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Kom BTD, Ngoupaye GT, Yassi FB, Foutsop AF, Adassi BM, Ngoufack BS, Ngo Bum E. Antidepressant-like effects of the aqueous lyophilizate of the stems and leaves of Momordica foetida (Cucurbitaceae) in rats. IBRO Neurosci Rep 2025; 18:464-475. [PMID: 40162364 PMCID: PMC11952853 DOI: 10.1016/j.ibneur.2025.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Revised: 02/28/2025] [Accepted: 03/08/2025] [Indexed: 04/02/2025] Open
Abstract
M. foetida (Cucurbitaceae) is a perennial climbing herb, known in traditional medicine for the treatment of certain diseases, such as malaria, headaches, skin-related problems and many others. The objective of this work was to evaluate the antidepressant effect of the aqueous lyophilisate of the mixture of leaves and stem of M. foetida. The antidepressant effect of the aqueous lyophilisate of M. foetida at different doses (25 mg/kg, 50 mg/kg and 75 mg/kg) was evaluated in Wistar rats of both sexes submitted to chronic restriction for 14 days, using the forced swimming test, open field test and sucrose preference test. One hour following the last behavioural test, animals were sacrificed and their hippocampi were collected for biochemical assessment of oxidative parameters, including malondialdehyde (MDA), reduced Glutathione (GSH), Catalase activity, superoxide dismutase (SOD) and nitric oxide (NO) as well as monoamines levels including serotonin, noradrenaline and dopamine. The aqueous lyophilisate of M. foetida significantly decreased the immobility time and significantly increased sucrose consumption (P < 0.001), with no alteration of locomotor activity. The aqueous lyophilisate of M. foetida significantly increased the concentrations of GSH, SOD, as well as catalase activity, while reducing the concentrations of MDA and NO at all doses (P < 0.001). M. foetida at the doses 25 mg/kg and 50 mg/kg significantly increased the concentration of serotonin and dopamine. Only the dose 75 mg/kg significantly increased the concentration of noradrenaline (p < 0.001). These results suggest that M. foetida exerts antidepressant-like effects through the modulation of oxidative stress and monoaminergic pathways.
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Affiliation(s)
| | - Gwladys Temkou Ngoupaye
- Department of Animal Biology, Animal Physiology and Phytopharmacology Research Unit, University of Dschang, Dschang, Cameroon
| | - Francis Bray Yassi
- Department of Biological Sciences, Faculty of Science, University of Ngaoundéré, Ngaoundéré, Cameroon
| | - Aurelien Fossueh Foutsop
- Department of Animal Biology, Animal Physiology and Phytopharmacology Research Unit, University of Dschang, Dschang, Cameroon
| | - Blesdel Maxwell Adassi
- Department of Biological sciences, Faculty of Science, University of Maroua, Maroua, Cameroon
| | - Brunel Steve Ngoufack
- Department of Animal Biology, Animal Physiology and Phytopharmacology Research Unit, University of Dschang, Dschang, Cameroon
| | - Elisabeth Ngo Bum
- Department of Biological sciences, Faculty of Science, University of Maroua, Maroua, Cameroon
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Xiong Z, Chen P, Wang Z, Yao L, Yuan M, Liu P, Sun M, Shu K, Jiang Y. Human umbilical cord-derived mesenchymal stem cells attenuate liver fibrosis by inhibiting hepatocyte ferroptosis through mitochondrial transfer. Free Radic Biol Med 2025; 231:163-177. [PMID: 40023296 DOI: 10.1016/j.freeradbiomed.2025.02.045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Revised: 02/25/2025] [Accepted: 02/26/2025] [Indexed: 03/04/2025]
Abstract
Liver fibrosis is a reversible dynamic pathological process induced by chronic liver injury. Without intervention, liver fibrosis can progress to become cirrhosis, liver failure, or hepatocellular carcinoma, thus posing a high global health burden. Therefore, effective therapies for liver fibrosis are urgently required. Although transplantation of mesenchymal stem cells (MSCs) has significant value as a treatment strategy for liver damage, the underlying mechanisms remain unclear. Chronic liver injury progression is significantly influenced by hepatocyte ferroptosis, and targeting ferroptosis is emerging as a potential treatment strategy for liver fibrosis. Here, we showed that the infusion of human umbilical cord-derived MSCs (hUC-MSCs) alleviated TAA-induced liver fibrosis, improved liver functionality, and decreased ferroptosis in mice. hUC-MSCs inhibit ferroptosis-related mitochondrial damage and lipid peroxidation in AML12 cells in vitro. Mechanistically, under oxidative stress, hUC-MSCs transfer healthy mitochondria to damaged hepatocytes through tunneling nanotubes (TNTs). Cytochalasin D (CytoD), an inhibitor of TNT formation, abrogated the protective effects of hUC-MSCs against ferroptosis. This research emphasizes the ability of hUC-MSCs to serve as a promising treatment for liver fibrosis via mitochondrial transfer through TNTs.
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Affiliation(s)
- Zhiyu Xiong
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
| | - Ping Chen
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
| | - Zheng Wang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
| | - Lichao Yao
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
| | - Mengqin Yuan
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430060, China.
| | - Pingji Liu
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
| | - Muhua Sun
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
| | - Kan Shu
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
| | - Yingan Jiang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
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Yang Y, Deng C, Aldali F, Huang Y, Luo H, Liu Y, Huang D, Cao X, Zhou Q, Xu J, Li Y, Chen H. Therapeutic Approaches and Potential Mechanisms of Small Extracellular Vesicles in Treating Vascular Dementia. Cells 2025; 14:409. [PMID: 40136659 PMCID: PMC11941715 DOI: 10.3390/cells14060409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Revised: 02/26/2025] [Accepted: 03/10/2025] [Indexed: 03/27/2025] Open
Abstract
Small extracellular vesicles (sEVs), including exosomes as a subtype, with a diameter typically less than 200 nm and originating from the endosomal system, are capable of transporting a diverse array of bioactive molecules, including proteins, nucleic acids, and lipids, thereby facilitating intercellular communication and modulating cellular functions. Vascular dementia (VaD) represents a form of cognitive impairment attributed to cerebrovascular disease, characterized by a complex and multifaceted pathophysiological mechanism. Currently, the therapeutic approach to VaD predominantly emphasizes symptom management, as no specific pharmacological treatment exists to cure the condition. Recent investigations have illuminated the significant role of sEVs in the pathogenesis of vascular dementia. This review seeks to provide a comprehensive analysis of the characteristics and functions of sEVs, with a particular focus on their involvement in vascular dementia and its underlying mechanisms. The objective is to advance the understanding of the interplays between sEVs and vascular dementia, thereby offering novel insights for future research and therapeutic strategies.
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Affiliation(s)
- Yujie Yang
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Chunchu Deng
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Fatima Aldali
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Yunjie Huang
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Hongmei Luo
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Yizhou Liu
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Danxia Huang
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Xiaojian Cao
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Qiuzhi Zhou
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Jia Xu
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
- Stem Cell Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Yajie Li
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Hong Chen
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
- Stem Cell Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
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Maria MKM, Abdel Moniem EM, Hanafy AK, Farag DBE, Radwan IA, Abbass MMS, El Moshy S, Rady D, Dörfer CE, Fawzy El-Sayed KM. Age-Related Oral and Para-Oral Tissue Disorders: The Evolving Therapeutic and Diagnostic Potential of Exosomes. Dent J (Basel) 2025; 13:106. [PMID: 40136734 PMCID: PMC11941486 DOI: 10.3390/dj13030106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 02/14/2025] [Accepted: 02/24/2025] [Indexed: 03/27/2025] Open
Abstract
This review highlights the key molecular and cellular mechanisms contributing to aging, such as DNA damage, mitochondrial dysfunction, telomere shortening, protein dysfunction, and defective autophagy. These biological mechanisms are involved in various oral health conditions prevalent in the elderly, including periodontal disease, oral cancer, xerostomia, dental caries, and temporomandibular joint disorders. Exosomes generated by mesenchymal stem cells possess substantial therapeutic potential. These exosomes are nanosized extracellular vesicles derived from cells and are involved in essential intercellular communication and tissue homeostasis. The exosome-based therapies proved superior to traditional cell-based approaches, due to lower immunogenicity, ease of storage, and avoidance of complications associated with cell transplantation. Furthermore, the diagnostic potential of exosomes as non-invasive biomarkers for aging processes and age-related oral diseases offers insights into disease diagnosis, staging, and monitoring. Among the challenges and future perspectives of translating exosome research from preclinical studies to clinical applications is the need for standardized procedures to fully harness the therapeutic and diagnostic capabilities of exosomes.
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Affiliation(s)
- Mohamed Khaled Mohamed Maria
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
| | | | - Ahmed Khaled Hanafy
- Oral Biology Department, Faculty of Dentistry, Egyptian Russian University, Badr City 11829, Egypt;
| | - Dina B. E. Farag
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
| | - Israa Ahmed Radwan
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 12588, Egypt
| | - Marwa M. S. Abbass
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 12588, Egypt
| | - Sara El Moshy
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 12588, Egypt
| | - Dina Rady
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 12588, Egypt
| | - Christof E. Dörfer
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, 24118 Kiel, Germany;
| | - Karim M. Fawzy El-Sayed
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 12588, Egypt
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, 24118 Kiel, Germany;
- Oral Medicine and Periodontology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt
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Mahnoor, Malik K, Kazmi A, Sultana T, Raja NI, Bibi Y, Abbas M, Badruddin IA, Ali MM, Bashir MN. A mechanistic overview on green assisted formulation of nanocomposites and their multifunctional role in biomedical applications. Heliyon 2025; 11:e41654. [PMID: 39916856 PMCID: PMC11800088 DOI: 10.1016/j.heliyon.2025.e41654] [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: 06/12/2024] [Revised: 01/01/2025] [Accepted: 01/02/2025] [Indexed: 02/09/2025] Open
Abstract
The importance of nanocomposites constantly attains attention because of their unique properties all across the fields especially in medical perspectives. The study of green-synthesized nanocomposites has grown to be extremely fascinating in the field of research. Nanocomposites are more promising than mono-metallic nanoparticles because they exhibit synergistic effects. This review encapsulates the current development in the formulation of plant-mediated nanocomposites by using several plant species and the impact of secondary metabolites on their biocompatible functioning. Phyto-synthesis produces diverse nanomaterials with biocompatibility, environment-friendliness, and in vivo actions, characterized by varying sizes, shapes, and biochemical nature. This process is advantageous to conventional physical and chemical procedures. New studies have been conducted to determine the biomedical efficacy of nanocomposites against various diseases. Unfortunately, there has been inadequate investigation into green-assisted nanocomposites. Incorporating phytosynthesized nanocomposites in therapeutic interventions not only enhances healing processes but also augments the host's immune defenses against infections. This review highlights the phytosynthesis of nanocomposites and their various biomedical applications, including antibacterial, antidiabetic, antiviral, antioxidant, antifungal, anti-cancer, and other applications, as well as their toxicity. This review also explores the mechanistic action of nanocomposites to achieve their designated tasks. Biogenic nanocomposites for multimodal imaging have the potential to exchange the conventional methods and materials in biomedical research. Well-designed nanocomposites have the potential to be utilized in various biomedical fields as innovative theranostic agents with the subsequent objective of efficiently diagnosing and treating a variety of human disorders.
