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Xu Z, Song R, Chen Z, Sun Y, Xia Y, Miao H, Wang W, Zhang Y, Jiang X, Chen G. Hydrogen generators-protected mesenchymal stem cells reverse articular redox imbalance-induced immune dysfunction for osteoarthritis treatment. Biomaterials 2025; 320:123239. [PMID: 40054376 DOI: 10.1016/j.biomaterials.2025.123239] [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: 10/26/2024] [Revised: 02/07/2025] [Accepted: 03/03/2025] [Indexed: 04/06/2025]
Abstract
Stem cell therapy has revolutionized the management of osteoarthritis (OA), but the articular dysregulated redox status diminishes cell engraftment efficiency and disrupts immune homeostasis, therefore compromising the overall therapeutic efficacy. Here, we present hydrogen (H2) generators-backpacked mesenchymal stem cells (MSCs) which preserve the biological functions and survival of transplanted cells and reverse articular immune dysfunction, mitigating OA. Specifically, post systemic transplantation, H2 generators-laden MSCs home to OA joints, and upon stimulation in acidic OA environment, H2 produced from the generators remodels articular redox balance, thereby relieving the loss of mitochondrial membrane potential, decreasing cell apoptosis rate, and maintaining pluripotent and paracrine functions of MSCs. Furthermore, the reactive oxygen species scavenging by H2 in combination with paracrine effects of the MSCs promote macrophage polarization towards the anti-inflammatory M2 phenotype, which contributes to reversing synovial immune disorder. In severe OA model, the backpacked MSCs reduce osteoarthritic degeneration, osteophyte formation and joint inflammation, and promote cartilage regeneration. In sum, our work demonstrates that arming with H2 generators effectively boosts the therapeutic efficacy of MSCs, which hold great potential for alleviating redox imbalance-related tissue lesions, including but not limited to OA.
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Affiliation(s)
- Zhou Xu
- Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, 266024, China; Shandong Provincial Key Medical and Health Laboratory of Neuro-oncology of Innovative Integrated Medicine, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao, Qingdao, 266024, China; Northern Jiangsu People's Hospital, Yangzhou, 225001, China; Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China
| | - Ruilong Song
- Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China
| | - Zhiling Chen
- Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, 266024, China
| | - Yu Sun
- Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225001, China
| | - Yinhe Xia
- Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China
| | - Haixiang Miao
- Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225001, China
| | - Weijie Wang
- Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, 266024, China
| | - Yuankai Zhang
- Department of Orthopaedic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
| | - Xinyi Jiang
- NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
| | - Gang Chen
- Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, 266024, China; Shandong Provincial Key Medical and Health Laboratory of Neuro-oncology of Innovative Integrated Medicine, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao, Qingdao, 266024, China; State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing 210023, China.
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Ibrahim MFG, Ali FF, Ali SFES, Shaker ES, Mahmoud HI, Abdellatif FEM, Mokhemer SA. Neuroprotective effect of red dragon fruit extract ameliorates oxidative stress and inflammation in D-galactose-induced aging rat model: biochemical, histological and immunohistochemical study. J Mol Histol 2024; 56:51. [PMID: 39707017 DOI: 10.1007/s10735-024-10316-z] [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: 03/21/2024] [Accepted: 09/17/2024] [Indexed: 12/23/2024]
Abstract
Aging is a worldwide socioeconomic burden. Cerebellar aging is an enigma contributing to many behavioral aging disorders, hence is its hindering by prophylactic measurements is a crucial geriatric research target. Red dragon fruit (RDF) is a tropical fruit with antioxidant, anti-inflammatory and anti-apoptotic properties. This study aimed to determine the protective effect of RDF extract against cerebellar aging. Thirty-two male albino rats were randomly allocated into 4 groups: Control, RDF, aged and RDF-aged groups. Aged group revealed structural distortion affecting cerebellar layers including a significant (P < 0.05) decrease in Purkinje cells number and decrease in granular cell layer thickness by comparison to the control and RDF groups. Additionally, distorted capillary endothelium, and defective myelination were noticed. Interestingly, cerebellar active caspase-3, iNOS, MDA and 3-NT and serum TNF-α levels significantly increased with aging by comparison to the control and RDF groups (all P < 0.05). Biochemical analysis revealed a significant (P < 0.05) decrease in cerebellar SOD and serum GSH levels in aged rats. RDF extract remarkably ameliorated most of the neuronal degenerative changes with a significant (P < 0.05) increase in Purkinje cells numbers, and granular cell layer thickness by comparison to the aged group. Furthermore, it resulted in a significant (P < 0.05) decrease in cerebellum expression of active caspase-3, iNOS, MDA, 3-NT, and serum TNF-α levels associated with a significant (P < 0.05) increase in cerebellar SOD and serum GSH levels by comparison to the aged group. To the best of our knowledge this is the first study showing a neuroprotective effect for RDF against cerebellar aging. RDF might be effective in attenuation of age-induced cerebellar degenerative changes through its anti-apoptotic, antioxidant and anti-inflammatory effects.
