciferase reporter assay. Results miR-19a-3p was identified as one of the key regulators in the osteogenic differentiation of BMSCs, and was found to be downregulated in the alcohol-fed mouse model of fracture healing. In vitro, miR-19a-3p expression was downregulated after ethanol administration in both BMSCs and HUVECs. Vascularization and osteogenic differentiation were independently suppressed by ethanol and reversed by miR-19a-3p. In addition, the luciferase reporter assay showed that FOXF2 is the direct binding target of miR-19a-3p. In vivo, miR-19a-3p agomir stimulated callus transformation and improved the alcohol-impaired fracture healing. Conclusion This study is the first to demonstrate that the miR-19a-3p/FOXF2 axis has a pivotal role in alcohol-impaired fracture healing, and may be a potential therapeutic target. Cite this article: Bone Joint Res 2022;11(6):386–397.
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Affiliation(s)
- Daoyu Zhu
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Haoyu Fang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Hongping Yu
- Department of Orthopedic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Pei Liu
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Qianhao Yang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Pengbo Luo
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Changqing Zhang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.,Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Youshui Gao
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Yi-Xuan Chen
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
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4
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Liu Y, Zhao Y, Min Y, Guo K, Chen Y, Huang Z, Long C. Effects and Mechanisms of Bone Marrow Mesenchymal Stem Cell Transplantation for Treatment of Ischemic Stroke in Hypertensive Rats. Int J Stem Cells 2021; 15:217-226. [PMID: 34966000 PMCID: PMC9148836 DOI: 10.15283/ijsc21136] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 09/13/2021] [Accepted: 09/24/2021] [Indexed: 11/09/2022] Open
Abstract
Background and Objectives Stroke is the most common cause of human death and functional disability, resulting in more than 5 million deaths worldwide each year. Bone marrow mesenchymal stem cells (BMSCs) are a kind of stem cell that are able to self-renew and differentiate into many types of tissues. Therefore, BMSCs have the potential to replace damaged neurons and promote the reconstruction of nerve conduction pathways and connective tissue. However, it remains unknown whether transplanted BMSCs promote angiogenesis or improve the tissue microenvironment directly or indirectly through paracrine interactions. This study aimed to determine the therapeutic effect of BMSCs on ischemic stroke with hypertension in a rodent model and to explore the possible mechanisms underlying any benefits. Methods and Results Middle cerebral artery occlusion was used to establish the experimental stroke model. The area of cerebral infarction, expression of vascular endothelial growth factor (VEGF) and glial cell line-derived neurotrophic factor (GDNF), and increment of astrocyte were measured by TTC staining, western blot, real-time quantitative polymerase chain reaction (RT-qPCR) and immunocytochemistry. The results showed a smaller area of cerebral infarction and improved neurological function scores in animals treated with BMSCs compared to controls. The results of RT-qPCR and western blot assays showed higher expression of VEGF and GDNF in BMSC-treated animals compared with controls. Our study also showed that one round of BMSCs transplantation significantly promoted the proliferation of subventricular zone and cortical cells, especially astrocytes, on the ischemic side following cerebral ischemia. Conclusions Above findings support that BMSCs have therapeutic effects for ischemic stroke complicated with hypertension, which may occur via up-regulated expression of VEGF and GDNF and reduction of neuronal apoptosis, thereby promoting the recovery of nerve function.
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Affiliation(s)
- Yulin Liu
- Department of Rehabilitation Medicine, Panyu Central Hospital, Guangzhou, China
| | - Ying Zhao
- South China Normal University-Panyu Central Hospital Joint Laboratory of Translational Medical Research, Panyu Central Hospital, Guangzhou, China.,School of Life Sciences, South China Normal University, Guangzhou, China
| | - Yu Min
- Department of Rehabilitation Medicine, Panyu Central Hospital, Guangzhou, China
| | - Kaifeng Guo
- Department of Rehabilitation Medicine, Panyu Central Hospital, Guangzhou, China
| | - Yuling Chen
- Department of Rehabilitation Medicine, Panyu Central Hospital, Guangzhou, China
| | - Zhen Huang
- Department of Rehabilitation Medicine, Panyu Central Hospital, Guangzhou, China
| | - Cheng Long
- South China Normal University-Panyu Central Hospital Joint Laboratory of Translational Medical Research, Panyu Central Hospital, Guangzhou, China.,School of Life Sciences, South China Normal University, Guangzhou, China
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5
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Xin WQ, Wei W, Pan YL, Cui BL, Yang XY, Bähr M, Doeppner TR. Modulating poststroke inflammatory mechanisms: Novel aspects of mesenchymal stem cells, extracellular vesicles and microglia. World J Stem Cells 2021; 13:1030-1048. [PMID: 34567423 PMCID: PMC8422926 DOI: 10.4252/wjsc.v13.i8.1030] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/25/2021] [Accepted: 08/06/2021] [Indexed: 02/06/2023] Open
Abstract
Inflammation plays an important role in the pathological process of ischemic stroke, and systemic inflammation affects patient prognosis. As resident immune cells in the brain, microglia are significantly involved in immune defense and tissue repair under various pathological conditions, including cerebral ischemia. Although the differentiation of M1 and M2 microglia is certainly oversimplified, changing the activation state of microglia appears to be an intriguing therapeutic strategy for cerebral ischemia. Recent evidence indicates that both mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) regulate inflammation and modify tissue repair under preclinical stroke conditions. However, the precise mechanisms of these signaling pathways, especially in the context of the mutual interaction between MSCs or MSC-derived EVs and resident microglia, have not been sufficiently unveiled. Hence, this review summarizes the state-of-the-art knowledge on MSC- and MSC-EV-mediated regulation of microglial activity under ischemic stroke conditions with respect to various signaling pathways, including cytokines, neurotrophic factors, transcription factors, and microRNAs.