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Affiliation(s)
- Mahnoor
- Department of Botany, PMAS, Arid Agriculture University Rawalpindi, Pakistan
| | - Khafsa Malik
- Department of Botany, PMAS, Arid Agriculture University Rawalpindi, Pakistan
| | - Abeer Kazmi
- The State Key Laboratory of Freshwater Ecology and Biotechnology, The Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, Hubei, PR China
- University of Chinese Academy of Sciences, Beijing, 100049, PR China
| | - Tahira Sultana
- Department of Botany, PMAS, Arid Agriculture University Rawalpindi, Pakistan
| | - Naveed Iqbal Raja
- Department of Botany, PMAS, Arid Agriculture University Rawalpindi, Pakistan
| | - Yamin Bibi
- Department of Botany, Rawalpindi Women University, Rawalpindi, Pakistan
| | - Mazhar Abbas
- Department of Biochemistry, University of Veterinary and Animal Science Lahore (Jhang Campus), Jhang, 35200, Pakistan
| | - Irfan Anjum Badruddin
- Mechanical Engineering Department, College of Engineering, King Khalid University, Abha, 61421, Saudi Arabia
| | - M. Mahmood Ali
- Department of Mechatronic Engineering, Atlantic Technological University Sligo, Ash Lane, F91 YW50, Sligo, Ireland
| | - Muhammad Nasir Bashir
- Department of Mechanical Engineering, Yonsei University, Seoul, 120-749, Republic of Korea
- National University of Sciences and Technology, Islamabad, Pakistan
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Ganesh BH, Padinjarathil H, Rajendran RL, Ramani P, Gangadaran P, Ahn BC. The Role of Extracellular Vesicles in Aging and Age-Related Disorders. Antioxidants (Basel) 2025; 14:177. [PMID: 40002364 PMCID: PMC11851802 DOI: 10.3390/antiox14020177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 01/18/2025] [Accepted: 01/31/2025] [Indexed: 02/27/2025] Open
Abstract
A variety of molecular and cellular changes distinguish the multifaceted biological process of aging. Recent studies in this decade have demonstrated the essential role of extracellular vesicles (EVs) in the aging process. Mitochondrial malfunction and increased oxidative stress are major contributors for the aging process. This review investigates the role of EVs in intercellular communication, tissue regeneration, and inflammation in the context of aging. We also discuss the exosome and its utility to reduce oxidative stress, which is a key part of aging, as well as the possibility of using the exosomes (EVs) as anti-aging drugs. Changes in cargo composition can influence the aging phenotype and impact the functionality of cells and tissues. Additionally, the role of EVs in oxidative stress during the aging process addresses potential treatment strategies and the development of biomarkers for age-associated disorders. The review also highlighted the role of exosomes in providing antioxidant properties, which help reduce excessive reactive oxygen species (ROS) and strengthen cellular defenses against oxidative stress. Additionally, it emphasized the role of extracellular vesicles (EVs) in age-related pathologies, such as neurodegenerative diseases, cardiovascular disorders, and immunosenescence, offering insights into targeted interventions for promoting healthy aging. This article provides a comprehensive analysis of the current body of knowledge regarding the therapeutic effects of EVs on aging, with a particular emphasis on the implications of this emerging field of research and its relationship to oxidative stress.
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Affiliation(s)
- Bharathi Hassan Ganesh
- Dhanvanthri Laboratory, Department of Chemistry, Amrita School of Physical Sciences, Amrita Vishwa Vidyapeetham, Coimbatore 641112, India; (B.H.G.); (H.P.)
- Center of Excellence in Advanced Materials and Green Technologies (CoE-AMGT), Amrita School of Engineering, Amrita Vishwa Vidyapeetham, Coimbatore 641112, India
| | - Himabindu Padinjarathil
- Dhanvanthri Laboratory, Department of Chemistry, Amrita School of Physical Sciences, Amrita Vishwa Vidyapeetham, Coimbatore 641112, India; (B.H.G.); (H.P.)
- Center of Excellence in Advanced Materials and Green Technologies (CoE-AMGT), Amrita School of Engineering, Amrita Vishwa Vidyapeetham, Coimbatore 641112, India
| | - Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; (R.L.R.); (P.G.)
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
- Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Prasanna Ramani
- Dhanvanthri Laboratory, Department of Chemistry, Amrita School of Physical Sciences, Amrita Vishwa Vidyapeetham, Coimbatore 641112, India; (B.H.G.); (H.P.)
- Center of Excellence in Advanced Materials and Green Technologies (CoE-AMGT), Amrita School of Engineering, Amrita Vishwa Vidyapeetham, Coimbatore 641112, India
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; (R.L.R.); (P.G.)
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
- Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Byeong-Cheol Ahn
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; (R.L.R.); (P.G.)
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
- Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea
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Ezati M, Hashemi A, Zumberg I, Nasr MP, Fohlerova Z. In Vitro Assessment of Chitosan-PEG Hydrogels Enriched with MSCs-Exosomes for Enhancing Wound Healing. Macromol Biosci 2025:e2400609. [PMID: 39838702 DOI: 10.1002/mabi.202400609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 01/06/2025] [Indexed: 01/23/2025]
Abstract
Regenerating skin tissue remains a major challenge in medical science, especially due to the risk of scarring and prolonged healing, which becomes even more complicated in people with diabetes. Recent advancements have led to the creation of therapeutic dressings incorporating drug-delivery systems to tackle these issues. Exosomes (Exos) derived from mesenchymal stem cells (MSCs) have gained significant attention for mediating therapy without directly using cells, thanks to their natural anti-inflammatory and tissue repair properties mirroring those of MSCs. In this study, an advanced wound dressing combines chitosan (CS) and polyethylene glycol (PEG) hydrogel with adipose MSCs-derived Exos (ADMSCs-Exos). This composite, formed using a straightforward blending technique, is engineered to improve the healing process of severe skin injuries by steadily releasing Exos as the hydrogel degrades. The in vitro studies demonstrate that this hydrogel-exosome dressing greatly enhances endothelial cell migration, reduces oxidative stress, and promotes angiogenesis, crucial for effective wound healing. Additionally, real time-polymerase chain reaction (RT-PCR) analysis revealed significant upregulation of key genes involved in these processes, supporting the therapeutic potential of the hydrogel-Exo combination. These findings emphasize the potential of this hydrogel-Exos combination as an innovative and promising solution for advanced wound care.
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Affiliation(s)
- Masoumeh Ezati
- Department of Biomedical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3082/12, Brno, 61600, Czech Republic
| | - Amir Hashemi
- Department of Biomedical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3082/12, Brno, 61600, Czech Republic
| | - Inna Zumberg
- Department of Biomedical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3082/12, Brno, 61600, Czech Republic
| | - Minoo Partovi Nasr
- Department of Biomedical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3082/12, Brno, 61600, Czech Republic
| | - Zdenka Fohlerova
- Department of Biomedical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3082/12, Brno, 61600, Czech Republic
- Department of Microelectronics, Faculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3082/12, Brno, 61600, Czech Republic
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Katahira Y, Horio E, Yamaguchi N, Sonoda J, Yamagishi M, Miyakawa S, Murakami F, Hasegawa H, Mizoguchi I, Yoshimoto T. Protective Effect of Conditioned Medium of Immortalized Human Stem Cells from Exfoliated Deciduous Teeth Against Hair Graying Caused by X-Ray Irradiation via Its Antioxidative Activity. Antioxidants (Basel) 2025; 14:109. [PMID: 39857443 PMCID: PMC11760446 DOI: 10.3390/antiox14010109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 01/15/2025] [Accepted: 01/15/2025] [Indexed: 01/27/2025] Open
Abstract
Hair graying is one of the common visible signs of human aging, resulting from decreased or abolished melanogenesis due to the depletion of melanocyte stem cells through excess accumulation of oxidative stress. Cell-free therapy using a conditioned medium (CM) of mesenchymal stem cells has been highlighted in the field of regenerative medicine owing to its potent therapeutic effects with lower regulatory hurdles and safety risk. Recently, we demonstrated that a CM of an immortalized stem cell line from human exfoliated deciduous teeth (SHED) has protective effects against a mouse model of ulcer formation via antioxidative and angiogenic activities mediated by HGF and VEGF. However, to date, no effective treatments for hair graying have been developed, and the effect of SHED-CM on hair graying remains unknown. In this study, we have investigated the effect of SHED-CM on a hair graying mouse model caused by X-ray irradiation. Repetitive subcutaneous administrations of SHED-CM greatly suppressed the development of hair graying, when compared to control medium, resulting in reduced cutaneous expression of 8-hydroxy-2'-deoxyguanosine, the major product of DNA damage induced by reactive oxygen species. Consistent with these in vivo results, SHED-CM significantly inhibited the cell death caused by X-ray irradiation in melanoma cell line B16F10 cells. Immunodepletion of HGF or VEGF in the SHED-CM revealed that this inhibition was due to suppression of the generation of reactive oxygen species, which was mainly mediated by HGF and probably VEGF. These results suggest that SHED-CM has protective effects against hair graying via its antioxidative activity.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Takayuki Yoshimoto
- Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan; (Y.K.)
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9
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Huete-Acevedo J, Mas-Bargues C, Arnal-Forné M, Atencia-Rabadán S, Sanz-Ros J, Borrás C. Role of Redox Homeostasis in the Communication Between Brain and Liver Through Extracellular Vesicles. Antioxidants (Basel) 2024; 13:1493. [PMID: 39765821 PMCID: PMC11672896 DOI: 10.3390/antiox13121493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 11/21/2024] [Accepted: 11/29/2024] [Indexed: 01/11/2025] Open
Abstract
Extracellular vesicles (EVs) are small, membrane-bound particles secreted by cells into the extracellular environment, playing an increasingly recognized role in inter-organ communication and the regulation of various physiological processes. Regarding the redox homeostasis context, EVs play a pivotal role in propagating and mitigating oxidative stress signals across different organs. Cells under oxidative stress release EVs containing signaling molecules that can influence the redox status of distant cells and tissues. EVs are starting to be recognized as contributors to brain-liver communication. Therefore, in this review, we show how redox imbalance can affect the release of EVs in the brain and liver. We propose EVs as mediators of redox homeostasis in the brain-liver axis.
