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Du Z, Feng L, Zhang Y, Peng X, Zhang S, Zhao R, Lei J, Li X, Yu G, Ding C. Route of Application and Dose Evaluation of Dental Pulp Stem Cells for the Treatment of Sialadenitis Caused by Sjögren's Syndrome: A Preclinical Study. Biomedicines 2025; 13:1068. [PMID: 40426896 DOI: 10.3390/biomedicines13051068] [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: 03/26/2025] [Revised: 04/22/2025] [Accepted: 04/24/2025] [Indexed: 05/29/2025] Open
Abstract
Background: Sjögren's syndrome (SS) is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations. In this study, non-obese diabetic (NOD) mice were used as an animal model for studying SS, to evaluate the optimal administration route and dose range of dental pulp stem cells (DPSCs) in the treatment of sialadenitis caused by SS. Methods: Different doses of DPSCs were transplanted into the submandibular glands (SMGs) of 14-week-old NOD mice through two different methods: injection or retrograde perfusion through the catheter orifice into the SMG. At 21 weeks of age, the saliva flow rate (SFR), ectopic lymphocytes, and CD4+ T-cell infiltration were measured. Tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) in the glandular tissues were also quantitatively detected. Results: Compared with untreated and PBS-injected controls, different-dose groups of the two administration methods showed an increased saliva flow rate of NOD mice to varying degrees, reduced infiltration of lymphocytes and CD4+ T cells in the SMG, and decreased IFN-γ/TNF-α levels. Finally, we compared these two administration routes and found that the perfusion of 2 × 105 DPSCs presents good therapeutic effects. Conclusions: DPSC perfusion through the catheter orifice is a simple and effective treatment method, which is worthy of further investigation through clinical trials.
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Affiliation(s)
- Zhihao Du
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, China
- Center Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, China
| | - Lifang Feng
- Department of Prosthodontics, North China University of Science and Technology, Stomatology, Tangshan Bay Ecological Zone No. 21 Bohai Avenue, Tangshan 063210, China
| | - Yu Zhang
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, China
| | - Xin Peng
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, China
| | - Shan Zhang
- Center Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, China
| | - Rui Zhao
- Center Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, China
| | - Jia Lei
- Center Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, China
| | - Xiaotong Li
- Center Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, China
| | - Guangyan Yu
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, China
| | - Chong Ding
- Center Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, China
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Zhang X, Liu T, Ma Z, Li G, Ding N, Wang Z, Guan Y, Zhang Y, Liu L, Chen X. VEGF secreted by human dental pulp stem cell promotes spinal cord injury repair by inhibiting microglial pyroptosis through the PI3K/AKT pathway. J Transl Med 2025; 23:437. [PMID: 40221710 PMCID: PMC11992863 DOI: 10.1186/s12967-025-06388-4] [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: 01/08/2025] [Accepted: 03/15/2025] [Indexed: 04/14/2025] Open
Abstract
BACKGROUND Spinal cord injury (SCI) remains a devastating central nervous system disorder. The complex pathological microenvironment following SCI, particularly the imbalance in neuroinflammation, contributes to its therapeutic challenges. Microglial pyroptosis, a type of programmed cell death, is pivotal in exacerbating neuroinflammation and secondary tissue damage after SCI. Our previous study demonstrated the inhibitory efficacy of conditioned medium (CM) derived from human dental pulp stem cells (DPSCs) on the microglial pyroptosis and its positive effects on the functional recovery in SCI models. However, the major secretory product in CM responsible for inhibiting microglial pyroptosis remains unclear. OBJECTIVE We aim to investigate whether vascular endothelial growth factor (VEGF) secreted by human DPSCs can alleviate microglial pyroptosis through the PI3K/AKT signaling pathway and promote motor and electrophysiological function recovery in SCI mice. METHODS Human DPSCs were isolated and cultured, and CM was collected for VEGF detection and further treatment. The BV2 cell line was established as a microglial pyroptosis model through the administration of lipopolysaccharide (LPS). SCI was induced in mice. Molecular and histological techniques were employed to evaluate pyroptosis and explore the underlying mechanisms both in vivo and vitro. RESULTS Human DPSC-derived VEGF significantly inhibited microglial pyroptosis both in vitro and vivo, as evidenced by the decreased expression of pyroptosis-related markers, such as caspase-1 and IL-1β. The anti-pyroptotic effects of VEGF were closely associated with the activation of the PI3K/AKT signaling pathway, which was identified as a key regulatory mechanism. Importantly, treatment with DPSC-CM improved the recovery of motor function and electrophysiological conduction in SCI mice. CONCLUSION Human DPSC-derived VEGF alleviates microglial pyroptosis via the PI3K/AKT signaling pathway, thereby contributing to the repair of SCI. Our study provides new insights into the potential for therapy of DPSCs and their secreted factors, particularly VEGF, offering new perspectives on the treatment of SCI.