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Affiliation(s)
| | - Fatma F Ali
- Medical Physiology Department, Faculty of Medicine, Minia University, Minia, Egypt
- Biochemistry, Molecular Biology and Physiology Department, Faculty of Medicine, Mutah University, Al-Karak, Jordan
| | | | - Emad S Shaker
- Agric. Chemistry Department, Faculty of Agriculture, Minia University, Minia, Egypt
| | - Hemdan I Mahmoud
- Agric. Chemistry Department, Faculty of Agriculture, Minia University, Minia, Egypt
| | | | - Sahar A Mokhemer
- Histology and Cell Biology Department, Faculty of Medicine, Minia University, Minia, Egypt.
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Abd-Elwahab SAE, Khamis NH, Rifaai RA, El-Tahawy NFG, Ibrahim RA. Mesenchymal-Stem Cell-Derived Conditioned Media Versus Exosomes in the Treatment of Rat Model of Polycystic Ovary: An Attempt to Understand the Underlying Mechanisms (Biochemical and Histological Study). MICROSCOPY AND MICROANALYSIS : THE OFFICIAL JOURNAL OF MICROSCOPY SOCIETY OF AMERICA, MICROBEAM ANALYSIS SOCIETY, MICROSCOPICAL SOCIETY OF CANADA 2023; 29:1244-1257. [PMID: 37749691 DOI: 10.1093/micmic/ozad046] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 02/24/2023] [Accepted: 03/28/2023] [Indexed: 09/01/2023]
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common endocrine and reproductive disorders throughout female reproductive age. Cell free therapy [conditioned media (CM) & exosomes (EXO)] is a promising approach in regenerative medicine. This study aimed to compare between the therapeutic effects of stem cell-derived CM and exosomes on induced animal model of polycystic ovary. Polycystic ovary (PCO) was induced in female rats (3-4 weeks old, weighing 70-80 g) by letrozole with a dose of 1 mg/kg/day dissolved in carboxymethylcellulose 1% orally once daily for 5 weeks. Animals were divided into four groups: control group, PCO group, EXO-treated group, and CM-treated group. Serum levels of testosterone hormone, leutinizing hormone, follicle stimulatimg hormone, and insulin hormone were estimated. Immunohistochemistry using anti-P53, anti-AMP-dependent protein kinase antibodies were done. Six rats/group were used for matting with adult male rats for testing fertility. The results showed that CM had significant superior therapeutic effects on exosomes in restoring the normal histological architecture of the ovary and fertility. In summary, cell free treatment is a safe approach for tissue regeneration. Stem cell-derived CM was more effective than exosomes in restoring normal histological structure of the ovaries and fertility in animal models of polycystic ovary.