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Affiliation(s)
- Javier Huete-Acevedo
- MiniAging Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, CIBERFES, INCLIVA, Avenida Blasco Ibáñez, 15, 46010 Valencia, Spain; (J.H.-A.); (C.M.-B.); (M.A.-F.); (S.A.-R.)
| | - Cristina Mas-Bargues
- MiniAging Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, CIBERFES, INCLIVA, Avenida Blasco Ibáñez, 15, 46010 Valencia, Spain; (J.H.-A.); (C.M.-B.); (M.A.-F.); (S.A.-R.)
| | - Marta Arnal-Forné
- MiniAging Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, CIBERFES, INCLIVA, Avenida Blasco Ibáñez, 15, 46010 Valencia, Spain; (J.H.-A.); (C.M.-B.); (M.A.-F.); (S.A.-R.)
| | - Sandra Atencia-Rabadán
- MiniAging Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, CIBERFES, INCLIVA, Avenida Blasco Ibáñez, 15, 46010 Valencia, Spain; (J.H.-A.); (C.M.-B.); (M.A.-F.); (S.A.-R.)
| | - Jorge Sanz-Ros
- Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA;
| | - Consuelo Borrás
- MiniAging Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, CIBERFES, INCLIVA, Avenida Blasco Ibáñez, 15, 46010 Valencia, Spain; (J.H.-A.); (C.M.-B.); (M.A.-F.); (S.A.-R.)
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10
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Wang W, Ren Y, Yu Q, Jiang L, Yu C, Yue Z, Wang Y, Lu J, Che P, Li J, Sun H. Biodegradable exosome-engineered hydrogels for the prevention of peritoneal adhesions via anti-oxidation and anti-inflammation. Mater Today Bio 2024; 29:101312. [PMID: 39525394 PMCID: PMC11550211 DOI: 10.1016/j.mtbio.2024.101312] [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: 04/23/2024] [Revised: 08/16/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024] Open
Abstract
Peritoneal adhesions (PA) are a common and severe complication after abdominal surgery, impacting millions of patients worldwide. The use of anti-adhesion materials as physical barriers is an effective strategy to prevent postoperative adhesions. However, the local inflammatory microenvironment exerts a significant impact on the efficacy of anti-adhesion therapies. In this study, an injectable hydrogel based on oxidized dextran/carboxymethyl chitosan (DCC) is designed and prepared. Furthermore, the DCC hydrogel is specifically engineered to load the adipose mesenchymal stem cells (ADSCs)-derived exosomes (Exos) for the treatment of PA. The prepared DCC hydrogel can act as the physical barrier via covering the irregular wound surface effectively. Moreover, it shows controlled degradation property, enabling the regulated release of Exos. The DCC hydrogel loaded Exos (DCC/Exo) system has high antioxidant capacity, and can effectively modulate the inflammatory microenvironments and diminish apoptosis. Notably, it promotes a polarization shift towards the M2-like phenotype in macrophages. The RNA-seq analysis confirms that the DCC/Exo system exhibits significant anti-inflammatory properties and promotes a reduction in collagen deposition. Consequently, the DCC/Exo system can inhibit peritoneal adhesions significantly in a mouse cecum-abdominal wall injury model. These results demonstrate the DCC/Exo is an ideal material for preventing postoperative adhesions.
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Affiliation(s)
- Weitong Wang
- Department of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063210, China
| | - Yuchen Ren
- Department of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063210, China
| | - Qingyu Yu
- Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering, Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China
| | - Lijie Jiang
- Department of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063210, China
| | - Chaojie Yu
- Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering, Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China
| | - Zhiwei Yue
- Department of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063210, China
| | - Yue Wang
- Department of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063210, China
| | - Jiajun Lu
- Department of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063210, China
| | - Pengcheng Che
- School of Nursing and Rehabilitation, North China University of Science and Technology, Tangshan, 063210, China
| | - Junjie Li
- Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering, Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China
| | - Hong Sun
- Department of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063210, China
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11
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Wu H, Qian X, Liang G. The Role of Small Extracellular Vesicles Derived from Mesenchymal Stromal Cells on Myocardial Protection: a Review of Current Advances and Future Perspectives. Cardiovasc Drugs Ther 2024; 38:1111-1122. [PMID: 37227567 PMCID: PMC10209575 DOI: 10.1007/s10557-023-07472-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/18/2023] [Indexed: 05/26/2023]
Abstract
Small extracellular vesicles (SEVs) secreted by mesenchymal stromal cells (MSCs) are considered one of the most promising biological therapies in recent years. The protective effect of MSCs-derived SEVs on myocardium is mainly related to their ability to deliver cargo, anti-inflammatory properties, promotion of angiogenesis, immunoregulation, and other factors. Herein, this review focuses on the biological properties, isolation methods, and functions of SEVs. Then, the roles and potential mechanisms of SEVs and engineered SEVs in myocardial protection are summarized. Finally, the current situation of clinical research on SEVs, the difficulties encountered, and the future fore-ground of SEVs are discussed. In conclusion, although there are some technical difficulties and conceptual contradictions in the research of SEVs, the unique biological functions of SEVs provide a new direction for the development of regenerative medicine. Further exploration is warranted to establish a solid experimental and theoretical basis for future clinical application of SEVs.
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Affiliation(s)
- Hongkun Wu
- School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou China
- Center for Translational Medicine, Guizhou Medical University, Guiyang, Guizhou China
- Department of Cardiac Surgery, Guizhou Provincial People’s Hospital, Guiyang, Guizhou China
| | - Xingkai Qian
- Center for Translational Medicine, Guizhou Medical University, Guiyang, Guizhou China
- Department of Cardiac Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou China
| | - Guiyou Liang
- Department of Cardiac Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou China
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12
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Ge Z, Qiu C, Zhou J, Yang Z, Jiang T, Yuan W, Yu L, Li J. Proteomic analysis of human Wharton's jelly mesenchymal stem/stromal cells and human amniotic epithelial stem cells: a comparison of therapeutic potential. Sci Rep 2024; 14:28061. [PMID: 39543366 PMCID: PMC11564572 DOI: 10.1038/s41598-024-79063-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 11/06/2024] [Indexed: 11/17/2024] Open
Abstract
Perinatal stem cells have prominent applications in cell therapy and regenerative medicine. Among them, human Wharton's jelly mesenchymal stem/stromal cells (hWJMSCs) and human amniotic epithelial stem cells (hAESCs) have been widely used. However, the distinction in the therapeutic potential of hWJMSCs and hAESCs is poorly understood. In this study, we reported the phenotypic differences between these two distinct cell types and provided the first systematic comparison of their therapeutic potential in terms of immunomodulation, extracellular matrix (ECM) remodelling, angiogenesis and antioxidative stress using proteomics. The results revealed that the two cell types presented different protein expression profiles and were both promising candidates for cell therapy. Both types of cells demonstrated angiogenic and antifibrotic potential, whereas hAESCs presented superior immunological tolerance and antioxidant properties, which were supported by a series of relevant in vitro assays. Our study provides clues for the selection of appropriate cell types for diverse indications in cell therapy, which contributes to the advancement of their clinical translation and application.
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Affiliation(s)
- Zhen Ge
- Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, 310013, Zhejiang, China
| | - Chen Qiu
- Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine of Sir Run Run Shaw Hospital, Zhejiang University-Lishui Joint Innovation Center for Life and Health, Zhejiang University, Hangzhou, 310058, China
- College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, 314400, China
| | - Jiayi Zhou
- Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine of Sir Run Run Shaw Hospital, Zhejiang University-Lishui Joint Innovation Center for Life and Health, Zhejiang University, Hangzhou, 310058, China
- College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, 314400, China
| | - Zhuoheng Yang
- Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine of Sir Run Run Shaw Hospital, Zhejiang University-Lishui Joint Innovation Center for Life and Health, Zhejiang University, Hangzhou, 310058, China
- College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, 314400, China
| | - Tuoying Jiang
- Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine of Sir Run Run Shaw Hospital, Zhejiang University-Lishui Joint Innovation Center for Life and Health, Zhejiang University, Hangzhou, 310058, China
- College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, 314400, China
| | - Weixin Yuan
- College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, 314400, China
| | - Luyang Yu
- Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine of Sir Run Run Shaw Hospital, Zhejiang University-Lishui Joint Innovation Center for Life and Health, Zhejiang University, Hangzhou, 310058, China.
- College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, 314400, China.
| | - Jinying Li
- Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine of Sir Run Run Shaw Hospital, Zhejiang University-Lishui Joint Innovation Center for Life and Health, Zhejiang University, Hangzhou, 310058, China.
- College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, 314400, China.
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13
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El Assaad N, Chebly A, Salame R, Achkar R, Bou Atme N, Akouch K, Rafoul P, Hanna C, Abou Zeid S, Ghosn M, Khalil C. Anti-aging based on stem cell therapy: A scoping review. World J Exp Med 2024; 14:97233. [PMID: 39312703 PMCID: PMC11372738 DOI: 10.5493/wjem.v14.i3.97233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Revised: 07/04/2024] [Accepted: 07/18/2024] [Indexed: 08/29/2024] Open
Abstract
Stem cells are present in the tissues and organs and remain in a quiescent and undifferentiated state until it is physiologically necessary to produce new descendant cells. Due to their multipotency property, mesenchymal stem cells have attracted considerable attention worldwide due to their immunomodulation and therapeutic function in tissue regeneration. Stem cells secrete components such as paracrine factors, extracellular vesicles, and exosomes which have been shown to have anti-inflammatory, anti-aging, reconstruction and wound healing potentials in many in vitro and in vivo models. The pluripotency and immunomodulatory features of stem cells could potentially be an effective tool in cell therapy and tissue repair. Aging affects the capacity for self-renewal and differentiation of stem cells, decreasing the potential for regeneration and the loss of optimal functions in organisms over time. Current progress in the field of cellular therapy and regenerative medicine has facilitated the evolution of particular guidelines and quality control approaches, which eventually lead to clinical trials. Cell therapy could potentially be one of the most promising therapies to control aging due to the fact that single stem cell transplantation can regenerate or substitute the injured tissue. To understand the involvement of stem cells not only in tissue maintenance and disease but also in the control of aging it is important to know and identify their properties, functions, and regulation in vivo, which are addressed in this review.