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Affiliation(s)
- Xinwei Zhang
- Department of Orthopedics Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, China
| | - Tao Liu
- Department of Orthopedics Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, China
| | - Ziqian Ma
- Department of Orthopedics Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, China
| | - Guanghao Li
- Department of Orthopedics Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, China
| | - Nan Ding
- Department of Stomatology, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, China
| | - Zihang Wang
- Clinical Medical College, Fujian Medical University, Fujian, 350108, China
| | - Yun Guan
- Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
- Department of Neurological Surgery, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Yan Zhang
- Department of Orthopedics Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, China.
| | - Liang Liu
- Department of Orthopedics Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, China.
| | - Xueming Chen
- Department of Orthopedics Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, China.
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Chen YN, Chen YR, Yang BH, Lee PH, Kuo LT, Li CH. Intranasal administration of tissue inhibitor of metalloproteinase 1 extracted from stem cells from human exfoliated deciduous teeth-conditioned medium improves neurological outcomes and alpha-synuclein elimination in Parkinson's disease mice. J Dent Sci 2025; 20:1043-1051. [PMID: 40224104 PMCID: PMC11993047 DOI: 10.1016/j.jds.2024.11.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 11/26/2024] [Indexed: 04/15/2025] Open
Abstract
Background/purpose Parkinson's disease (PD) remains a challenging neurodegenerative disorder, requiring the exploration of innovative therapeutic strategies. This study assessed the neuroprotective effects of stem cells from human exfoliated deciduous teeth-conditioned medium (SHED-CM) in a rotenone-induced mouse model of PD. Materials and methods The SHED-CM, fractionated and purified via Fast Protein Liquid Chromatography (FPLC) into "yPD01", was administered intranasally to evaluate its impact on motor deficits, olfactory functions, and protein expressions in affected brain regions. Results Upon intranasal delivery, yPD01 produced significant improvements to motor deficits and restoration of protein expressions associated with PD pathology, particularly in the olfactory bulb and substantial nigra. Intriguingly, the intranasal route exhibited efficacy akin to intravenous administration, highlighting its potential as a minimally invasive yet equally effective therapeutic approach. Further investigation indicated key components within yPD01, denoted as peaks P1 and P5, showcasing pivotal therapeutic effects. These components were linked to the interruption of alpha-synuclein aggregation and its clearance within specific brain cells affected by PD. Conclusion Intranasally administered yPD01 shows neuroprotective potential for mitigating neurodegenerative symptoms, particularly in PD. The results provide valuable insights into potential mechanisms underlying the neuroprotective effects of SHED-CM and their implications for future therapeutic interventions in PD and related conditions.
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Affiliation(s)
- Yi-No Chen
- Non-invasive Cancer Therapy Research Institute - Taiwan, Taipei, Taiwan
- Division of Neurosurgery, Department of Surgery, MacKay Memorial Hospital, Taipei, Taiwan
| | - Yong-Ren Chen
- Non-invasive Cancer Therapy Research Institute - Taiwan, Taipei, Taiwan
- Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Bing-Heng Yang
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
- Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan
- Trace Element Research Center, Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan
| | - Po-Hui Lee
- Non-invasive Cancer Therapy Research Institute - Taiwan, Taipei, Taiwan
| | - Lu-Ting Kuo
- Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Chung-Hsing Li
- School of Dentistry and Graduate Institute of Dental Science, National Defense Medical Center, Taipei, Taiwan
- Division of Orthodontics and Pediatric Dentistry, Department of Dentistry, Tri-Service General Hospital, Taipei, Taiwan
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Kanamaru H, Suzuki H. Therapeutic potential of stem cells in subarachnoid hemorrhage. Neural Regen Res 2025; 20:936-945. [PMID: 38989928 PMCID: PMC11438332 DOI: 10.4103/nrr.nrr-d-24-00124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Accepted: 04/27/2024] [Indexed: 07/12/2024] Open
Abstract
Aneurysm rupture can result in subarachnoid hemorrhage, a condition with potentially severe consequences, such as disability and death. In the acute stage, early brain injury manifests as intracranial pressure elevation, global cerebral ischemia, acute hydrocephalus, and direct blood-brain contact due to aneurysm rupture. This may subsequently cause delayed cerebral infarction, often with cerebral vasospasm, significantly affecting patient outcomes. Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes. Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments. Stem cell therapy, with its multipotent differentiation capacity and anti-inflammatory effects, has emerged as a promising approach for treating previously deemed incurable conditions. This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.