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Affiliation(s)
- Soha Abd-Elkawy Abd-Elwahab
- Histology and Cell Ciology Department, Faculty of Medicine, Minia University, Cairo-Aswan Agricultural Road, Minia 61519, Egypt
| | - Noura Hassan Khamis
- Histology and Cell Ciology Department, Faculty of Medicine, Minia University, Cairo-Aswan Agricultural Road, Minia 61519, Egypt
| | - Rehab Ahmed Rifaai
- Histology and Cell Ciology Department, Faculty of Medicine, Minia University, Cairo-Aswan Agricultural Road, Minia 61519, Egypt
| | - Nashwa Fathy Gamal El-Tahawy
- Histology and Cell Ciology Department, Faculty of Medicine, Minia University, Cairo-Aswan Agricultural Road, Minia 61519, Egypt
| | - Randa Ahmed Ibrahim
- Histology and Cell Ciology Department, Faculty of Medicine, Minia University, Cairo-Aswan Agricultural Road, Minia 61519, Egypt
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Mokhemer SA, Desouky MK, Abdelghany AK, Ibrahim MFG. Stem cells therapeutic effect in a reserpine-induced fibromyalgia rat model: A possible NLRP3 inflammasome modulation with neurogenesis promotion in the cerebral cortex. Life Sci 2023; 325:121784. [PMID: 37196857 DOI: 10.1016/j.lfs.2023.121784] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 05/06/2023] [Accepted: 05/14/2023] [Indexed: 05/19/2023]
Abstract
Fibromyalgia is a chronic pain syndrome with a multifactorial pathophysiology affecting 2-8 % of the population. AIMS To investigate the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) against fibromyalgia-related cerebral cortex damage and the possible underlying mechanisms of action. MATERIALS AND METHODS Rats were randomly allocated into three groups; control, fibromyalgia and fibromyalgia treated with BMSCs groups. Physical and behavioural assessments were performed. Cerebral cortices were collected for biochemical and histological assessment. KEY FINDINGS Fibromyalgia group showed behavioural changes indicating presence of pain, fatigue, depression, and sleep disturbances. Moreover, biochemical biomarkers alterations were demonstrated by a significant decrease in brain monoamines and GSH levels, but MDA, NO, TNF-alpha, HMGB-1, NLRP3, and caspase-1 levels significantly increased. Furthermore, histological assessment revealed structural and ultrastructural alterations indicating neuronal and neuroglial degeneration with microglia activation, an increase in mast cell number and IL-1β immune-expression. Additionally, a significant decrease in Beclin-1 immune-expression, and blood brain barrier disruption were noticed. Interestingly, BMSCs administration significantly improved behavioural alterations, restored the reduced brain monoamines and oxidative stress markers, and reduced TNF-alpha, HMGB-1, NLRP3, and caspase-1 levels. Profoundly, cerebral cortices demonstrated improved histological structure, significant decrease in mast cell number and IL-1β immune-expression, besides a significant increase in Beclin-1 and DCX immune-expression. SIGNIFICANCE For the best of our knowledge, this is the first study showing ameliorative effects for BMSCs treatment in fibromyalgia-related cerebral cortical damage. The neurotherapeutic effects of BMSCs could be attributed to NLRP3 inflammasome signaling pathway inhibition, mast cell deactivation, and stimulation of neurogenesis and autophagy.
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Affiliation(s)
- Sahar A Mokhemer
- Department of Histology and Cell Biology, Faculty of Medicine, Minia University, 61511 El-Minia, Egypt.
| | - Maha K Desouky
- Department of Anatomy, Faculty of Medicine, Minia University, 61511 El-Minia, Egypt
| | - Asmaa K Abdelghany
- Animal and Poultry Management and Wealth Development Department, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef 62511, Egypt
| | - Manar Fouli Gaber Ibrahim
- Department of Histology and Cell Biology, Faculty of Medicine, Minia University, 61511 El-Minia, Egypt
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Song WP, Jin LY, Zhu MD, Wang H, Xia DS. Clinical trials using dental stem cells: 2022 update. World J Stem Cells 2023; 15:31-51. [PMID: 37007456 PMCID: PMC10052340 DOI: 10.4252/wjsc.v15.i3.31] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/20/2023] [Accepted: 03/08/2023] [Indexed: 03/23/2023] Open
Abstract
For nearly 20 years, dental stem cells (DSCs) have been successfully isolated from mature/immature teeth and surrounding tissue, including dental pulp of permanent teeth and exfoliated deciduous teeth, periodontal ligaments, dental follicles, and gingival and apical papilla. They have several properties (such as self-renewal, multidirectional differentiation, and immunomodulation) and exhibit enormous potential for clinical applications. To date, many clinical articles and clinical trials using DSCs have reported the treatment of pulpitis, periapical lesions, periodontitis, cleft lip and palate, acute ischemic stroke, and so on, and DSC-based therapies obtained satisfactory effects in most clinical trials. In these studies, no adverse events were reported, which suggested the safety of DSC-based therapy. In this review, we outline the characteristics of DSCs and summarize clinical trials and their safety as DSC-based therapies. Meanwhile, we also present the current limitations and perspectives of DSC-based therapy (such as harvesting DSCs from inflamed tissue, applying DSC-conditioned medium/DSC-derived extracellular vesicles, and expanding-free strategies) to provide a theoretical basis for their clinical applications.