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Affiliation(s)
- Wen-Qiang Xin
- Department of Neurology, University Medical Center Göttingen, Göttingen 37075, Germany
| | - Wei Wei
- Department of Neurology, University Medical Center Göttingen, Göttingen 37075, Germany
| | - Yong-Li Pan
- Department of Neurology, University Medical Center Göttingen, Göttingen 37075, Germany
| | - Bao-Long Cui
- Department of Neurology, University Medical Center Göttingen, Göttingen 37075, Germany
| | - Xin-Yu Yang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Mathias Bähr
- Department of Neurology, University Medical Center Göttingen, Göttingen 37075, Germany
| | - Thorsten R Doeppner
- Department of Neurology, University Medical Center Göttingen, Göttingen 37075, Germany
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6
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Tian C, Yang Y, Bai B, Wang S, Liu M, Sun RC, Yu T, Chu XM. Potential of exosomes as diagnostic biomarkers and therapeutic carriers for doxorubicin-induced cardiotoxicity. Int J Biol Sci 2021; 17:1328-1338. [PMID: 33867849 PMCID: PMC8040474 DOI: 10.7150/ijbs.58786] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 03/17/2021] [Indexed: 02/07/2023] Open
Abstract
Doxorubicin (DOX) is a kind of representative anthracyclines. It has greatly prolonged lifespan of cancer patients. However, a long course of DOX chemotherapy could induce various forms of deaths of cardiomyocytes, such as apoptosis, pyroptosis and ferroptosis, contributing to varieties of cardiac complications called cardiotoxicity. It has become a major concern considering the large number of cancer patients' worldwide and increased survival rates after chemotherapy. Exosomes, a subgroup of extracellular vesicles (EVs), are secreted by nearly all cells and consist of lipid bilayers, nucleic acids and proteins. They can serve as mediators between intercellular communication via the transfer of bioactive molecules from secretory to recipient cells, modulating multiple pathophysiological processes. It has been proven that exosomes in body fluids can serve as biomarkers for doxorubicin-induced cardiotoxicity (DIC). Moreover, exosomes have attracted considerable attention because of their capacity as carriers of certain proteins, genetic materials (miRNA and lncRNA), and chemotherapeutic drugs to decrease the dosage of DOX and alleviate cardiotoxicity. This review briefly describes the characteristics of exosomes and highlights their clinical application potential as diagnostic biomarkers and drug delivery vehicles for DIC, thus providing a strategy for addressing it based on exosomes.