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Affiliation(s)
- Nassar El Assaad
- Faculty of Medicine, Saint Joseph University, Beirut 961, Lebanon
| | - Alain Chebly
- Centre Jacques Loiselet for Medical Genetics and Genomics (CGGM), Faculty of Medicine, Saint Joseph University, Beirut 961, Lebanon
- Higher Institute of Public Health, Saint Joseph University, Beirut 961, Lebanon
| | - Rawad Salame
- Stem Cell Therapy Lab, Reviva Regenerative Medicine Center, Beirut 961, Lebanon
| | - Robert Achkar
- Poz Pozan University of Medical Sciences, Pozan 034, Poland
| | - Nour Bou Atme
- Faculty of Medicine, Saint Joseph University, Beirut 961, Lebanon
| | - Khalil Akouch
- Stem Cell Therapy Lab, Reviva Regenerative Medicine Center, Beirut 961, Lebanon
| | - Paul Rafoul
- Department of Epidemiology and Biostatistics, Faculty of Public Health, Lebanese University, Beirut 961, Lebanon
| | - Colette Hanna
- School of Medicine, Lebanese American University, Beirut 961, Lebanon
| | - Samer Abou Zeid
- Faculty of Medicine, Saint Joseph University, Beirut 961, Lebanon
| | - Marwan Ghosn
- Faculty of Medicine, Saint Joseph University, Beirut 961, Lebanon
| | - Charbel Khalil
- Stem Cell Therapy Lab, Reviva Regenerative Medicine Center, Beirut 961, Lebanon
- School of Medicine, Lebanese American University, Beirut 961, Lebanon
- Bone Marrow Transplant Unit, Burjeel Medical City, Abu Dhabi 999041, United Arab Emirates
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14
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Wang J, Zhang M, Wang H. Emerging Landscape of Mesenchymal Stem Cell Senescence Mechanisms and Implications on Therapeutic Strategies. ACS Pharmacol Transl Sci 2024; 7:2306-2325. [PMID: 39144566 PMCID: PMC11320744 DOI: 10.1021/acsptsci.4c00284] [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: 05/15/2024] [Revised: 07/05/2024] [Accepted: 07/09/2024] [Indexed: 08/16/2024]
Abstract
Mesenchymal stem cells (MSCs) hold significant promise for regenerative medicine and tissue engineering due to their unique multipotent differentiation ability and immunomodulatory properties. MSC therapy is widely discussed and utilized in clinical treatment. However, during both in vitro expansion and in vivo transplantation, MSCs are prone to senescence, an irreversible growth arrest characterized by morphological, gene expression, and functional changes in genomic regulation. The microenvironment surrounding MSCs plays a crucial role in modulating their senescence phenotype, influenced by factors such as hypoxia, inflammation, and aging status. Numerous strategies targeting MSC senescence have been developed, including senolytics and senomorphic agents, antioxidant and exosome therapies, mitochondrial transfer, and niche modulation. Novel approaches addressing replicative senescence have also emerged. This paper comprehensively reviews the current molecular manifestations of MSC senescence, addresses the environmental impact on senescence, and highlights potential therapeutic strategies to mitigate senescence in MSC-based therapies. These insights aim to enhance the efficacy and understanding of MSC therapies.
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Affiliation(s)
- Jing Wang
- Department
of Cellular and Molecular Medicine, University
of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States
| | - Muqing Zhang
- Institute
of Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, Maryland, 21215, United States
| | - Hu Wang
- Institute
of Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, Maryland, 21215, United States
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15
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Jin H, Liu J, Wang D. Antioxidant Potential of Exosomes in Animal Nutrition. Antioxidants (Basel) 2024; 13:964. [PMID: 39199210 PMCID: PMC11351667 DOI: 10.3390/antiox13080964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 08/05/2024] [Accepted: 08/06/2024] [Indexed: 09/01/2024] Open
Abstract
This review delves into the advantages of exosomes as novel antioxidants in animal nutrition and their potential for regulating oxidative stress. Although traditional nutritional approaches promote oxidative stress defense systems in mammalian animals, several issues remain to be solved, such as low bioavailability, targeted tissue efficiency, and high-dose by-effect. As an important candidate offering regulation opportunities concerned with cellular communication, disease prevention, and physiology regulation in multiple biological systems, the potential of exosomes in mediating redox status in biological systems has not been well described. A previously reported relationship between redox system regulation and circulating exosomes suggested exosomes as a fundamental candidate for both a regulator and biomarker for a redox system. Herein, we review the effects of oxidative stress on exosomes in animals and the potential application of exosomes as antioxidants in animal nutrition. Then, we highlight the advantages of exosomes as redox regulators due to their higher bioavailability and physiological heterogeneity-targeted properties, providing a theoretical foundation and feed industry application. Therefore, exosomes have shown great potential as novel antioxidants in the field of animal nutrition. They can overcome the limitations of traditional antioxidants in terms of dosage and side effects, which will provide unprecedented opportunities in nutritional management and disease prevention, and may become a major breakthrough in the field of animal nutrition.
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Affiliation(s)
| | | | - Diming Wang
- Institute of Dairy Science, MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; (H.J.); (J.L.)
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16
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Li L, Wang Y, Xu Y, Xu J, Zhao Y, Cheng Z, Fang Y, Miao Y, Zhang X. ROS-scavenging lipid-based liquid crystalline as a favorable stem cell extracellular vesicles delivery vector to promote wound healing. J Control Release 2024; 371:298-312. [PMID: 38815703 DOI: 10.1016/j.jconrel.2024.05.048] [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: 02/20/2024] [Revised: 05/23/2024] [Accepted: 05/27/2024] [Indexed: 06/01/2024]
Abstract
Wound management is a critical clinical challenge due to the dynamic and complex pathological characteristics of inflammation, proliferation, and matrix remodeling. To address this challenge, the regulation and management of this multi-stage pathological microenvironment may provide a feasible approach to wound healing. In this work, we synthesized a new lipid material (DA) with reactive oxygen species (ROS) scavenging effect to prepare DA-based liquid crystalline (DALC). Then, DALC was incorporated with adipose mesenchymal stem cells-derived extracellular vesicles (AMSC-EVs) to fabricate a novel scaffold dressing (EVs@DALC) for the treatment of the wound. DALC not only endowed EVs@DALC with ROS scavenging sites for relieving the oxidative stress and inflammation in the microenvironment of the wound site, but also facilitated cellular uptake and transfection of microRNA and growth factors contained in AMSC-EVs. Benefiting from DALC, AMSC-EVs effectively transferred microRNA and growth factors into the skin cells to induce cell proliferation and migration and accelerate angiogenesis. The results of wound healing effect in vivo indicate EVs@DALC achieved multi-stage pathological modulation for accelerating wound healing through alleviating inflammation, promoting cell proliferation and migration, and angiogenesis. Taken together, this work provides an effective strategy based on antioxidant lipid liquid crystalline delivering extracellular vesicles in treating skin wounds and paves a way for stem cell extracellular vesicles clinical translation.
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Affiliation(s)
- Lijun Li
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Ying Wang
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yuqi Xu
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Jian Xu
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yanqi Zhao
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Zijian Cheng
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yuelin Fang
- Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, China
| | - Yunqiu Miao
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Xinxin Zhang
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, China.
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17
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Karamanidou T, Krommydas K, Karanikou M, Tsamos D, Michalakis K, Kletsas D, Tsouknidas A, Pratsinis H. Biological Activities of Citrus-Derived Extracellular Vesicles on Human Cells: The Role of Preservation. Curr Issues Mol Biol 2024; 46:5812-5824. [PMID: 38921018 PMCID: PMC11203058 DOI: 10.3390/cimb46060347] [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: 04/20/2024] [Revised: 06/03/2024] [Accepted: 06/04/2024] [Indexed: 06/27/2024] Open
Abstract
Extracellular vesicles (EVs) have been identified as important mediators for cell-to-cell communication. Citrus-based EVs in particular offer an excellent platform for nutraceutical delivery systems, as their endemic cargo includes micronutrients (e.g., ascorbic acid), which contribute to their antioxidant capacity. Despite being extensively investigated as to their therapeutic and diagnostic potential, their cargo is inherently unstable and thus directly affected by their storage and preservation. In this study, EVs were isolated from citrus fruit using tangential flow filtration and evaluated for their physicochemical characteristics, antioxidant activity and effects on human cells. To assess how their isolation and preservation methods affect these properties, the EVs were tested immediately after isolation (from fresh and freeze-thawed juices) or following freeze-drying. A measurable biological effect of cryoprotection on citrus-derived EVs was evident, whether during or after isolation. This was more pronounced in the cell-based assays, ranging from -4% to +32% in human skin fibroblast proliferation. Nevertheless, the effects on human cancer cells varied depending on the cell line. Although these results should be considered preliminary observations, subject to further investigation, it is safe to state that any type of preservation is expected to impact the EVs' biological activity.
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Affiliation(s)
- Theodora Karamanidou
- Laboratory for Biomaterials and Computational Mechanics, Department of Mechanical Engineering, University of Western Macedonia, 50100 Kozani, Greece (K.K.); (D.T.)
| | - Konstantinos Krommydas
- Laboratory for Biomaterials and Computational Mechanics, Department of Mechanical Engineering, University of Western Macedonia, 50100 Kozani, Greece (K.K.); (D.T.)
| | - Maria Karanikou
- Laboratory for Biomaterials and Computational Mechanics, Department of Mechanical Engineering, University of Western Macedonia, 50100 Kozani, Greece (K.K.); (D.T.)
- Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research “Demokritos”, 15341 Athens, Greece;
| | - Dimitrios Tsamos
- Laboratory for Biomaterials and Computational Mechanics, Department of Mechanical Engineering, University of Western Macedonia, 50100 Kozani, Greece (K.K.); (D.T.)
| | - Konstantinos Michalakis
- Department of Restorative Sciences & Biomaterials, Henry M. Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA;
| | - Dimitris Kletsas
- Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research “Demokritos”, 15341 Athens, Greece;
| | - Alexander Tsouknidas
- Laboratory for Biomaterials and Computational Mechanics, Department of Mechanical Engineering, University of Western Macedonia, 50100 Kozani, Greece (K.K.); (D.T.)
- Department of Restorative Sciences & Biomaterials, Henry M. Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA;
| | - Harris Pratsinis
- Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research “Demokritos”, 15341 Athens, Greece;
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18
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El-Akabawy G, El-Kersh SOF, El-Kersh AOFO, Amin SN, Rashed LA, Abdel Latif N, Elshamey A, Abdallah MAAEM, Saleh IG, Hein ZM, El-Serafi I, Eid N. Dental pulp stem cells ameliorate D-galactose-induced cardiac ageing in rats. PeerJ 2024; 12:e17299. [PMID: 38799055 PMCID: PMC11127642 DOI: 10.7717/peerj.17299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 04/03/2024] [Indexed: 05/29/2024] Open
Abstract
BACKGROUND Ageing is a key risk factor for cardiovascular disease and is linked to several alterations in cardiac structure and function, including left ventricular hypertrophy and increased cardiomyocyte volume, as well as a decline in the number of cardiomyocytes and ventricular dysfunction, emphasizing the pathological impacts of cardiomyocyte ageing. Dental pulp stem cells (DPSCs) are promising as a cellular therapeutic source due to their minimally invasive surgical approach and remarkable proliferative ability. AIM This study is the first to investigate the outcomes of the systemic transplantation of DPSCs in a D-galactose (D-gal)-induced rat model of cardiac ageing. Methods. Thirty 9-week-old Sprague-Dawley male rats were randomly assigned into three groups: control, ageing (D-gal), and transplanted groups (D-gal + DPSCs). D-gal (300 mg/kg/day) was administered intraperitoneally daily for 8 weeks. The rats in the transplantation group were intravenously injected with DPSCs at a dose of 1 × 106 once every 2 weeks. RESULTS The transplanted cells migrated to the heart, differentiated into cardiomyocytes, improved cardiac function, upregulated Sirt1 expression, exerted antioxidative effects, modulated connexin-43 expression, attenuated cardiac histopathological alterations, and had anti-senescent and anti-apoptotic effects. CONCLUSION Our results reveal the beneficial effects of DPSC transplantation in a cardiac ageing rat model, suggesting their potential as a viable cell therapy for ageing hearts.