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Affiliation(s)
- Hideki Kanamaru
- Department of Neurosurgery, Mie University Graduate School of Medicine, Tsu, Japan
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Wang W, Wang Y, Gao L. Stem Cells Treatment for Subarachnoid Hemorrhage. Neurologist 2025; 30:80-86. [PMID: 39450602 DOI: 10.1097/nrl.0000000000000589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2024]
Abstract
BACKGROUND Subarachnoid hemorrhage (SAH) refers to bleeding in the subarachnoid space, which is a serious neurologic emergency. However, the treatment effects of SAH are limited. In recent years, stem cell (SC) therapy has gradually become a very promising therapeutic method and advanced scientific research area for SAH. REVIEW SUMMARY The SCs used for SAH treatment are mainly bone marrow mesenchymal stem cells (BMSCs), umbilical cord mesenchymal stem cells (hUC-MSCs), dental pulp stem cells (DPSCs), neural stem cells (NSCs)/neural progenitor cell (NPC), and endothelial progenitor cell (EPC). The mechanisms mainly included differentiation and migration of SCs for tissue repair; alleviating neuronal apoptosis; anti-inflammatory effects; and blood-brain barrier (BBB) protection. The dosage of SCs was generally 10 6 orders of magnitude. The administration methods included intravenous injection, nasal, occipital foramen magnum, and intraventricular administration. The administration time is generally 1 hour after SAH modeling, but it may be as late as 24 hours or 6 days. Existing studies have confirmed the neuroprotective effect of SCs in the treatment of SAH. CONCLUSIONS SC has great potential application value in SAH treatment, a few case reports have provided support for this. However, the relevant research is still insufficient and there is still a lack of clinical research on the SC treatment for SAH to further evaluate the effectiveness and safety before it can go from experiment to clinical application.
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Affiliation(s)
| | | | - Liansheng Gao
- Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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He P, Zhang H, Wang J, Guo Y, Tian Q, Liu C, Gong P, Ye Q, Peng Y, Li M. Dental Pulp Stem Cells Attenuate Early Brain Injury After Subarachnoid Hemorrhage via miR-26a-5p/PTEN/AKT Pathway. Neurochem Res 2025; 50:91. [PMID: 39883266 DOI: 10.1007/s11064-025-04340-y] [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: 12/04/2024] [Revised: 01/06/2025] [Accepted: 01/13/2025] [Indexed: 01/31/2025]
Abstract
Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke with high morbidity, mortality and disability, and early brain injury (EBI) after SAH is crucial for prognosis. Recently, stem cell therapy has garnered significant attention in the treatment of neurological diseases. Compared to other stem cells, dental pulp stem cells (DPSCs) possess several advantages, including abundant sources, absence of ethical concerns, non-invasive procurement, non-tumorigenic history and neuroprotective potential. Therefore, we aim to investigate whether DPSCs can improve EBI after SAH, and explore the mechanisms. In our study, we utilized the endovascular perforation method to establish a SAH mouse model and investigated whether DPSCs administered via tail vein injection could improve EBI after SAH. Furthermore, we used hemin-stimulated HT22 cells to simulate neuronal cell injury induced by SAH and employed a co-culture approach to examine the effects of DPSCs on these cells. To gain insights into the potential mechanisms underlying the improvement of SAH-induced EBI by DPSCs, we conducted bioinformatics analysis. Finally, we further validated our findings through experiments. In vivo experiments, we found that DPSCs administration improved neurological dysfunction, reduced brain edema, and prevented neuronal apoptosis in SAH mice. Additionally, we observed a decrease in the expression level of miR-26a-5p in the cortical tissues of SAH mice, which was significantly increased following intravenous injection of DPSCs. Through bioinformatic analysis and luciferase reporter assay, we confirmed the target relationship between miR-26a-5p and PTEN. Moreover, we demonstrated that DPSCs exerted neuroprotective effects by modulating the miR-26a-5p/PTEN/AKT pathway. Our study demonstrates that DPSCs can improve EBI after SAH through the miR-26a-5p/PTEN/AKT pathway, laying a foundation for the application of DPSCs in SAH treatment. These findings provide a theoretical basis for further investigating the therapeutic mechanisms of DPSCs and developing novel treatment strategies in SAH.