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Affiliation(s)
- Chao Tian
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China
| | - Yanyan Yang
- Department of Immunology, Basic Medicine School, Qingdao University, Qingdao 266071, China
| | - Baochen Bai
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China
| | - Shizhong Wang
- Department of Cardiovascular Surgery, The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao 266000, China
| | - Meixin Liu
- Department of Cardiac Ultrasound, The Affiliated hospital of Qingdao University, Qingdao 266000, China
| | - Rui-Cong Sun
- Department of Cardiac Ultrasound, The Affiliated hospital of Qingdao University, Qingdao 266000, China
| | - Tao Yu
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266021, China
- Department of Cardiac Ultrasound, The Affiliated hospital of Qingdao University, Qingdao 266000, China
| | - Xian-ming Chu
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China
- Department of Cardiology, The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao 266032, China
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7
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Rajendran RL, Jogalekar MP, Gangadaran P, Ahn BC. Noninvasive in vivo cell tracking using molecular imaging: A useful tool for developing mesenchymal stem cell-based cancer treatment. World J Stem Cells 2020; 12:1492-1510. [PMID: 33505597 PMCID: PMC7789123 DOI: 10.4252/wjsc.v12.i12.1492] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 10/05/2020] [Accepted: 10/21/2020] [Indexed: 02/06/2023] Open
Abstract
Mounting evidence has emphasized the potential of cell therapies in treating various diseases by restoring damaged tissues or replacing defective cells in the body. Cell therapies have become a strong therapeutic modality by applying noninvasive in vivo molecular imaging for examining complex cellular processes, understanding pathophysiological mechanisms of diseases, and evaluating the kinetics/dynamics of cell therapies. In particular, mesenchymal stem cells (MSCs) have shown promise in recent years as drug carriers for cancer treatment. They can also be labeled with different probes and tracked in vivo to assess the in vivo effect of administered cells, and to optimize therapy. The exact role of MSCs in oncologic diseases is not clear as MSCs have been shown to be involved in tumor progression and inhibition, and the exact interactions between MSCs and specific cancer microenvironments are not clear. In this review, a multitude of labeling approaches, imaging modalities, and the merits/demerits of each strategy are outlined. In addition, specific examples of the use of MSCs and in vivo imaging in cancer therapy are provided. Finally, present limitations and future outlooks in terms of the translation of different imaging approaches in clinics are discussed.
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Affiliation(s)
| | | | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
| | - Byeong-Cheol Ahn
- BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, South Korea.
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8
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Li L, Chu L, Ren C, Wang J, Sun S, Li T, Yin Y. Enhanced Migration of Bone Marrow-Derived Mesenchymal Stem Cells with Tetramethylpyrazine and Its Synergistic Effect on Angiogenesis and Neurogenesis After Cerebral Ischemia in Rats. Stem Cells Dev 2019; 28:871-881. [PMID: 31038013 DOI: 10.1089/scd.2018.0254] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Bone marrow-derived mesenchymal stem cells (BMSCs) hold great promise for treating ischemic stroke owing to their capacity to secrete various trophic factors with potent angiogenic and neurogenic potentials. However, the relatively poor migratory capacity of BMSCs toward infarcted regions limits effective therapies for the treatment of stroke. The combination of BMSCs and pharmacological agent can promote the migration of BMSCs toward infarcted regions and improve the therapeutic effects after stroke. In this study, we aimed to investigate whether BMSCs combined with tetramethylpyrazine (TMP) enhanced BMSC migration into the ischemic brain, which had better therapeutic effect in the treatment of stroke. In a rat stroke model, we found that combination treatment significantly upregulated ischemic brain stromal-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) expressions, and promoted BMSCs homing toward the ischemic regions than BMSC monotherapy. Moreover, BMSCs combined with TMP synergistically increased the expression of vascular endothelial growth factor and brain-derived neurotrophic factor, promoted angiogenesis and neurogenesis, and improved functional outcome after stroke. These results suggest that combination treatment could not only enhance the migration of BMSCs into the ischemic brain but also act in a synergistic way to potentiate endogenous repair processes and functional recovery after ischemic stroke.
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Affiliation(s)
- Lin Li
- Department of Physiology, Zhejiang Chinese Medical University, Zhejiang, China
| | - Lisheng Chu
- Department of Physiology, Zhejiang Chinese Medical University, Zhejiang, China
| | - Cuicui Ren
- Department of Physiology, Zhejiang Chinese Medical University, Zhejiang, China
| | - Jun Wang
- Department of Physiology, Zhejiang Chinese Medical University, Zhejiang, China
| | - Siqi Sun
- Department of Physiology, Zhejiang Chinese Medical University, Zhejiang, China
| | - Tianyi Li
- Department of Physiology, Zhejiang Chinese Medical University, Zhejiang, China
| | - Yuanjun Yin
- Department of Physiology, Zhejiang Chinese Medical University, Zhejiang, China
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9
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Abstract
Central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI) and spinal cord injury (SCI), are important causes of death and long-term disability worldwide. MicroRNA (miRNA), small non-coding RNA molecules that negatively regulate gene expression, can serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. MiRNA-based therapeutics include miRNA mimics and inhibitors (antagomiRs) to respectively decrease and increase the expression of target genes. In this review, we summarize current miRNA-based therapeutic applications in stroke, TBI and SCI. Administration methods, time windows and dosage for effective delivery of miRNA-based drugs into CNS are discussed. The underlying mechanisms of miRNA-based therapeutics are reviewed including oxidative stress, inflammation, apoptosis, blood-brain barrier protection, angiogenesis and neurogenesis. Pharmacological agents that protect against CNS injuries by targeting specific miRNAs are presented along with the challenges and therapeutic potential of miRNA-based therapies.