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Affiliation(s)
- Gehan El-Akabawy
- Department of Basic Medical Sciences, College of Medicine, Ajman University, Ajman, United Arab Emirates
- Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
- Department of Anatomy and Embryology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | | | | | - Shaimaa Nasr Amin
- Department of Anatomy, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan
- Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Laila Ahmed Rashed
- Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Noha Abdel Latif
- Department of Medical Pharmacology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Medical Pharmacology, Armed Forces College of Medicine, Cairo, Egypt
| | - Ahmed Elshamey
- Samanoud General Hospital, Samannoud City, Samanoud, Gharbia, Egypt
| | | | - Ibrahim G. Saleh
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Sinai University, Kantra, Ismailia, Egypt
| | - Zaw Myo Hein
- Department of Basic Medical Sciences, College of Medicine, Ajman University, Ajman, United Arab Emirates
- Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
| | - Ibrahim El-Serafi
- Department of Basic Medical Sciences, College of Medicine, Ajman University, Ajman, United Arab Emirates
| | - Nabil Eid
- Department of Anatomy, Division of Human Biology, School of Medicine, International Medical University, Kuala Lumpur, Malaysia
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19
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Zhou Y, Huang J, Zeng L, Yang Q, Bai F, Mai Q, Deng K. Human mesenchymal stem cells derived exosomes improve ovarian function in chemotherapy-induced premature ovarian insufficiency mice by inhibiting ferroptosis through Nrf2/GPX4 pathway. J Ovarian Res 2024; 17:80. [PMID: 38622725 PMCID: PMC11017636 DOI: 10.1186/s13048-024-01403-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 03/30/2024] [Indexed: 04/17/2024] Open
Abstract
BACKGROUND Chemotherapy exposure has become a main cause of premature ovarian insufficiency (POI). This study aimed to evaluate the role and molecular mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hUMSC-Exos) in ovarian function protection after chemotherapy. METHODS hUMSC-Exos were applied to cyclophosphamide-induced premature ovarian insufficiency mice and human ovarian granulosa tumor cells (KGN) to determine their effects on follicular development and granulosa cell apoptosis. Evaluation was done for iron ion and reactive oxygen species (ROS) production, lipid peroxidation levels, and changes in iron death-related molecules (nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Glutathione Peroxidase enzyme 4 (GPX4), and Solute carrier family 7 member 11 cystine glutamate transporter (SLC7A11; xCT)). Furthermore, rescue experiments using an Nrf2 inhibitor were performed to assess the therapeutic effects of hUMSC-Exos on granulosa cells. RESULTS hUMSC-Exos promoted ovarian hormone levels and primary follicle development in POI mice and reduced granulosa cell apoptosis. After hUMSC-Exos treatment, the ROS production, free iron ions and lipid peroxidation levels of granulosa cells decreased, and the iron death marker proteins Nrf2, xCT and GPX4 also decreased. Furthermore, the Nrf2 inhibitor ML385 significantly attenuated the effects of hUMSC-Exos on granulosa cells. CONCLUSION hUMSC-Exos inhibit ferroptosis and protect against CTX-induced ovarian damage and granulosa cell apoptosis through the Nrf2/GPX4 signaling pathway, revealing a novel mechanism of hUMSC-Exos in POI therapy.
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Affiliation(s)
- Yuan Zhou
- Department of Gynecology, Shunde Hospital, Southern Medical University, Foshan, Guangdong, 528308, China
| | - Jinfa Huang
- Department of Gynecology, Shunde Hospital, Southern Medical University, Foshan, Guangdong, 528308, China
| | - Lingling Zeng
- Department of Gynecology, Shunde Hospital, Southern Medical University, Foshan, Guangdong, 528308, China
| | - Qian Yang
- Department of Gynecology, Shunde Hospital, Southern Medical University, Foshan, Guangdong, 528308, China
| | - Fangjuan Bai
- Department of Gynecology, Shunde Hospital, Southern Medical University, Foshan, Guangdong, 528308, China
| | - Qiqing Mai
- Department of Gynecology, Shunde Hospital, Southern Medical University, Foshan, Guangdong, 528308, China
| | - Kaixian Deng
- Department of Gynecology, Shunde Hospital, Southern Medical University, Foshan, Guangdong, 528308, China.
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20
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Cui X, Dong H, Luo S, Zhuang B, Li Y, Zhong C, Ma Y, Hong L. Long Non-Coding RNA-Cardiac-Inducing RNA 6 Mediates Repair of Infarcted Hearts by Inducing Mesenchymal Stem Cell Differentiation into Cardiogenic Cells through Cyclin-Dependent Kinase 1. Int J Mol Sci 2024; 25:3466. [PMID: 38542439 PMCID: PMC10971150 DOI: 10.3390/ijms25063466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 03/08/2024] [Accepted: 03/13/2024] [Indexed: 04/04/2024] Open
Abstract
This study aims to investigate the induction effect of LncRNA-CIR6 on MSC differentiation into cardiogenic cells in vitro and in vivo. In addition to pretreatment with Ro-3306 (a CDK1 inhibitor), LncRNA-CIR6 was transfected into BMSCs and hUCMSCs using jetPRIME. LncRNA-CIR6 was further transfected into the hearts of C57BL/6 mice via 100 μL of AAV9-cTnT-LncRNA-CIR6-ZsGreen intravenous injection. After three weeks of transfection followed by AMI surgery, hUCMSCs (5 × 105/100 μL) were injected intravenously one week later. Cardiac function was evaluated using VEVO 2100 and electric mapping nine days after cell injection. Immunofluorescence, Evans blue-TTC, Masson staining, FACS, and Western blotting were employed to determine relevant indicators. LncRNA-CIR6 induced a significant percentage of differentiation in BMSCs (83.00 ± 0.58)% and hUCMSCs (95.43 ± 2.13)% into cardiogenic cells, as determined by the expression of cTnT using immunofluorescence and FACS. High cTNT expression was observed in MSCs after transfection with LncRNA-CIR6 by Western blotting. Compared with the MI group, cardiac contraction and conduction function in MI hearts treated with LncRNA-CIR6 or combined with MSCs injection groups were significantly increased, and the areas of MI and fibrosis were significantly lower. The transcriptional expression region of LncRNA-CIR6 was on Chr17 from 80209290 to 80209536. The functional region of LncRNA-CIR6 was located at nucleotides 0-50/190-255 in the sequence. CDK1, a protein found to be related to the proliferation and differentiation of cardiomyocytes, was located in the functional region of the LncRNA-CIR6 secondary structure (from 0 to 17). Ro-3306 impeded the differentiation of MSCs into cardiogenic cells, while MSCs transfected with LncRNA-CIR6 showed a high expression of CDK1. LncRNA-CIR6 mediates the repair of infarcted hearts by inducing MSC differentiation into cardiogenic cells through CDK1.
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Affiliation(s)
| | | | | | | | | | | | | | - Lan Hong
- Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China; (X.C.); (H.D.); (S.L.); (B.Z.); (Y.L.); (C.Z.); (Y.M.)
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21
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Liu Z, Cheng L, Zhang L, Shen C, Wei S, Wang L, Qiu Y, Li C, Xiong Y, Zhang X. Emerging role of mesenchymal stem cells-derived extracellular vesicles in vascular dementia. Front Aging Neurosci 2024; 16:1329357. [PMID: 38389559 PMCID: PMC10881761 DOI: 10.3389/fnagi.2024.1329357] [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: 10/28/2023] [Accepted: 01/24/2024] [Indexed: 02/24/2024] Open
Abstract
Vascular dementia (VD) is a prevalent cognitive disorder among the elderly. Its pathological mechanism encompasses neuronal damage, synaptic dysfunction, vascular abnormalities, neuroinflammation, and oxidative stress, among others. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have garnered significant attention as an emerging therapeutic strategy. Current research indicates that MSC-derived extracellular vesicles (MSC-EVs) play a pivotal role in both the diagnosis and treatment of VD. Thus, this article delves into the recent advancements of MSC-EVs in VD, discussing the mechanisms by which EVs influence the pathophysiological processes of VD. These mechanisms form the theoretical foundation for their neuroprotective effect in VD treatment. Additionally, the article highlights the potential applications of EVs in VD diagnosis. In conclusion, MSC-EVs present a promising innovative treatment strategy for VD. With rigorous research and ongoing innovation, this concept can transition into practical clinical treatment, providing more effective options for VD patients.
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Affiliation(s)
- Ziying Liu
- Department of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China
| | - Lin Cheng
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China
- Department of Neurology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China
| | - Lushun Zhang
- Department of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China
| | - Chunxiao Shen
- Department of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China
| | - Shufei Wei
- Department of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China
| | - Liangliang Wang
- Department of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China
| | - Yuemin Qiu
- Department of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China
| | - Chuan Li
- Department of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China
| | - Yinyi Xiong
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China
- Department of Rehabilitation, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China
| | - Xiaorong Zhang
- Department of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China
- Center for Cognitive Science and Transdisciplinary Studies, Jiujiang University, Jiujiang, Jiangxi, China
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Shi H, Yang Z, Cui J, Tao H, Ma R, Zhao Y. Mesenchymal stem cell-derived exosomes: a promising alternative in the therapy of preeclampsia. Stem Cell Res Ther 2024; 15:30. [PMID: 38317195 PMCID: PMC10845755 DOI: 10.1186/s13287-024-03652-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 01/29/2024] [Indexed: 02/07/2024] Open
Abstract
Preeclampsia (PE) is a common morbid complication during pregnancy, affecting 2%-8% of pregnancies globally and posing serous risks to the health of both mother and fetus. Currently, the only effective treatment for PE is timely termination of pregnancy, which comes with increased perinatal risks. However, there is no effective way to delay pathological progress and improve maternal and fetal outcomes. In light of this, it is of great significance to seek effective therapeutic strategies for PE. Exosomes which are nanoparticles carrying bioactive substances such as proteins, lipids, and nucleic acids, have emerged as a novel vehicle for intercellular communication. Mesenchymal stem cell-derived exosomes (MSC-Exos) participate in various important physiological processes, including immune regulation, cell proliferation and migration, and angiogenesis, and have shown promising potential in tissue repair and disease treatment. Recently, MSC-Exos therapy has gained popularity in the treatment of ischaemic diseases, immune dysfunction, inflammatory diseases, and other fields due to their minimal immunogenicity, characteristics similar to donor cells, ease of storage, and low risk of tumor formation. This review elaborates on the potential therapeutic mechanism of MSC-Exos in treating preeclampsia, considering the main pathogenic factors of the condition, including placental vascular dysplasia, immunological disorders, and oxidative stress, based on the biological function of MSC-Exos. Additionally, we discuss in depth the advantages and challenges of MSC-Exos as a novel acellular therapeutic agent in preeclampsia treatment.
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Affiliation(s)
- Haoran Shi
- Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Zejun Yang
- Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Jianjian Cui
- Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Hui Tao
- Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Ruilin Ma
- Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Yin Zhao
- Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China.
- Shenzhen Huazhong University of Science and Technology Research Institute, Shen Zhen, 518000, China.