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Affiliation(s)
- Wen-Peng Song
- Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Lu-Yuan Jin
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China
| | - Meng-Di Zhu
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China
| | - Hao Wang
- Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Deng-Sheng Xia
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China.
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Sun Y, Xu H, Tan B, Yi Q, Liu H, Tian J, Zhu J. Andrographolide-treated bone marrow mesenchymal stem cells-derived conditioned medium protects cardiomyocytes from injury by metabolic remodeling. Mol Biol Rep 2023; 50:2651-2662. [PMID: 36641493 DOI: 10.1007/s11033-023-08250-6] [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: 06/02/2022] [Accepted: 01/04/2023] [Indexed: 01/15/2023]
Abstract
BACKGROUND Bone marrow mesenchymal stem cells (BMSCs) transplantation therapy providing a great hope for the recovery of myocardial ischemic hypoxic injury. However, the microenvironment after myocardial injury is not conducive to the survival of BMSCs, which limits the therapeutic application of BMSCs. Our previous study has confirmed that the survival of BMSCs cells in the glucose and serum deprivation under hypoxia (GSDH) is increased after Andrographolide (AG) pretreatment, but whether this treatment could improve the effect of BMSCs in repairing of myocardial injury has not been verified. METHODS AND RESULT We first treated H9C2 with GSDH to simulate the microenvironment of myocardial injury in vitro, then we pretreated rat primary BMSCs with AG, and collected conditioned medium derived from BMSCs (BMSCs-CM) and conditioned medium derived from AG-pretreated BMSCs (AG-BMSCs-CM) after GSDH treatment. And they were used to treat H9C2 cells under GSDH to further detect oxidative stress and metabolic changes. The results showed that AG-BMSCs-CM could be more advantageous for cardiomyocyte injury repair than BMSCs-CM, as indicated by the decrease of apoptosis rate and oxidative stress. The changes of mitochondria and lipid droplets results suggested that AG-BMSCs-CM can regulate metabolic remodeling of H9C2 cells to repair cell injury, and that AMPK was activated during this process. CONCLUSIONS This study demonstrates, for the first time, the protective effect of AG-BMSCs-CM on GSDH-induced myocardial cell injury, providing a potential therapeutic strategy for clinical application.
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Affiliation(s)
- Yanting Sun
- Department of Pediatric Research Institute, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, 136 Zhongshan Er Road, Chongqing, 400014, China.,Centre of Clinical Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Hao Xu
- Department of Pediatric Research Institute, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, 136 Zhongshan Er Road, Chongqing, 400014, China.,Department of Clinical Laboratory, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Bin Tan
- Department of Pediatric Research Institute, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, 136 Zhongshan Er Road, Chongqing, 400014, China
| | - Qin Yi
- Department of Pediatric Research Institute, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, 136 Zhongshan Er Road, Chongqing, 400014, China
| | - Huiwen Liu
- Department of Pediatric Research Institute, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, 136 Zhongshan Er Road, Chongqing, 400014, China
| | - Jie Tian
- Department of Pediatric Research Institute, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, 136 Zhongshan Er Road, Chongqing, 400014, China.,Department of Cardiovascular (Internal Medicine), Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Jing Zhu
- Department of Pediatric Research Institute, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, 136 Zhongshan Er Road, Chongqing, 400014, China.