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Affiliation(s)
- Ping Sun
- Department of Neurology, Pittsburgh Institute of Brain Disorders & Recovery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Da Zhi Liu
- Department of Neurology and the M.I.N.D. Institute, University of California at Davis, Sacramento, CA, USA
| | - Glen C Jickling
- Department of Neurology, University of Alberta, Edmonton, Alberta, Canada
| | - Frank R Sharp
- Department of Neurology and the M.I.N.D. Institute, University of California at Davis, Sacramento, CA, USA
| | - Ke-Jie Yin
- Department of Neurology, Pittsburgh Institute of Brain Disorders & Recovery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- Ke-Jie Yin, Department of Neurology, Pittsburgh Institute of Brain Disorders & Recovery, University of Pittsburgh School of Medicine, 200 Lothrop Street, BST S514, Pittsburgh, PA 15213, USA. Da Zhi Liu, Department of Neurology, University of California at Davis, Sacramento, CA 95817, USA.
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10
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Regulation of proliferation and functioning of transplanted cells by using herpes simplex virus thymidine kinase gene in mice. J Control Release 2018; 275:78-84. [DOI: 10.1016/j.jconrel.2018.02.018] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Revised: 01/26/2018] [Accepted: 02/13/2018] [Indexed: 01/01/2023]
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11
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González-Nieto D, Fernández-García L, Pérez-Rigueiro J, Guinea GV, Panetsos F. Hydrogels-Assisted Cell Engraftment for Repairing the Stroke-Damaged Brain: Chimera or Reality. Polymers (Basel) 2018; 10:polym10020184. [PMID: 30966220 PMCID: PMC6415003 DOI: 10.3390/polym10020184] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Revised: 02/06/2018] [Accepted: 02/11/2018] [Indexed: 01/07/2023] Open
Abstract
The use of advanced biomaterials as a structural and functional support for stem cells-based therapeutic implants has boosted the development of tissue engineering applications in multiple clinical fields. In relation to neurological disorders, we are still far from the clinical reality of restoring normal brain function in neurodegenerative diseases and cerebrovascular disorders. Hydrogel polymers show unique mechanical stiffness properties in the range of living soft tissues such as nervous tissue. Furthermore, the use of these polymers drastically enhances the engraftment of stem cells as well as their capacity to produce and deliver neuroprotective and neuroregenerative factors in the host tissue. Along this article, we review past and current trends in experimental and translational research to understand the opportunities, benefits, and types of tentative hydrogel-based applications for the treatment of cerebral disorders. Although the use of hydrogels for brain disorders has been restricted to the experimental area, the current level of knowledge anticipates an intense development of this field to reach clinics in forthcoming years.
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Affiliation(s)
- Daniel González-Nieto
- Center for Biomedical Technology, Universidad Politécnica de Madrid, 28040 Madrid, Spain.
- Departamento de Tecnología Fotónica y Bioingeniería, ETSI Telecomunicaciones, Universidad Politécnica de Madrid, 28040 Madrid, Spain.
- Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine (CIBER-BBN), 28040 Madrid, Spain.
| | - Laura Fernández-García
- Center for Biomedical Technology, Universidad Politécnica de Madrid, 28040 Madrid, Spain.
| | - José Pérez-Rigueiro
- Center for Biomedical Technology, Universidad Politécnica de Madrid, 28040 Madrid, Spain.
- Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine (CIBER-BBN), 28040 Madrid, Spain.
- Departamento de Ciencia de Materiales, ETSI Caminos, Canales y Puertos, Universidad Politécnica de Madrid 28040 Madrid, Spain.
| | - Gustavo V Guinea
- Center for Biomedical Technology, Universidad Politécnica de Madrid, 28040 Madrid, Spain.
- Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine (CIBER-BBN), 28040 Madrid, Spain.
- Departamento de Ciencia de Materiales, ETSI Caminos, Canales y Puertos, Universidad Politécnica de Madrid 28040 Madrid, Spain.
| | - Fivos Panetsos
- Neurocomputing and Neurorobotics Research Group: Faculty of Biology and Faculty of Optics, Universidad Complutense de Madrid, 28040 Madrid, Spain.
- Instituto de Investigación Sanitaria, Hospital Clínico San Carlos Madrid, IdISSC, 28040 Madrid, Spain.