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23
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Chen S, Sigdel S, Sawant H, Bihl J, Wang J. Exercise-Intervened Endothelial Progenitor Cell Exosomes Protect N2a Cells by Improving Mitochondrial Function. Int J Mol Sci 2024; 25:1148. [PMID: 38256220 PMCID: PMC10816803 DOI: 10.3390/ijms25021148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 01/10/2024] [Accepted: 01/16/2024] [Indexed: 01/24/2024] Open
Abstract
We have recently demonstrated that exosomal communication between endothelial progenitor cells (EPCs) and brain endothelial cells is compromised in hypertensive conditions, which might contribute to the poor outcomes of stroke subjects with hypertension. The present study investigated whether exercise intervention can regulate EPC-exosome (EPC-EX) functions in hypertensive conditions. Bone marrow EPCs from sedentary and exercised hypertensive transgenic mice were used for generating EPC-EXs, denoted as R-EPC-EXs and R-EPC-EXET. The exosomal microRNA profile was analyzed, and EX functions were determined in a co-culture system with N2a cells challenged by angiotensin II (Ang II) plus hypoxia. EX-uptake efficiency, cellular survival ability, reactive oxygen species (ROS) production, mitochondrial membrane potential, and the expressions of cytochrome c and superoxide-generating enzyme (Nox4) were assessed. We found that (1) exercise intervention improves the uptake efficiency of EPC-EXs by N2a cells. (2) exercise intervention restores miR-27a levels in R-EPC-EXs. (3) R-EPC-EXET improved the survival ability and reduced ROS overproduction in N2a cells challenged with Ang II and hypoxia. (4) R-EPC-EXET improved the mitochondrial membrane potential and decreased cytochrome c and Nox4 levels in Ang II plus hypoxia-injured N2a cells. All these effects were significantly reduced by miR-27a inhibitor. Together, these data have demonstrated that exercise-intervened EPC-EXs improved the mitochondrial function of N2a cells in hypertensive conditions, which might be ascribed to their carried miR-27a.
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Affiliation(s)
| | | | | | | | - Jinju Wang
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA; (S.C.); (S.S.); (H.S.); (J.B.)
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24
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Yang RL, Chen SY, Fu SP, Zhao DZ, Wan WH, Yang K, Lei W, Yang Y, Zhang Q, Zhang T. Antioxidant mechanisms of mesenchymal stem cells and their therapeutic potential in vitiligo. Front Cell Dev Biol 2023; 11:1293101. [PMID: 38178870 PMCID: PMC10764575 DOI: 10.3389/fcell.2023.1293101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 12/08/2023] [Indexed: 01/06/2024] Open
Abstract
Vitiligo is a skin pigmentation disorder caused by melanocyte damage or abnormal function. Reac-tive oxygen species Reactive oxygen species can cause oxidative stress damage to melanocytes, which in turn induces vitiligo. Traditional treatments such as phototherapy, drugs, and other methods of treatment are long and result in frequent recurrences. Currently, mesenchymal stem cells (MSCs) are widely used in the research of various disease treatments due to their excellent paracrine effects, making them a promising immunoregulatory and tissue repair strategy. Furthermore, an increasing body of evi-dence suggests that utilizing the paracrine functions of MSCs can downregulate oxidative stress in the testes, liver, kidneys, and other affected organs in animal models of certain diseases. Addition-ally, MSCs can help create a microenvironment that promotes tissue repair and regeneration in are-as with oxidative stress damage, improving the disordered state of the injured site. In this article, we review the pathogenesis of oxidative stress in vitiligo and promising strategies for its treatment.
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Affiliation(s)
- Rui-lin Yang
- Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Si-yu Chen
- Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Sheng-ping Fu
- Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - De-zhi Zhao
- Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Wei-hong Wan
- Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Kang Yang
- Department of Dermatology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Wei Lei
- Department of Dermatology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Ying Yang
- Department of Dermatology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Qian Zhang
- Department of Human Anatomy, Zunyi Medical University, Zunyi, China
| | - Tao Zhang
- Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Department of Dermatology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
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25
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Hwang JS, Kim J, You GE, Hong IH, Cho IH, Song HB, Shin YJ, Ma DJ. In Vivo Electroporation Improves Retinal Delivery of Intravitreally Injected Exosomes. J Ocul Pharmacol Ther 2023; 39:463-471. [PMID: 37486724 DOI: 10.1089/jop.2023.0016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/25/2023] Open
Abstract
Purpose: Mesenchymal stem cell (MSC)-derived exosomes are promising therapeutic agents and natural nanoscale delivery platforms for treating degenerative retinal diseases. This study investigated the effect of electroporation on the retinal delivery of intravitreally administered MSC-derived exosomes in a murine model. Methods: Exosomes isolated from adipose tissue-derived MSCs were stained with ExoGlow exosome-specific dye and administered to the right eyes of 40 Sprague-Dawley rats. Electroporation was performed in 20 rats immediately after intravitreal injection (electroporation group); 5 square pulses of 40 V/cm for 50 ms each with 950-ms intervals were administered. The remaining 20 rats were assigned to the no-electroporation group. The eyeballs were harvested 24 h later for evaluation. The total number of fluorescent particles per hyperfield was counted from the retinal flat mounts to quantify the retinal delivery of exosomes. Tissue damage after electroporation was evaluated using retinal histological sections and a terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end labeling (TUNEL) assay. Results: A significantly higher number of fluorescent particles per hyperfield were observed in the retinal flat mounts of the electroporation group compared with that in the no-electroporation group (599.0 ± 307.5 vs. 376.9 ± 175.4; P = 0.013). Retinal histological sections and TUNEL assays showed no signs of tissue damage after electroporation. Conclusions: In vivo electroporation can improve the retinal delivery of intravitreally injected exosomes.
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Affiliation(s)
- Jin Sun Hwang
- Department of Ophthalmology, Hallym University Kangnam Sacred Heart Hospital; Seoul, Republic of Korea
- Hallym BioEyeTech Research Center; Hallym University College of Medicine, Seoul, Republic of Korea
| | - Junho Kim
- Research and Development Institute, Biosolution, Seoul, Republic of Korea
| | - Ga Eun You
- Research and Development Institute, Biosolution, Seoul, Republic of Korea
| | - In Hwan Hong
- Department of Ophthalmology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si, Republic of Korea
| | - In Hwan Cho
- Department of Ophthalmology, Soon Chun Hyang University Hospital Cheonan, Cheonan-si, Republic of Korea
| | - Hyun Beom Song
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Young Joo Shin
- Department of Ophthalmology, Hallym University Kangnam Sacred Heart Hospital; Seoul, Republic of Korea
- Hallym BioEyeTech Research Center; Hallym University College of Medicine, Seoul, Republic of Korea
| | - Dae Joong Ma
- Department of Ophthalmology, Hallym University Kangnam Sacred Heart Hospital; Seoul, Republic of Korea
- Hallym BioEyeTech Research Center; Hallym University College of Medicine, Seoul, Republic of Korea
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26
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Dai ZT, Wu YL, Li XR, Liao XH. MKL-1 suppresses ferroptosis by activating system Xc- and increasing glutathione synthesis. Int J Biol Sci 2023; 19:4457-4475. [PMID: 37781038 PMCID: PMC10535709 DOI: 10.7150/ijbs.80666] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 08/09/2023] [Indexed: 10/03/2023] Open
Abstract
Chemotherapy is a standard method in traditional treatment for gastric cancer. It is well known that the anti-tumor effects of chemotherapy are achieved mainly through the direct killing of cancer cells via apoptosis. However, chemotherapy often fails due to drug resistance. Therefore, non-apoptotic cell death induction by ferroptosis has recently been proposed as a new therapeutic modality to ablate cancer. In this study, we determined the role of MKL-1 in ferroptosis. In vitro and in vivo experiments showed that inhibition of MKL-1 expression significantly enhanced cell sensitivity to ferroptosis-inducing agents. It functions by targeting system Xc- to affect the synthesis of GSH in cells. Therefore, we developed an exosome-based therapeutic approach targeting MKL-1, which provides a novel insight into the treatment of gastric cancer.
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Affiliation(s)
- Zhou-Tong Dai
- Department of Gynaecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Centre for Obstetrics and Gynaecology, Cancer Biology Research Centre (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Institute of Biology and Medicine, College of Life and Health Science, Wuhan University of Science and Technology, Wuhan, China
| | - Yong-Lin Wu
- Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xing-Rui Li
- Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xing-Hua Liao
- Institute of Biology and Medicine, College of Life and Health Science, Wuhan University of Science and Technology, Wuhan, China
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Liu M, Chen R, Xu Y, Zheng J, Wang M, Wang P. Exosomal miR-141-3p from PDLSCs Alleviates High Glucose-Induced Senescence of PDLSCs by Activating the KEAP1-NRF2 Signaling Pathway. Stem Cells Int 2023; 2023:7136819. [PMID: 37274022 PMCID: PMC10238146 DOI: 10.1155/2023/7136819] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 04/19/2023] [Accepted: 04/21/2023] [Indexed: 06/06/2023] Open
Abstract
Human periodontal ligament stem cells (PDLSCs) are the most promising stem cells for periodontal tissue engineering. Senescent PDLSCs have diminished abilities to proliferate and differentiate, affecting the efficiency of periodontal tissue repair and regeneration. Stem cell-derived exosomes are important participants in intercellular information exchange and can help ameliorate senescence. In this study, we investigated PDLSC senescence in a high glucose microenvironment as well as the ability of human periodontal ligament stem cell-derived exosomes (PDLSC-Exos) to alleviate cellular senescence and the underlying mechanisms. Herein, PDLSCs and PDLSC-Exos were isolated and extracted. Then, cellular senescence indicators were evaluated after high glucose (25 mM) treatment of cultured PDLSCs. PDLSC-Exos were cocultured with senescent PDLSCs to further explore the role of PDLSC-Exos in cellular senescence and determine the differences in cellular oxidative stress levels after PDLSC-Exo treatment. Next, we investigated whether PDLSC-Exos alleviated cellular senescence by restoring the balance of oxidative stress signals and explored the underlying molecular pathways. We discovered that PDLSCs underwent premature senescence due to high glucose culture, but they were rejuvenated by PDLSC-Exos. The rejuvenating effects of PDLSC-Exos were notably reversed by cotreatment with ML385, an inhibitor of nuclear factor erythroid 2-related factor 2 (NRF2), indicating that this recovery depended on NRF2 activation. Further analyses revealed that microRNA-141-3p (miR-141-3p) was expressed at relatively high levels in PDLSC-Exos and was instrumental in PDLSC-Exo-mediated restoration by downregulating Kelch-like ECH-associated protein 1 (KEAP1), which is a negative regulator of NRF2 expression. Our findings suggest that PDLSC-Exos alleviate high glucose-induced senescence of PDLSCs by transferring miR-141-3p to activate the KEAP1-NRF2 signaling pathway. Based on this research, PDLSC-Exos may behave similarly to their parental PDLSCs and have significant effects on cellular senescence by delivering their encapsulated bioactive chemicals to target cells.