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Affiliation(s)
- Peibang He
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
| | - Hui Zhang
- Center of Regenerative Medicine & Department of Stomatology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
| | - Jianfeng Wang
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
| | - Yujia Guo
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
| | - Qi Tian
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
| | - Chengli Liu
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
| | - Pian Gong
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
| | - Qingsong Ye
- Center of Regenerative Medicine & Department of Stomatology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
| | - Youjian Peng
- Center of Regenerative Medicine & Department of Stomatology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
| | - Mingchang Li
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
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Rostami M, Farahani P, Esmaelian S, Bahman Z, Fadel Hussein A, A Alrikabi H, Hosseini Hooshiar M, Yasamineh S. The Role of Dental-derived Stem Cell-based Therapy and Their Derived Extracellular Vesicles in Post-COVID-19 Syndrome-induced Tissue Damage. Stem Cell Rev Rep 2024; 20:2062-2103. [PMID: 39150646 DOI: 10.1007/s12015-024-10770-y] [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] [Accepted: 08/02/2024] [Indexed: 08/17/2024]
Abstract
Long coronavirus disease 2019 (COVID-19) is linked to an increased risk of post-acute sequelae affecting the pulmonary and extrapulmonary organ systems. Up to 20% of COVID-19 patients may proceed to a more serious form, such as severe pneumonia, acute respiratory distress syndrome (ARDS), or pulmonary fibrosis. Still, the majority of patients may only have mild, self-limiting sickness. Of particular concern is the possibility of parenchymal fibrosis and lung dysfunction in long-term COVID-19 patients. Furthermore, it has been observed that up to 43% of individuals hospitalized with COVID-19 also had acute renal injury (AKI). Care for kidney, brain, lung, cardiovascular, liver, ocular, and tissue injuries should be included in post-acute COVID-19 treatment. As a powerful immunomodulatory tool in regenerative medicine, dental stem cells (DSCs) have drawn much interest. Numerous immune cells and cytokines are involved in the excessive inflammatory response, which also has a significant effect on tissue regeneration. A unique reservoir of stem cells (SCs) for treating acute lung injury (ALI), liver damage, neurological diseases, cardiovascular issues, and renal damage may be found in tooth tissue, according to much research. Moreover, a growing corpus of in vivo research is connecting DSC-derived extracellular vesicles (DSC-EVs), which are essential paracrine effectors, to the beneficial effects of DSCs. DSC-EVs, which contain bioactive components and therapeutic potential in certain disorders, have been shown as potentially effective therapies for tissue damage after COVID-19. Consequently, we explore the properties of DSCs in this work. Next, we'll look at how SARS-CoV-2 affects tissue damage. Lastly, we have looked at the use of DSCs and DSC-EVs in managing COVID-19 and chronic tissue damage, such as injury to the heart, brain, lung, and other tissues.
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Affiliation(s)
- Mitra Rostami
- School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
| | - Pouria Farahani
- Doctor of Dental Surgery, Faculty of Dentistry, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Samar Esmaelian
- Faculty of Dentistry, Islamic Azad University, Tehran Branch, Tehran, Iran
| | - Zahra Bahman
- Faculty of dentistry, Belarusian state medical university, Minsk, Belarus
| | | | - Hareth A Alrikabi
- Collage of Dentist, National University of Science and Technology, Dhi Qar, 64001, Iraq
| | | | - Saman Yasamineh
- Young Researchers and Elite Club, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
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Chen YR, Wong CC, Chen YN, Yang BH, Lee PH, Shiau CY, Wang KC, Li CH. Factors derived from human exfoliated deciduous teeth stem cells reverse neurological deficits in a zebrafish model of Parkinson's disease. J Dent Sci 2024; 19:2035-2044. [PMID: 39347052 PMCID: PMC11437270 DOI: 10.1016/j.jds.2024.06.004] [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: 05/08/2024] [Revised: 06/03/2024] [Indexed: 10/01/2024] Open
Abstract
Background/purpose Mesenchymal stem cells exhibit therapeutic efficacy for brain injury. This study examined the effect of mesenchymal stem cells derived from human exfoliated deciduous teeth (SHED) on alleviating symptoms of Parkinson's disease (PD). Materials and methods SHED were isolated to examine the biosafety and bioavailability of stem cells derived from human exfoliated deciduous teeth-derived conditioned medium (SHED-CM) for the alleviation of PD symptoms in a 6-hydroxydopamine (6-OHDA)-induced PD zebrafish model. Results SHED-CM administration did not induce neurological, skin or muscle toxicity in control zebrafish at any dose, and estrogen equivalent testing showed no chronic toxicants. Induction of PD with 6-OHDA suppressed zebra SHED-CM was administered to zebrafish treated with 6-OHDA to induce PD symptoms. Similar to nomifensine, a drug with proven anti-PD potential, SHED-CM repaired the motor deficiencies in the zebrafish PD model. Conclusion Our results indicate the biosafety of SHED-CM and its therapeutic potential in treating PD in a zebrafish model.