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12
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Chen H, Huang Y, Huang D, Wu Z, Li Y, Zhou C, Wei G. Protective effect of gigantol against hydrogen peroxide‑induced apoptosis in rat bone marrow mesenchymal stem cells through the PI3K/Akt pathway. Mol Med Rep 2017; 17:3267-3273. [PMID: 29257286 DOI: 10.3892/mmr.2017.8242] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Accepted: 10/24/2017] [Indexed: 11/05/2022] Open
Abstract
Bone marrow mesenchymal stem cell (BMSC) transplants are promising for the treatment of certain central nervous system diseases. However, oxidative stress is one of the major factors that may limit the survival of the transplanted BMSCs. The present study investigated the effect of pretreatment with gigantol on hydrogen peroxide (H2O2)‑induced apoptosis in rat BMSCs (rBMSCs) and the potential underlying mechanisms. The results demonstrated that gigantol pretreatment significantly inhibited H2O2‑induced apoptosis of rBMSCs. rBMSCs were incubated with 600 µM H2O2 in the absence or presence of different doses of gigantol (1‑100 µM). Cell viability and apoptosis ratios were assessed by MTT assays and flow cytometry, respectively. Morphological alterations and reactive oxygen species were measured by the fluorescent‑based methods of Hoechst staining and dichlorodihydrofluorescein diacetate, respectively. Furthermore, the protein levels of phosphorylated‑protein kinase B (Akt), B‑cell lymphoma‑2 (Bcl‑2), Bcl‑2‑associated X (Bax), caspase‑3 and caspase‑9 were investigated by western blotting. Following incubation with H2O2 for 2 h, gigantol significantly inhibited the H2O2‑induced reductions in the cell viability of rBMSCs in a dose‑dependent manner. Furthermore, gigantol upregulated Akt phosphorylation and Bcl‑2 expression, downregulated Bax expression, and reduced the expression of caspase‑3 and caspase‑9 in H2O2‑treated rBMSCs, whereas an opposite effect was detected when LY294002, an inhibitor of phosphatidylinositol 3‑kinase, was administered in combination with gigantol. These results indicate that gigantol may be developed as a promising neuroprotective agent for successful MSC transplantation in ischemic diseases.
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Affiliation(s)
- Huanhuan Chen
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
| | - Yuechun Huang
- Department of Pharmacy, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Dandan Huang
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
| | - Zhifang Wu
- Department of Trauma Orthopedics, The Third Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510360, P.R. China
| | - Yunrong Li
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
| | - Chunhua Zhou
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
| | - Gang Wei
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
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13
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14
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Cell-based therapy for acute organ injury: preclinical evidence and ongoing clinical trials using mesenchymal stem cells. Anesthesiology 2014; 121:1099-121. [PMID: 25211170 DOI: 10.1097/aln.0000000000000446] [Citation(s) in RCA: 105] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Critically ill patients often suffer from multiple organ failures involving lung, kidney, liver, or brain. Genomic, proteomic, and metabolomic approaches highlight common injury mechanisms leading to acute organ failure. This underlines the need to focus on therapeutic strategies affecting multiple injury pathways. The use of adult stem cells such as mesenchymal stem or stromal cells (MSC) may represent a promising new therapeutic approach as increasing evidence shows that MSC can exert protective effects following injury through the release of promitotic, antiapoptotic, antiinflammatory, and immunomodulatory soluble factors. Furthermore, they can mitigate metabolomic and oxidative stress imbalance. In this work, the authors review the biological capabilities of MSC and the results of clinical trials using MSC as therapy in acute organ injuries. Although preliminary results are encouraging, more studies concerning safety and efficacy of MSC therapy are needed to determine their optimal clinical use. (ANESTHESIOLOGY 2014; 121:1099-121).
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Wahl AS, Schwab ME. Finding an optimal rehabilitation paradigm after stroke: enhancing fiber growth and training of the brain at the right moment. Front Hum Neurosci 2014; 8:381. [PMID: 25018717 PMCID: PMC4072965 DOI: 10.3389/fnhum.2014.00381] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2013] [Accepted: 05/14/2014] [Indexed: 12/11/2022] Open
Abstract
After stroke the central nervous system reveals a spectrum of intrinsic capacities to react as a highly dynamic system which can change the properties of its circuits, form new contacts, erase others, and remap related cortical and spinal cord regions. This plasticity can lead to a surprising degree of spontaneous recovery. It includes the activation of neuronal molecular mechanisms of growth and of extrinsic growth promoting factors and guidance signals in the tissue. Rehabilitative training and pharmacological interventions may modify and boost these neuronal processes, but almost nothing is known on the optimal timing of the different processes and therapeutic interventions and on their detailed interactions. Finding optimal rehabilitation paradigms requires an optimal orchestration of the internal processes of re-organization and the therapeutic interventions in accordance with defined plastic time windows. In this review we summarize the mechanisms of spontaneous plasticity after stroke and experimental interventions to enhance growth and plasticity, with an emphasis on anti-Nogo-A immunotherapy. We highlight critical time windows of growth and of rehabilitative training and consider different approaches of combinatorial rehabilitative schedules. Finally, we discuss potential future strategies for designing repair and rehabilitation paradigms by introducing a “3 step model”: determination of the metabolic and plastic status of the brain, pharmacological enhancement of its plastic mechanisms, and stabilization of newly formed functional connections by rehabilitative training.