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Affiliation(s)
- Min Liu
- Department of Stomatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Rui Chen
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Yunxuan Xu
- Department of Stomatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Jiawen Zheng
- Department of Stomatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Min Wang
- Department of Stomatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Ping Wang
- Department of Stomatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
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Zhang L, Wu J, Zhu Z, He Y, Fang R. Mitochondrion: A bridge linking aging and degenerative diseases. Life Sci 2023; 322:121666. [PMID: 37030614 DOI: 10.1016/j.lfs.2023.121666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/30/2023] [Accepted: 04/01/2023] [Indexed: 04/10/2023]
Abstract
Aging is a natural process, characterized by progressive loss of physiological integrity, impaired function, and increased vulnerability to death. For centuries, people have been trying hard to understand the process of aging and find effective ways to delay it. However, limited breakthroughs have been made in anti-aging area. Since the hallmarks of aging were summarized in 2013, increasing studies focus on the role of mitochondrial dysfunction in aging and aging-related degenerative diseases, such as neurodegenerative diseases, osteoarthritis, metabolic diseases, and cardiovascular diseases. Accumulating evidence indicates that restoring mitochondrial function and biogenesis exerts beneficial effects in extending lifespan and promoting healthy aging. In this paper, we provide an overview of mitochondrial changes during aging and summarize the advanced studies in mitochondrial therapies for the treatment of degenerative diseases. Current challenges and future perspectives are proposed to provide novel and promising directions for future research.
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Affiliation(s)
- Lanlan Zhang
- Center for Plastic & Reconstructive Surgery, Department of Hand & Reconstructive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Jianlong Wu
- Center for Plastic & Reconstructive Surgery, Department of Hand & Reconstructive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Ziguan Zhu
- Center for Plastic & Reconstructive Surgery, Department of Hand & Reconstructive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yuchen He
- Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; Department of Orthopaedics, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Renpeng Fang
- Center for Plastic & Reconstructive Surgery, Department of Hand & Reconstructive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
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Ji S, Xiong M, Chen H, Liu Y, Zhou L, Hong Y, Wang M, Wang C, Fu X, Sun X. Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases. Signal Transduct Target Ther 2023; 8:116. [PMID: 36918530 PMCID: PMC10015098 DOI: 10.1038/s41392-023-01343-5] [Citation(s) in RCA: 52] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 12/16/2022] [Accepted: 01/19/2023] [Indexed: 03/16/2023] Open
Abstract
The ageing process is a systemic decline from cellular dysfunction to organ degeneration, with more predisposition to deteriorated disorders. Rejuvenation refers to giving aged cells or organisms more youthful characteristics through various techniques, such as cellular reprogramming and epigenetic regulation. The great leaps in cellular rejuvenation prove that ageing is not a one-way street, and many rejuvenative interventions have emerged to delay and even reverse the ageing process. Defining the mechanism by which roadblocks and signaling inputs influence complex ageing programs is essential for understanding and developing rejuvenative strategies. Here, we discuss the intrinsic and extrinsic factors that counteract cell rejuvenation, and the targeted cells and core mechanisms involved in this process. Then, we critically summarize the latest advances in state-of-art strategies of cellular rejuvenation. Various rejuvenation methods also provide insights for treating specific ageing-related diseases, including cellular reprogramming, the removal of senescence cells (SCs) and suppression of senescence-associated secretory phenotype (SASP), metabolic manipulation, stem cells-associated therapy, dietary restriction, immune rejuvenation and heterochronic transplantation, etc. The potential applications of rejuvenation therapy also extend to cancer treatment. Finally, we analyze in detail the therapeutic opportunities and challenges of rejuvenation technology. Deciphering rejuvenation interventions will provide further insights into anti-ageing and ageing-related disease treatment in clinical settings.
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Affiliation(s)
- Shuaifei Ji
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China
| | - Mingchen Xiong
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China
| | - Huating Chen
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China
| | - Yiqiong Liu
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China
| | - Laixian Zhou
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China
| | - Yiyue Hong
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China
| | - Mengyang Wang
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China
| | - Chunming Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macau SAR, China.
| | - Xiaobing Fu
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China.
| | - Xiaoyan Sun
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China.
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Abstract
Oxidative stress is the result of an imbalance between the formation of reactive oxygen species (ROS) and the levels of enzymatic and non-enzymatic antioxidants. The assessment of biological redox status is performed by the use of oxidative stress biomarkers. An oxidative stress biomarker is defined as any physical structure or process or chemical compound that can be assessed in a living being (in vivo) or in solid or fluid parts thereof (in vitro), the determination of which is a reproducible and reliable indicator of oxidative stress. The use of oxidative stress biomarkers allows early identification of the risk of developing diseases associated with this process and also opens up possibilities for new treatments. At the end of the last century, interest in oxidative stress biomarkers began to grow, due to evidence of the association between the generation of free radicals and various pathologies. Up to now, a significant number of studies have been carried out to identify and apply different oxidative stress biomarkers in clinical practice. Among the most important oxidative stress biomarkers, it can be mentioned the products of oxidative modifications of lipids, proteins, nucleic acids, and uric acid as well as the measurement of the total antioxidant capacity of fluids in the human body. In this review, we aim to present recent advances and current knowledge on the main biomarkers of oxidative stress, including the discovery of new biomarkers, with emphasis on the various reproductive complications associated with variations in oxidative stress levels.
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Wang H, Huber CC, Li XP. Mesenchymal and Neural Stem Cell-Derived Exosomes in Treating Alzheimer's Disease. Bioengineering (Basel) 2023; 10:253. [PMID: 36829747 PMCID: PMC9952071 DOI: 10.3390/bioengineering10020253] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 01/19/2023] [Accepted: 01/24/2023] [Indexed: 02/17/2023] Open
Abstract
As the most common form of dementia and a progressive neurodegenerative disorder, Alzheimer's disease (AD) affects over 10% world population with age 65 and older. The disease is neuropathologically associated with progressive loss of neurons and synapses in specific brain regions, deposition of amyloid plaques and neurofibrillary tangles, neuroinflammation, blood-brain barrier (BBB) breakdown, mitochondrial dysfunction, and oxidative stress. Despite the intensive effort, there is still no cure for the disorder. Stem cell-derived exosomes hold great promise in treating various diseases, including AD, as they contain a variety of anti-apoptotic, anti-inflammatory, and antioxidant components. Moreover, stem cell-derived exosomes also promote neurogenesis and angiogenesis and can repair damaged BBB. In this review, we will first outline the major neuropathological features associated with AD; subsequently, a discussion of stem cells, stem cell-secreted exosomes, and the major exosome isolation methods will follow. We will then summarize the recent data involving the use of mesenchymal stem cell- or neural stem cell-derived exosomes in treating AD. Finally, we will briefly discuss the challenges, perspectives, and clinical trials using stem cell-derived exosomes for AD therapy.
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Affiliation(s)
- Hongmin Wang
- Division of Basic Biomedical Sciences and Center for Brain and Behavior Research, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA
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Secretome of hESC-Derived MSC-like Immune and Matrix Regulatory Cells Mitigate Pulmonary Fibrosis through Antioxidant and Anti-Inflammatory Effects. Biomedicines 2023; 11:biomedicines11020463. [PMID: 36830999 PMCID: PMC9953085 DOI: 10.3390/biomedicines11020463] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/01/2023] [Accepted: 02/02/2023] [Indexed: 02/09/2023] Open
Abstract
Oxidative stress and inflammation are major drivers in the pathogenesis and progression of pulmonary fibrosis (PF). The mesenchymal stem cell (MSC) secretome has regenerative potential and immunomodulatory functions. Human embryonic stem cell (hESC)-derived MSC-like immune and matrix regulatory cells (IMRCs) are manufacturable with large-scale good manufacturing practice (GMP) preparation. In the present study, the antioxidative and anti-inflammatory properties and the therapeutic effect of the secretome of hESC-MSC-IMRC-derived conditioned culture medium (CM) (hESC-MSC-IMRC-CM) were investigated. Results revealed the capacities of hESC-MSC-IMRC-CM to reduce bleomycin (BLM)-induced reactive oxygen species (ROS), extracellular matrix (ECM) deposition, and epithelial-mesenchymal transition (EMT) in A549 cells. The administration of concentrated hESC-MSC-IMRC-CM significantly alleviated the pathogenesis of PF in lungs of BLM-injured mice, as accessed by pathohistological changes and the expression of ECM and EMT. A mechanistic study further demonstrated that the hESC-MSC-IMRC-CM was able to inhibit BLM-induced ROS and pro-inflammatory cytokines, accompanied by a reduced expression of Nox4, Nrf2, Ho-1, and components of the Tlr4/MyD88 signaling cascade. These results provide a proof of concept for the hESC-MSC-IMRC-derived secretome treatment of PF, in part mediated by their antioxidative and anti-inflammatory effects. This study thus reinforces the development of ready-to-use, cell-free hESC-MSC-IMRC secretome biomedicine for the treatment of PF in clinical settings.
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Hajinejad M, Ebrahimzadeh MH, Ebrahimzadeh-Bideskan A, Rajabian A, Gorji A, Sahab Negah S. Exosomes and Nano-SDF Scaffold as a Cell-Free-Based Treatment Strategy Improve Traumatic Brain Injury Mechanisms by Decreasing Oxidative Stress, Neuroinflammation, and Increasing Neurogenesis. Stem Cell Rev Rep 2023; 19:1001-1018. [PMID: 36652144 DOI: 10.1007/s12015-022-10483-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/13/2022] [Indexed: 01/19/2023]
Abstract
Traumatic brain injury (TBI) causes a variety of complex pathological changes in brain parenchymal tissue by increasing neuroinflammatory and apoptosis responses. Currently, there is no treatment to resolve the consequences related to TBI. Recently, an extensive literature has grown up around the theme of bystander effects of stem cells, a mechanism of stem cells without the need for cell transplantation, which is called cell-free therapy. The purpose of this investigation was to determine the efficacy of a cell-free-based therapy strategy using exosomes derived from human neural stem cells (hNSCs) and a novel nano-scaffold in rats subjected to TBI. In this study, a series of in vitro and in vivo experiments from behavior tests to gene expression was performed to define the effect of exosomes in combination with a three-dimensional (3D) nano-scaffold containing a bio-motif of SDF1α (Nano-SDF). Application of exosomes with Nano-SDF significantly decreased oxidative stress in serum and brain samples. Moreover, treatment with exosomes and Nano-SDF significantly reduced the expression of Toll-like receptor 4 and its downstream signaling pathway, including NF-kβ and interleukin-1β. We also found that the cell-free-based therapy strategy could decrease reactive gliosis at the injury site. Interestingly, we showed that exosomes with Nano-SDF increased neurogenesis in the sub-ventricular zone of the lateral ventricle, indicating a bio-bridge mechanism. To sum up, the most obvious finding to emerge from this study is that a cell-free-based therapy strategy can be an effective option for future practice in the course of TBI.
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Affiliation(s)
- Mehrdad Hajinejad
- Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Alireza Ebrahimzadeh-Bideskan
- Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. .,Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Arezoo Rajabian
- Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Gorji
- Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.,Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, 48149, Munster, Germany
| | - Sajad Sahab Negah
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. .,Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Pardis Campus, Azadi Square, Kalantari Blvd, Mashhad, Iran.