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Affiliation(s)
- Yong-Ren Chen
- Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
- Non-invasive Cancer Therapy Research Institute - Taiwan, Taipei, Taiwan
| | - Chin-Chean Wong
- Non-invasive Cancer Therapy Research Institute - Taiwan, Taipei, Taiwan
- Department of Orthopedics, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan
- Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yi-No Chen
- Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of Neurosurgery, Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan
| | - Bing-Heng Yang
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
- Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan
- Trace Element Research Center, Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan
| | - Po-Hui Lee
- Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chia-Yang Shiau
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Kuo-Chuan Wang
- Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Chung-Hsing Li
- School of Dentistry and Graduate Institute of Dental Science, National Defense Medical Center, Taipei, Taiwan
- Division of Orthodontics and Pediatric Dentistry, Department of Dentistry, Tri-Service General Hospital, Taipei, Taiwan
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Rahnama Sisakht A, Tavasouli Z, Negahi A, Hosseini SA, Satarzadeh M. Dental pulp stem cells regenerate neural tissue in degenerative disorders and stroke rehabilitation: A scope systematic review. Heliyon 2024; 10:e35080. [PMID: 39166055 PMCID: PMC11334686 DOI: 10.1016/j.heliyon.2024.e35080] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 07/12/2024] [Accepted: 07/22/2024] [Indexed: 08/22/2024] Open
Abstract
Background Dental Pulp Stem Cells (DPSCs) possess a remarkable ability for tissue differentiation, making them highly efficient in tissue regeneration and inflammation regulation. This systematic study proposes to find an answer to the question, "Do DPSCs have the ability to regenerate and rehabilitate nerve tissue?" Methods This systematic review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, and the principle of non-bias was respected. All the articles from 2014 to 2024 were extracted from the Web of Science, PubMed, and Scopus databases. This study extracted the antigens and pro-inflammatory factors associated with DPSCs' involvement and how they affect the CNS's neural tissue regeneration. Results Two persons of researchers searched the database. After screening the full texts, they included 11 articles in their study. DPSCs control the following antigens: CD73, CD34, CD90, CD105, CD14, CD45, CD19Oct-4, CD73, CD31, CD34CD29CD44. Even though hematopoietic markers did not change much, OCT-4 and CD-73 were increased by DPSCs. DPSC-derived exosomes suppressed the expression of IL-6, IL-1β, TNF-α, and TGF, key mediators of nerve tissue inflammation. Additionally, DPSCs show high Vascular Endothelial Growth Factor (VEGF) expression in mice brain tissue cultures. DPSCs reduce Subarachnoid Hemorrhage (SAH), a condition in which blood collects in the subarachnoid space and causes ischemia. Discussion DPSCs showed the ability to regenerate nerve tissue and brain ganglia, stimulating angiogenesis by expressing cell markers and controlling growth factors in mice, and high therapeutic potential in neurodegenerative disorders. The present study invites further research in neurological disorders, specifically strokes, to prescribe these stem cells to the human population.
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Affiliation(s)
| | - Zahra Tavasouli
- Ghaemieh Health Care Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Ahmad Negahi
- School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
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Miao Y, Liang X, Chen J, Liu H, He Z, Qin Y, Liu A, Zhang R. Transfer of miR-877-3p via extracellular vesicles derived from dental pulp stem cells attenuates neuronal apoptosis and facilitates early neurological functional recovery after cerebral ischemia-reperfusion injury through the Bclaf1/P53 signaling pathway. Pharmacol Res 2024; 206:107266. [PMID: 38878918 DOI: 10.1016/j.phrs.2024.107266] [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: 02/21/2024] [Revised: 06/12/2024] [Accepted: 06/13/2024] [Indexed: 07/24/2024]
Abstract
Cerebral ischemia-reperfusion injury (I/RI) is one of the principal pathogenic factors in the poor prognosis of ischemic stroke, for which current therapeutic options to enhance neurological recovery are notably insufficient. Dental pulp stem cell-derived extracellular vesicles (DPSC-EVs) have promising prospects in stroke treatment and the specific underlying mechanisms have yet to be fully elucidated. The present study observed that DPSC-EVs ameliorated the degree of cerebral edema and infarct volume by reducing the apoptosis of neurons. Furthermore, the miRNA sequencing and functional enrichment analysis identified that miR-877-3p as a key component in DPSC-EVs, contributing to neuroprotection and anti-apoptotic effects. Following target prediction and dual-luciferase assay indicated that miR-877-3p interacted with Bcl-2-associated transcription factor (Bclaf1) to play a function. The miR-877-3p inhibitor or Bclaf1 overexpression reversed the neuroprotective effects of DPSC-EVs. The findings reveal a novel therapeutic pathway where miR-877-3p, transferred via DPSC-EVs, confers neuroprotection against cerebral I/RI, highlighting its potential in promoting neuronal survival and recovery post-ischemia.