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Affiliation(s)
- Anna-Sophia Wahl
- Brain Research Institute, University of Zurich Zurich, Switzerland ; Department of Health, Sciences and Technology, ETH Zurich Zurich, Switzerland
| | - Martin E Schwab
- Brain Research Institute, University of Zurich Zurich, Switzerland ; Department of Health, Sciences and Technology, ETH Zurich Zurich, Switzerland
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Multipotent neural crest stem cell-like cells from rat vibrissa dermal papilla induce neuronal differentiation of PC12 cells. BIOMED RESEARCH INTERNATIONAL 2014; 2014:186239. [PMID: 25045659 PMCID: PMC4086521 DOI: 10.1155/2014/186239] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Accepted: 04/24/2014] [Indexed: 12/17/2022]
Abstract
Bone marrow mesenchymal stem cells (BMSCs) transplants have been approved for treating central nervous system (CNS) injuries and diseases; however, their clinical applications are limited. Here, we model the therapeutic potential of dermal papilla cells (DPCs) in vitro. DPCs were isolated from rat vibrissae and characterized by immunocytofluorescence, RT-PCR, and multidifferentiation assays. We examined whether these cells could secrete neurotrophic factors (NTFs) by using cocultures of rat pheochromocytoma cells (PC12) with conditioned medium and ELISA assay. DPCs expressed Sox10, P75, Nestin, Sox9, and differentiated into adipocytes, osteoblasts, smooth muscle cells, and neurons under specific inducing conditions. The DPC-conditioned medium (DPC-CM) induced neuronal differentiation of PC12 cells and promoted neurite outgrowth. Results of ELISA assay showed that compared to BMSCs, DPCs secreted more brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Moreover, we observed that, compared with the total DPC population, sphere-forming DPCs expressed higher levels of Nestin and P75 and secreted greater amounts of GDNF. The DPCs from craniofacial hair follicle papilla may be a new and promising source for treating CNS injuries and diseases.
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Hart ML, Neumayer KMH, Vaegler M, Daum L, Amend B, Sievert KD, Di Giovanni S, Kraushaar U, Guenther E, Stenzl A, Aicher WK. Cell-based therapy for the deficient urinary sphincter. Curr Urol Rep 2014; 14:476-87. [PMID: 23824516 DOI: 10.1007/s11934-013-0352-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
When sterile culture techniques of mammalian cells first became state of the art, there was tremendous anticipation that such cells could be eventually applied for therapeutic purposes. The discovery of adult human stem or progenitor cells further motivated scientists to pursue research in cell-based therapies. Although evidence from animal studies suggests that application of cells yields measurable benefits, in urology and many other disciplines, progenitor-cell-based therapies are not yet routinely clinically available. Stress urinary incontinence (SUI) is a condition affecting a large number of patients. The etiology of SUI includes, but is not limited to, degeneration of the urinary sphincter muscle tissue and loss of innervation, as well as anatomical and biomechanical causes. Therefore, different regimens were developed to treat SUI. However, at present, a curative functional treatment is not at hand. A progenitor-cell-based therapy that can tackle the etiology of incontinence, rather than the consequences, is a promising strategy. Therefore, several research teams have intensified their efforts to develop such a therapy for incontinence. Here, we introduce candidate stem and progenitor cells suitable for SUI treatment, show how the functional homogeneity and state of maturity of differentiated cells crucial for proper tissue integration can be assessed electrophysiologically prior to their clinical application, and discuss the trophic potential of adult mesenchymal stromal (or stem) cells in regeneration of neuronal function.
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Affiliation(s)
- Melanie L Hart
- KFO273, Department of Urology, UKT, University of Tuebingen, Paul-Ehrlich-Str. 15, 72076, Tuebingen, Germany
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Wang L, Lin Z, Shao B, Zhuge Q, Jin K. Therapeutic applications of bone marrow-derived stem cells in ischemic stroke. Neurol Res 2013; 35:470-8. [PMID: 23595085 DOI: 10.1179/1743132813y.0000000210] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Liuqing Wang
- Department of Neurology the First Affiliated Hospital, Wenzhou Medical College, China
| | - Zhenzhen Lin
- Department of Neurology the First Affiliated Hospital, Wenzhou Medical College, China
| | - Bei Shao
- Department of Neurology the First Affiliated Hospital, Wenzhou Medical College, China
| | - Qichuan Zhuge
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Researchthe First Affiliated Hospital, Wenzhou Medical College, China
| | - Kunlin Jin
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Researchthe First Affiliated Hospital, Wenzhou Medical College, China
- Department of Pharmacology and NeuroscienceInstitute for Aging and Alzheimer’s Disease Research, University of North Texas Health Science Center at Fort Worth, USA
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Mesenchymal stem cells: angels or demons? J Biomed Biotechnol 2011; 2011:459510. [PMID: 21822372 PMCID: PMC3142786 DOI: 10.1155/2011/459510] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2011] [Revised: 06/01/2011] [Accepted: 06/01/2011] [Indexed: 02/08/2023] Open
Abstract
Mesenchymal stem cells (MSCs) have been used in cell-based therapy in various disease conditions such as graft-versus-host and heart diseases, osteogenesis imperfecta, and spinal cord injuries, and the results have been encouraging. However, as MSC therapy gains popularity among practitioners and researchers, there have been reports on the adverse effects of MSCs especially in the context of tumour modulation and malignant transformation. These cells have been found to enhance tumour growth and metastasis in some studies and have been related to anticancer-drug resistance in other instances. In addition, various studies have also reported spontaneous malignant transformation of MSCs. The mechanism of the modulatory behaviour and the tumorigenic potential of MSCs, warrant urgent exploration, and the use of MSCs in patients with cancer awaits further evaluation. However, if MSCs truly play a role in tumour modulation, they can also be potential targets of cancer treatment.