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Warnecke A, Staecker H, Rohde E, Gimona M, Giesemann A, Szczepek AJ, Di Stadio A, Hochmair I, Lenarz T. Extracellular Vesicles in Inner Ear Therapies-Pathophysiological, Manufacturing, and Clinical Considerations. J Clin Med 2022; 11:jcm11247455. [PMID: 36556073 PMCID: PMC9788356 DOI: 10.3390/jcm11247455] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/09/2022] [Accepted: 12/11/2022] [Indexed: 12/23/2022] Open
Abstract
(1) Background: Sensorineural hearing loss is a common and debilitating condition. To date, comprehensive pharmacologic interventions are not available. The complex and diverse molecular pathology that underlies hearing loss may limit our ability to intervene with small molecules. The current review foccusses on the potential for the use of extracellular vesicles in neurotology. (2) Methods: Narrative literature review. (3) Results: Extracellular vesicles provide an opportunity to modulate a wide range of pathologic and physiologic pathways and can be manufactured under GMP conditions allowing for their application in the human inner ear. The role of inflammation in hearing loss with a focus on cochlear implantation is shown. How extracellular vesicles may provide a therapeutic option for complex inflammatory disorders of the inner ear is discussed. Additionally, manufacturing and regulatory issues that need to be addressed to develop EVs as advanced therapy medicinal product for use in the inner ear are outlined. (4) Conclusion: Given the complexities of inner ear injury, novel therapeutics such as extracellular vesicles could provide a means to modulate inflammation, stress pathways and apoptosis in the inner ear.
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Affiliation(s)
- Athanasia Warnecke
- Department of Otolaryngology, Hannover Medical School, 30625 Hannover, Germany
- Cluster of Excellence of the German Research Foundation (DFG; “Deutsche Forschungsgemeinschaft”) “Hearing4all”, 30625 Hannover, Germany
- Correspondence:
| | - Hinrich Staecker
- Department of Otolaryngology Head and Neck Surgery, University of Kansas School of Medicine, Rainbow Blvd., Kansas City, KS 66160, USA
| | - Eva Rohde
- GMP Unit, Spinal Cord Injury & Tissue Regeneration Centre Salzburg (SCI-TReCS), Paracelsus Medical University, 5020 Salzburg, Austria
- Transfer Centre for Extracellular Vesicle Theralytic Technologies (EV-TT), 5020 Salzburg, Austria
- Department of Transfusion Medicine, University Hospital, Salzburger Landeskliniken GesmbH (SALK) Paracelsus Medical University, 5020 Salzburg, Austria
| | - Mario Gimona
- GMP Unit, Spinal Cord Injury & Tissue Regeneration Centre Salzburg (SCI-TReCS), Paracelsus Medical University, 5020 Salzburg, Austria
- Transfer Centre for Extracellular Vesicle Theralytic Technologies (EV-TT), 5020 Salzburg, Austria
- Research Program “Nanovesicular Therapies”, Paracelsus Medical University, 5020 Salzburg, Austria
| | - Anja Giesemann
- Department of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
| | - Agnieszka J. Szczepek
- Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
- Faculty of Medicine and Health Sciences, University of Zielona Gora, 65-046 Zielona Gora, Poland
| | - Arianna Di Stadio
- Department GF Ingrassia, University of Catania, 95124 Catania, Italy
| | | | - Thomas Lenarz
- Department of Otolaryngology, Hannover Medical School, 30625 Hannover, Germany
- Cluster of Excellence of the German Research Foundation (DFG; “Deutsche Forschungsgemeinschaft”) “Hearing4all”, 30625 Hannover, Germany
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Li DF, Yang MF, Xu J, Xu HM, Zhu MZ, Liang YJ, Zhang Y, Tian CM, Nie YQ, Shi RY, Wang LS, Yao J. Extracellular Vesicles: The Next Generation Theranostic Nanomedicine for Inflammatory Bowel Disease. Int J Nanomedicine 2022; 17:3893-3911. [PMID: 36092245 PMCID: PMC9462519 DOI: 10.2147/ijn.s370784] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 08/25/2022] [Indexed: 12/02/2022] Open
Abstract
The recent rapid development in the field of extracellular vesicles (EVs) based nanotechnology has provided unprecedented opportunities for nanomedicine platforms. As natural nanocarriers, EVs such as exosomes, exosome-like nanoparticles and outer membrane vesicles (OMVs), have unique structure/composition/morphology characteristics, and show excellent physical and chemical/biochemical properties, making them a new generation of theranostic nanomedicine. Here, we reviewed the characteristics of EVs from the perspective of their formation and biological function in inflammatory bowel disease (IBD). Moreover, EVs can crucially participate in the interaction and communication of intestinal epithelial cells (IECs)-immune cells-gut microbiota to regulate immune response, intestinal inflammation and intestinal homeostasis. Interestingly, based on current representative examples in the field of exosomes and exosome-like nanoparticles for IBD treatment, it is shown that plant, milk, and cells-derived exosomes and exosome-like nanoparticles can exert a therapeutic effect through their components, such as proteins, nucleic acid, and lipids. Moreover, several drug loading methods and target modification of exosomes are used to improve their therapeutic capability. We also discussed the application of exosomes and exosome-like nanoparticles in the treatment of IBD. In this review, we aim to better and more clearly clarify the underlying mechanisms of the EVs in the pathogenesis of IBD, and provide directions of exosomes and exosome-like nanoparticles mediated for IBD treatment.
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Affiliation(s)
- De-feng Li
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China
| | - Mei-feng Yang
- Department of Hematology, Yantian District People’s Hospital, Shenzhen, People’s Republic of China
| | - Jing Xu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital (School of Medicine of South China University of Technology), Guangzhou, People’s Republic of China
| | - Hao-ming Xu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital (School of Medicine of South China University of Technology), Guangzhou, People’s Republic of China
| | - Min-zheng Zhu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital (School of Medicine of South China University of Technology), Guangzhou, People’s Republic of China
| | - Yu-jie Liang
- Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen, People’s Republic of China
| | - Yuan Zhang
- Department of Medical Administration, Huizhou Institute of Occupational Diseases Control and Prevention, Huizhou, People’s Republic of China
| | - Cheng-mei Tian
- Department of Emergency, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China
| | - Yu-qiang Nie
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital (School of Medicine of South China University of Technology), Guangzhou, People’s Republic of China
| | - Rui-yue Shi
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China
| | - Li-sheng Wang
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China
| | - Jun Yao
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China
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Rezabakhsh A, Mahdipour M, Nourazarian A, Habibollahi P, Sokullu E, Avci ÇB, Rahbarghazi R. Application of exosomes for the alleviation of COVID-19-related pathologies. Cell Biochem Funct 2022; 40:430-438. [PMID: 35647674 PMCID: PMC9348296 DOI: 10.1002/cbf.3720] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 05/09/2022] [Accepted: 05/19/2022] [Indexed: 12/17/2022]
Abstract
The pandemic of COVID-19 caused worldwide concern. Due to the lack of appropriate medications and the inefficiency of commercially available vaccines, lots of efforts are being made to develop de novo therapeutic modalities. Besides this, the possibility of several genetic mutations in the viral genome has led to the generation of resistant strains such as Omicron against neutralizing antibodies and vaccines, leading to worsening public health status. Exosomes (Exo), nanosized vesicles, possess several therapeutic properties that participate in intercellular communication. The discovery and application of Exo in regenerative medicine have paved the way for the alleviation of several pathologies. These nanosized particles act as natural bioshuttles and transfer several biomolecules and anti-inflammatory cytokines. To date, several approaches are available for the administration of Exo into the targeted site inside the body, although the establishment of standard administration routes remains unclear. As severe acute respiratory syndrome coronavirus 2 primarily affects the respiratory system, we here tried to highlight the transplantation of Exo in the alleviation of COVID-19 pathologies.
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Affiliation(s)
- Aysa Rezabakhsh
- Cardiovascular Research CenterTabriz University of Medical SciencesTabrizIran
| | - Mahdi Mahdipour
- Stem Cell Research CenterTabriz University of Medical SciencesTabrizIran
| | - Alireza Nourazarian
- Department of Basic Medical SciencesKhoy University of Medical SciencesKhoyIran
| | - Paria Habibollahi
- Department of Pharmacology and Toxicology, Faculty of PharmacyTabriz University of Medical SciencesTabrizIran
| | - Emel Sokullu
- Koç University Research Center for Translational Medicine (KUTTAM)IstanbulSariyerTurkey
| | - Çigir Biray Avci
- Department of Medical Biology, Faculty of MedicineEge UniversityIzmirTurkey
| | - Reza Rahbarghazi
- Stem Cell Research CenterTabriz University of Medical SciencesTabrizIran
- Department of Applied Cell Sciences, Faculty of Advanced Medical SciencesTabriz University of Medical SciencesTabrizIran
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Riveros ME, Ávila A, Schruers K, Ezquer F. Antioxidant Biomolecules and Their Potential for the Treatment of Difficult-to-Treat Depression and Conventional Treatment-Resistant Depression. Antioxidants (Basel) 2022; 11:540. [PMID: 35326190 PMCID: PMC8944633 DOI: 10.3390/antiox11030540] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 03/09/2022] [Accepted: 03/10/2022] [Indexed: 11/23/2022] Open
Abstract
Major depression is a devastating disease affecting an increasing number of people from a young age worldwide, a situation that is expected to be worsened by the COVID-19 pandemic. New approaches for the treatment of this disease are urgently needed since available treatments are not effective for all patients, take a long time to produce an effect, and are not well-tolerated in many cases; moreover, they are not safe for all patients. There is solid evidence showing that the antioxidant capacity is lower and the oxidative damage is higher in the brains of depressed patients as compared with healthy controls. Mitochondrial disfunction is associated with depression and other neuropsychiatric disorders, and this dysfunction can be an important source of oxidative damage. Additionally, neuroinflammation that is commonly present in the brain of depressive patients highly contributes to the generation of reactive oxygen species (ROS). There is evidence showing that pro-inflammatory diets can increase depression risk; on the contrary, an anti-inflammatory diet such as the Mediterranean diet can decrease it. Therefore, it is interesting to evaluate the possible role of plant-derived antioxidants in depression treatment and prevention as well as other biomolecules with high antioxidant and anti-inflammatory potential such as the molecules paracrinely secreted by mesenchymal stem cells. In this review, we evaluated the preclinical and clinical evidence showing the potential effects of different antioxidant and anti-inflammatory biomolecules as antidepressants, with a focus on difficult-to-treat depression and conventional treatment-resistant depression.
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Affiliation(s)
- María Eugenia Riveros
- Centro de Fisiología Celular e Integrativa, Facultad de Medicina Clínica Alemana-Universidad del Desarrollo, Santiago 7710162, Chile
| | - Alba Ávila
- Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana-Universidad del Desarrollo, Santiago 7710162, Chile;
| | - Koen Schruers
- Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, 6229 Maastricht, The Netherlands;
| | - Fernando Ezquer
- Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana-Universidad del Desarrollo, Santiago 7710162, Chile;
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