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Ardianto C, Shen R, Barus JF, Sasmita PK, Turana Y, Lilis L, Sidharta VM. Secretome as neuropathology-targeted intervention of Parkinson’s disease. Regen Ther 2022; 21:288-293. [PMID: 36092507 PMCID: PMC9441294 DOI: 10.1016/j.reth.2022.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 07/17/2022] [Accepted: 08/04/2022] [Indexed: 12/05/2022] Open
Abstract
Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease, characterized by apoptosis of dopaminergic neurons in substansia nigra pars compacta (SNpc) caused by ⍺-synuclein aggregation. The use of secretomes released by medicinal signaling cells (MSCs) is one the promising preventive approaches that target several mechanisms in the neuropathology of PD. Its components target the lack of neurotrophin factors, proteasome dysfunction, oxidative stress, mitochondrial dysfunction, and at last neuroinflammation via several pathways. The complex and obscure pathology of PD induce the difficulty of the search of potential preventive approach for this disease. We described the potential of secretome of MSC as the novel preventive approach for PD, especially by targeting the said major pathogenesis of PD.
Secretome targets the major pathogenesis of PD. Secretome regulates inflammation by balancing pro- and anti-inflammatory cytokines. Secretome induces autophagy providing cytoprotective effects. Secretome has anti-oxidative, neuroprotective, and neurotrophic due to neurotrophic factors as its component.
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Affiliation(s)
- Christian Ardianto
- Department of Histology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Indonesia
- Master Program in Biomedical Sciences, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Indonesia
| | - Robert Shen
- Master Program in Biomedical Sciences, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Indonesia
| | - Jimmy F.A. Barus
- Master Program in Biomedical Sciences, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Indonesia
- Department of Neurology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Indonesia
| | - Poppy Kristina Sasmita
- Department of Anatomy, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Indonesia
| | - Yuda Turana
- Department of Neurology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Indonesia
| | - Lilis Lilis
- Department of Anatomical Pathology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Indonesia
| | - Veronika Maria Sidharta
- Department of Histology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Indonesia
- Master Program in Biomedical Sciences, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Indonesia
- Corresponding author. Jalan Pluit Raya No. 2, Pluit, Jakarta Utara, Indonesia,
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Ibrahim MFG, Allam FAFA. Potential stem cell-Conditioned medium and their derived exosomes versus omeprazole in treatment of experimental model of gastric ulcer. Acta Histochem 2022; 124:151896. [PMID: 35430431 DOI: 10.1016/j.acthis.2022.151896] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 04/06/2022] [Accepted: 04/07/2022] [Indexed: 12/12/2022]
Abstract
Gastric ulcer is a common frequent clinical problem affecting all age and gender. This work aims to compare between the therapeutic effects of stem cell derived exosomes, stem cells conditioned medium and omeprazole on the healing of gastric ulcer model. Fifty rats were, assigned into 5 groups; control, gastric ulcer, omeprazole-treated, conditioned medium- treated, and exosomes-treated groups. Gastric ulcer was induced by aspirin dissolved in 1% carboxymethyl cellulose at a daily dose of 200 mg/kg for 5 consecutive days. Stomach specimens were obtained for histological, biochemical, and immunohistochemical assessments. The gastric ulcer group revealed widening of the fundic glands lumen containing, exfoliated dead cells. There was a remarkable distortion of the normal histological structure of the gastric mucosa with surface lining epithelial cell sloughing, vascular congestion and inflammatory cell infiltration. Both exosomes and conditioned medium treatments ameliorated almost all of the histopathological changes. Interestingly, the healing effect of exosomes was greater because it restored the histological architecture of gastric mucosa to nearly normal. In conclusion, this work may pave the future for using stem cell derived exosomes as a more convenient and effective adjuvant therapy in gastric ulcer.
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Affiliation(s)
- Manar Fouli Gaber Ibrahim
- Histology and Cell Biology department, Faculty of Medicine, Minia University, 61511 El-Minia, Egypt.