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Jang S, Cho HH, Cho YB, Park JS, Jeong HS. Functional neural differentiation of human adipose tissue-derived stem cells using bFGF and forskolin. BMC Cell Biol 2010; 11:25. [PMID: 20398362 PMCID: PMC2867791 DOI: 10.1186/1471-2121-11-25] [Citation(s) in RCA: 204] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2009] [Accepted: 04/16/2010] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Adult mesenchymal stem cells (MSCs) derived from adipose tissue have the capacity to differentiate into mesenchymal as well as endodermal and ectodermal cell lineage in vitro. We characterized the multipotent ability of human adipose tissue-derived stem cells (hADSCs) as MSCs and investigated the neural differentiation potential of these cells. RESULTS Human ADSCs from earlobe fat maintained self-renewing capacity and differentiated into adipocytes, osteoblasts, or chondrocytes under specific culture conditions. Following neural induction with bFGF and forskolin, hADSCs were differentiated into various types of neural cells including neurons and glia in vitro. In neural differentiated-hADSCs (NI-hADSCs), the immunoreactivities for neural stem cell marker (nestin), neuronal markers (Tuj1, MAP2, NFL, NFM, NFH, NSE, and NeuN), astrocyte marker (GFAP), and oligodendrocyte marker (CNPase) were significantly increased than in the primary hADSCs. RT-PCR analysis demonstrated that the mRNA levels encoding for ABCG2, nestin, Tuj1, MAP2, NFL, NFM, NSE, GAP43, SNAP25, GFAP, and CNPase were also highly increased in NI-hADSCs. Moreover, NI-hADSCs acquired neuron-like functions characterized by the display of voltage-dependent tetrodotoxin (TTX)-sensitive sodium currents, outward potassium currents, and prominent negative resting membrane potentials under whole-cell patch clamp recordings. Further examination by RT-PCR showed that NI-hADSCs expressed high level of ionic channel genes for sodium (SCN5A), potassium (MaxiK, Kv4.2, and EAG2), and calcium channels (CACNA1C and CACNA1G), which were expressed constitutively in the primary hADSCs. In addition, we demonstrated that Kv4.3 and Eag1, potassium channel genes, and NE-Na, a TTX-sensitive sodium channel gene, were highly induced following neural differentiation. CONCLUSIONS These combined results indicate that hADSCs have the same self-renewing capacity and multipotency as stem cells, and can be differentiated into functional neurons using bFGF and forskolin.