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Affiliation(s)
- Yan Miao
- Department of Neurology, The Third Xiangya Hospital, Central South University, 410013, China
| | - Xin Liang
- Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, 100038, China
| | - Jigang Chen
- Department of burn and plastic surgery, Beijing Children's Hospital, Capital Medical University, 100045, China
| | - Hongyi Liu
- Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, 100070, China; School of Biomedical Engineering, Capital Medical University, Beijing 100069, China
| | - Zilong He
- Department of Neurosurgery, The Third Xiangya Hospital, Central South University, 410013, China
| | - Yongkai Qin
- Department of Neurosurgery, The Third Xiangya Hospital, Central South University, 410013, China
| | - Aihua Liu
- Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, 100070, China; Department of Neurosurgery, The Third Xiangya Hospital, Central South University, 410013, China.
| | - Ruxu Zhang
- Department of Neurology, The Third Xiangya Hospital, Central South University, 410013, China.
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Liang X, Miao Y, Tong X, Chen J, Liu H, He Z, Liu A, Hu Z. Dental pulp mesenchymal stem cell-derived exosomes inhibit neuroinflammation and microglial pyroptosis in subarachnoid hemorrhage via the miRNA-197-3p/FOXO3 axis. J Nanobiotechnology 2024; 22:426. [PMID: 39030593 PMCID: PMC11264715 DOI: 10.1186/s12951-024-02708-w] [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: 01/19/2024] [Accepted: 07/05/2024] [Indexed: 07/21/2024] Open
Abstract
BACKGROUND Subarachnoid hemorrhage (SAH) is a severe stroke subtype that lacks effective treatment. Exosomes derived from human dental pulp stem cells (DPSCs) are a promising acellular therapeutic strategy for neurological diseases. However, the therapeutic effects of DPSC-derived exosomes (DPSC-Exos) on SAH remain unknown. In this study, we investigated the therapeutic effects and mechanisms of action of DPSC-Exos in SAH. MATERIALS AND METHODS SAH was established using 120 male Sprague-Dawley rats. One hour after SAH induction, DPSC-Exos were administered via tail vein injection. To investigate the effect of DPSC-Exos, SAH grading, short-term and long-term neurobehavioral assessments, brain water content, western blot (WB), immunofluorescence staining, Nissl staining, and HE staining were performed. The role of miR-197-3p/FOXO3 in regulating pyroptosis was demonstrated through miRNA sequencing, bioinformatics analysis, and rescue experiments. The SAH model in vitro was established by stimulating BV2 cells with hemoglobin (Hb) and the underlying mechanism of DPSC-Exos was investigated through WB and Hoechst/PI staining. RESULTS The expressions of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were increased after SAH. DPSC-Exos alleviated brain edema and neuroinflammation by inhibiting the expression of FOXO3 and reducing NLRP3 inflammasome activation, leading to improved neurobehavioral functions at 24 h after SAH. In vitro, the expression of the NLRP3 inflammasome components (NLRP3 and caspase1-p20), GSDMD-N, and IL-18 was inhibited in BV2 cells pretreated with DPSC-Exos. Importantly, DPSC-Exos overexpressing miR-197-3p had a more obvious protective effect than those from NC-transfected DPSCs, while those from DPSCs transfected with the miR-197-3p inhibitor had a weaker protective effect. Functional studies indicated that miR-197-3p bound to the 3'-untranslated region of FOXO3, inhibiting its transcription. Furthermore, the overexpression of FOXO3 reversed the protective effects of miR-197-3p. CONCLUSIONS DPSC-Exos inhibited activation of the NLRP3 inflammasome and related cytokine release via the miR-197-3p/FOXO3 pathway, alleviated neuroinflammation, and inhibited microglial pyroptosis. These findings suggest that using DPSC-Exos is a promising therapeutic strategy for SAH.
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Affiliation(s)
- Xin Liang
- Department of Neurosurgery, Affiliated Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- Department of Neurosurgery, Affiliated Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Yan Miao
- Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Xin Tong
- Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China
- Cerebrovascular Disease Department, Neurological Disease Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Jigang Chen
- Department of burn and plastic surgery, Beijing Children's Hospital, Capital Medical University, Beijing, 100045, China
| | - Hongyi Liu
- Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China
- School of Biomedical Engineering, Capital Medical University, Beijing, 100069, China
| | - Zilong He
- Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Aihua Liu
- Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
- Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
- Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
- China National Clinical Research Centre for Neurological Diseases, Beijing, 100070, China.