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Kouchakian MR, Baghban N, Moniri SF, Baghban M, Bakhshalizadeh S, Najafzadeh V, Safaei Z, Izanlou S, Khoradmehr A, Nabipour I, Shirazi R, Tamadon A. The Clinical Trials of Mesenchymal Stromal Cells Therapy. Stem Cells Int 2021; 2021:1634782. [PMID: 34745268 PMCID: PMC8566082 DOI: 10.1155/2021/1634782] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 08/22/2021] [Accepted: 10/05/2021] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stromal cells (MSCs) are a heterogeneous population of adult stem cells, which are multipotent and possess the ability to differentiate/transdifferentiate into mesodermal and nonmesodermal cell lineages. MSCs display broad immunomodulatory properties since they are capable of secreting growth factors and chemotactic cytokines. Safety, accessibility, and isolation from patients without ethical concern make MSCs valuable sources for cell therapy approaches in autoimmune, inflammatory, and degenerative diseases. Many studies have been conducted on the application of MSCs as a new therapy, but it seems that a low percentage of them is related to clinical trials, especially completed clinical trials. Considering the importance of clinical trials to develop this type of therapy as a new treatment, the current paper is aimed at describing characteristics of MSCs and reviewing relevant clinical studies registered on the NIH database during 2016-2020 to discuss recent advances on MSC-based therapeutic approaches being used in different diseases.
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Affiliation(s)
- Mohammad Reza Kouchakian
- Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Neda Baghban
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Seyedeh Farzaneh Moniri
- Department of Anatomical Sciences, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mandana Baghban
- Department of Obstetrics and Gynecology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Shabnam Bakhshalizadeh
- Reproductive Development, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
- Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
| | - Vahid Najafzadeh
- Department of Veterinary and Animal Sciences, Anatomy & Biochemistry Section, University of Copenhagen, Copenhagen, Denmark
| | - Zahra Safaei
- Department of Obstetrics and Gynecology, School of Medicine, Amir Al Mo'menin Hospital, Amir Al Mo'menin IVF Center, Arak University of Medical Sciences, Arak, Iran
| | - Safoura Izanlou
- Department of Nursing, School of Nursing, Larestan University of Medical Sciences, Larestan, Iran
| | - Arezoo Khoradmehr
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Iraj Nabipour
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Reza Shirazi
- Department of Anatomy, School of Medical Sciences, Medicine & Health, UNSW Sydney, Sydney, Australia
| | - Amin Tamadon
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
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Insights into the Effects of Mesenchymal Stem Cell-Derived Secretome in Parkinson's Disease. Int J Mol Sci 2020; 21:ijms21155241. [PMID: 32718092 PMCID: PMC7432166 DOI: 10.3390/ijms21155241] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 07/19/2020] [Accepted: 07/22/2020] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cell (MSC)-derived secretome demonstrated therapeutic effects like those reported after MSCs transplantation. MSC-derived secretome may avoid various side effects of MSC-based therapy, comprising undesirable differentiation of engrafted MSCs and potential activation of the allogeneic immune response. MSC-derived secretome comprises soluble factors and encapsulated extravesicles (EVs). MSC-derived EVs comprise microvesicles, apoptotic bodies, and exosomes. In this review, we focus on the recent insights into the effects of MSC-derived secretome in Parkinson’s disease (PD). In particular, MSC-derived secretome and exosomal components counteracted neuroinflammation and enhanced antioxidant capacity and neurotrophic factors expression. In light of the insights reported in this review, MSC-derived secretome or their released exosomes may be used as a potential therapeutic approach or as adjuvant therapy to counteract the disease progression and improve PD symptoms. Also, MSC-derived secretome may be used as a vehicle in cell transplantation approaches to enhance the viability and survival of engrafted cells. Furthermore, since exosomes can cross the blood–brain barrier, they may be used as biomarkers of neural dysfunction. Further studies are necessary to fully characterize the bioactive molecules present in the secretome and to create a new, effective, cell-free therapeutic approach towards a robust clinical outcome for PD patients.
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