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Affiliation(s)
- Sujeong Jang
- Department of Physiology, Chonnam National University Medical School, Gwangju 501190, Republic of Korea
- Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, 501-190, Republic of Korea
- Research Institute of Medical Sciences, Chonnam National University, Gwangju 501-190, Republic of Korea
| | - Hyong-Ho Cho
- Department of Otolaryngology, Chonnam National University Medical School, Gwangju 501190, Republic of Korea
- Research Institute of Medical Sciences, Chonnam National University, Gwangju 501-190, Republic of Korea
| | - Yong-Bum Cho
- Department of Otolaryngology, Chonnam National University Medical School, Gwangju 501190, Republic of Korea
- Research Institute of Medical Sciences, Chonnam National University, Gwangju 501-190, Republic of Korea
| | - Jong-Seong Park
- Department of Physiology, Chonnam National University Medical School, Gwangju 501190, Republic of Korea
- Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, 501-190, Republic of Korea
- Research Institute of Medical Sciences, Chonnam National University, Gwangju 501-190, Republic of Korea
| | - Han-Seong Jeong
- Department of Physiology, Chonnam National University Medical School, Gwangju 501190, Republic of Korea
- Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, 501-190, Republic of Korea
- Research Institute of Medical Sciences, Chonnam National University, Gwangju 501-190, Republic of Korea
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You MH, Kim WJ, Shim W, Lee SR, Lee G, Choi S, Kim DY, Kim YM, Kim H, Han SU. Cytosine deaminase-producing human mesenchymal stem cells mediate an antitumor effect in a mouse xenograft model. J Gastroenterol Hepatol 2009; 24:1393-400. [PMID: 19486256 DOI: 10.1111/j.1440-1746.2009.05862.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Stem cell transplantation offers potential gene therapy for brain tumors. However, this approach has received little attention as a treatment for gastrointestinal tumors. In the present study, we explored the possibility of human bone marrow-derived mesenchymal stem cells (hMSC) producing cytosine deaminase (CD), followed by systemic 5-fluorocytosine (5-FC) administration, showing an antitumor effect on a mouse gastric cancer xenograft. METHODS We first explored the ability of hMSC, coated with fluorescent dye, to migrate to human gastric cancer MKN45 cells in vitro and in vivo. We then used hMSC in which a gene expressed the prodrug-activating enzyme CD, which can convert the prodrug 5-FC into the cytotoxic agent 5-fluorouracil (5-FU), and further investigated the potential of these cells to deliver the CD gene and to reduce tumor growth in nude mice. The migratory capacity of hMSC was confirmed by an in vitro migration assay, as well as in an in vivo model of nude mice bearing subcutaneous tumors of MKN45 cells when hMSC were injected. RESULTS The migration ability of hMSC towards MKN45 cells was confirmed by migration assay. Effective conversion of 5-FC to 5-FU by hMSC transfected with the CD gene (CD-hMSC) showed therapeutic anticancer potential in a MKN45 cell co-culture system, as confirmed by thin layer chromatography. Nude mice bearing MKN45 tumors were intravenously injected with CD-hMSC, followed by systemic 5-FC treatment (500 mg/kg/day) for 7 days. Tumor volumes and weights of mice injected with CD-hMSC decreased significantly after treatment with 5-FC. However, the 5-FC-treated group without CD-hMSC injection showed neither a decrease in tumor volume nor bodyweight loss. CONCLUSION The CD-hMSC system showed anticancer therapeutic potential, and minimized the side-effects of 5-FU.
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Affiliation(s)
- Mi-Hyeon You
- Department of Veterinary Pathology, Seoul National University, Seoul, Korea
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Abstract
The potential application for stem cell therapy is vast, and development for use in ischaemic stroke is still in its infancy. Access to stem cells for research is contentious; however, stem cells are obtainable from both animal and human. Despite a limited understanding of their mechanisms of action, clinical trials assessing stem cells in human stroke have been performed. Trials are also underway evaluating haematopoietic precursors mobilised with granulocyte-colony stimulating factor, an approach offering an autologous means of administrating stem cells for therapeutic purposes. This review summarises current knowledge in regard to stem cells and their potential for helping improve recovery after stroke.
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Affiliation(s)
- Tim England
- Stroke Trials Unit, Institute of Neuroscience, University of Nottingham, Nottingham, UK
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Dharmasaroja P. Bone marrow-derived mesenchymal stem cells for the treatment of ischemic stroke. J Clin Neurosci 2008; 16:12-20. [PMID: 19017556 DOI: 10.1016/j.jocn.2008.05.006] [Citation(s) in RCA: 110] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2008] [Revised: 05/12/2008] [Accepted: 05/17/2008] [Indexed: 02/01/2023]
Abstract
Bone marrow-derived mesenchymal stem cells (MSCs) have great potential as therapeutic agents in stroke management, since they are easily accessible and can be rapidly expanded ex vivo for autologous transplantation. Increasing evidence suggests that bone marrow cells migrate throughout the brain and differentiate into neurons and glial cells. Both non-human and human MSCs have been used to treat stroke in murine models with satisfactory results. Several factors, such as transdifferentiation, induction of neurogenesis and angiogenesis, neuroprotection, and activation of endogenous neurorestorative processes, contribute to the benefits of MSCs in the ischemic brain. Many variables, including types of MSCs, cell dose, timing of treatment, route of cell delivery, and characteristics of stroke patients, influence the efficacy of MSC treatment of stroke. Although the first trials of autologous MSC therapy in stroke patients showed promising results, the optimal approach for different clinical settings has yet to be determined. The fundamental properties of MSCs and their potential short-term and long-term toxicities also need to be determined before moving forward to use of these cells in clinical practice.
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Affiliation(s)
- Permphan Dharmasaroja
- Department of Anatomy and Center for Neuroscience, Faculty of Science, Mahidol University, Rama VI Road, Rajthevi, Bangkok 10400, Thailand.
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