| | - Zhiqiang Hu
- Department of Neurosurgery, Affiliated Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
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12
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Hardin LT, Abid N, Vang D, Han X, Thor D, Ojcius DM, Xiao N. miRNAs mediate the impact of smoking on dental pulp stem cells via the p53 pathway. Toxicol Sci 2024; 200:47-56. [PMID: 38636493 DOI: 10.1093/toxsci/kfae042] [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] [Indexed: 04/20/2024] Open
Abstract
Cigarette smoke changes the genomic and epigenomic imprint of cells. In this study, we investigated the biological consequences of extended cigarette smoke exposure on dental pulp stem cells (DPSCs) and the potential roles of miRNAs. DPSCs were treated with various doses of cigarette smoke condensate (CSC) for up to 6 weeks. Cell proliferation, survival, migration, and differentiation were evaluated. Cytokine and miRNA expression were profiled. The results showed that extended exposure to CSC significantly impaired the regenerative capacity of the DPSCs. Bioinformatic analysis showed that the cell cycle pathway, cancer pathways (small cell lung cancer, pancreatic, colorectal, and prostate cancer), and pathways for TNF, TGF-β, p53, PI3K-Akt, mTOR, and ErbB signal transduction, were associated with altered miRNA profiles. In particular, 3 miRNAs has-miR-26a-5p, has-miR-26b-5p, and has-miR-29b-3p fine-tune the p53 and cell cycle signaling pathways to regulate DPSC cellular activities. The work indicated that miRNAs are promising targets to modulate stem cell regeneration and understanding miRNA-targeted genes and their associated pathways in smoking individuals have significant implications for disease control and prevention.
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Affiliation(s)
- Leyla Tahrani Hardin
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, California 94103, USA
| | - Nabil Abid
- Department of Molecular and Cellular Biology, High Institute of Biotechnology of Monastir, University of Monastir, Monastir, 5000, Tunisia
- Laboratory of Transmissible Diseases and Biological Active Substances LR99ES27, Faculty of Pharmacy of Monastir, University of Monastir, Monastir, 5000, Tunisia
| | - David Vang
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, California 94103, USA
| | - Xiaoyuan Han
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, California 94103, USA
| | - Der Thor
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, California 94103, USA
| | - David M Ojcius
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, California 94103, USA
| | - Nan Xiao
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, California 94103, USA
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Yang LY, Tang SC, Lee JE, Chen YR, Chen YT, Chen KW, Hsieh ST, Wang KC. Recombinant soluble form of receptor for advanced glycation end products ameliorates microcirculation impairment and neuroinflammation after subarachnoid hemorrhage. Neurotherapeutics 2024; 21:e00312. [PMID: 38177024 DOI: 10.1016/j.neurot.2023.e00312] [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: 11/30/2023] [Revised: 12/12/2023] [Accepted: 12/15/2023] [Indexed: 01/06/2024] Open
Abstract
Impaired cerebral microcirculation after subarachnoid hemorrhage (SAH) has been shown to be related to delayed ischemic neurological deficits (DIND). We previously demonstrated the involvement of the receptor for advanced glycation end products (RAGE) in the pathogenesis of SAH related neuronal death. In the present study, we aimed to investigate the therapeutic effects of a recombinant soluble form of RAGE (sRAGE) on microcirculation impairment following SAH. Intrathecal injection of autologous blood in rats, mixed primary astrocyte and microglia cultures exposed to hemolysates and endothelial cells (ECs) from human brain microvascular exposed to glia-conditioned medium or SAH patient's CSF were used as experimental SAH models in vivo and in vitro. The results indicated that intrathecal administration of recombinant sRAGE significantly ameliorated the vasoconstriction of cortical arterioles and associated perfusion impairment, brain edema, reduced cell death, endothelial dysfunction, and improved motor performance at 24 and 48 h after SAH induction in rats. The in vitro results further showed that recombinant sRAGE significantly reduced astrocyte swelling and microglia activation, in parallel with decreased mRNA expression levels of pro-inflammatory cytokines including interleukin-6 (IL-6) and interleukin-1β (IL-1β) in vitro. Moreover, the in vitro model of SAH-induced p-eNOS and eNOS suppression, along with stress fiber formation in brain microvascular ECs, was effectively reversed by sRAGE treatment and led to a decrease in cleaved-caspase 3 expression. In summary, recombinant sRAGE effectively lessened microcirculation impairment and vascular injury after SAH via the mechanism of anti-inflammation, which may provide a potential therapeutic strategy for SAH.
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Affiliation(s)
- Ling-Yu Yang
- Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Sung-Chun Tang
- Department of Neurology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jing-Er Lee
- Department of Neurology, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan
| | - Yong-Ren Chen
- Non-invasive Cancer Therapy Research Institute, Taipei, Taiwan; Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital Jin-Shan Branch, New Taipei City, Taiwan
| | - Yi-Tzu Chen
- Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Kuo-Wei Chen
- Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Sung-Tsang Hsieh
- Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Kuo-Chuan Wang
- Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
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Younes R, Issa Y, Jdaa N, Chouaib B, Brugioti V, Challuau D, Raoul C, Scamps F, Cuisinier F, Hilaire C. The Secretome of Human Dental Pulp Stem Cells and Its Components GDF15 and HB-EGF Protect Amyotrophic Lateral Sclerosis Motoneurons against Death. Biomedicines 2023; 11:2152. [PMID: 37626649 PMCID: PMC10452672 DOI: 10.3390/biomedicines11082152] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 07/27/2023] [Accepted: 07/28/2023] [Indexed: 08/27/2023] Open
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal and incurable paralytic disorder caused by the progressive death of upper and lower motoneurons. Although numerous strategies have been developed to slow disease progression and improve life quality, to date only a few therapeutic treatments are available with still unsatisfactory therapeutic benefits. The secretome of dental pulp stem cells (DPSCs) contains numerous neurotrophic factors that could promote motoneuron survival. Accordingly, DPSCs confer neuroprotective benefits to the SOD1G93A mouse model of ALS. However, the mode of action of DPSC secretome on motoneurons remains largely unknown. Here, we used conditioned medium of human DPSCs (DPSCs-CM) and assessed its effect on survival, axonal length, and electrical activity of cultured wildtype and SOD1G93A motoneurons. To further understand the role of individual factors secreted by DPSCs and to circumvent the secretome variability bias, we focused on GDF15 and HB-EGF whose neuroprotective properties remain elusive in the ALS pathogenic context. DPSCs-CM rescues motoneurons from trophic factor deprivation-induced death, promotes axon outgrowth of wildtype but not SOD1G93A mutant motoneurons, and has no impact on the spontaneous electrical activity of wildtype or mutant motoneurons. Both GDF15 and HB-EGF protect SOD1G93A motoneurons against nitric oxide-induced death, but not against death induced by trophic factor deprivation. GDF15 and HB-EGF receptors were found to be expressed in the spinal cord, with a two-fold increase in expression for the GDF15 low-affinity receptor in SOD1G93A mice. Therefore, the secretome of DPSCs appears as a new potential therapeutic candidate for ALS.
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Affiliation(s)
- Richard Younes
- INM, University of Montpellier, INSERM, 34295 Montpellier, France
- LBN, University of Montpellier, 34193 Montpellier, France
- Neuroscience Research Center, Faculty of Medical Sciences, Lebanese University, Beirut 6573, Lebanon
| | - Youssef Issa
- INM, University of Montpellier, INSERM, 34295 Montpellier, France
| | - Nadia Jdaa
- INM, University of Montpellier, INSERM, 34295 Montpellier, France
| | - Batoul Chouaib
- LBN, University of Montpellier, 34193 Montpellier, France
- Human Health Department, IRSN, SERAMED, LRMed, 92262 Fontenay-aux-Roses, France
| | | | - Désiré Challuau
- INM, University of Montpellier, INSERM, 34295 Montpellier, France
| | - Cédric Raoul
- INM, University of Montpellier, INSERM, 34295 Montpellier, France
| | | | | | - Cécile Hilaire
- INM, University of Montpellier, INSERM, 34295 Montpellier, France
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15
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Wu XB, Wu YT, Guo XX, Xiang C, Chen PS, Qin W, Shi ZS. Circular RNA hsa_circ_0007990 as a blood biomarker for unruptured intracranial aneurysm with aneurysm wall enhancement. Front Immunol 2022; 13:1061592. [PMID: 36466848 PMCID: PMC9714537 DOI: 10.3389/fimmu.2022.1061592] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 11/04/2022] [Indexed: 10/17/2023] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) may involve the formation and rupture of intracranial aneurysms (IA). Inflammation plays a vital role in the development and progression of IA, which can be reflected by aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI). This study aims to evaluate the role of circRNAs as the blood inflammatory biomarker for unruptured IA (UIA) patients with AWE on HR-VWI. METHODS We analyzed the circRNA expression profiles in the peripheral blood samples among subjects from saccular UIA with AWE, UIA without AWE, and healthy controls by the circRNA microarray. The differential expression of hsa_circ_0007990 was assessed. We constructed the hsa_circ_0007990-microRNA-mRNA network and the regulatory axis of hub genes associated with the AWE in UIA. RESULTS Eighteen patients harboring saccular UIAs with HR VWI and five healthy controls were included. We found 412 differentially expressed circRNAs between UIA patients and healthy controls by circRNA microarray. Two hundred thirty-one circRNAs were significantly differentially expressed in UIA patients with AWE compared with those without AWE. Twelve upregulated circRNAs were associated with AWE of UIA, including hsa_circ_0007990, hsa_circ_0114507, hsa_circ_0020460, hsa_circ_0053944, hsa_circ_0000758, hsa_circ_0000034, hsa_circ_0009127, hsa_circ_0052793, hsa_circ_0000301 and hsa_circ_0000729. The expression of hsa_circ_0007990 was increased gradually in the healthy control, UIA without AWE, and UIA with AWE confirmed by RT-PCR (P<0.001). We predicted 4 RNA binding proteins (Ago2, DGCR8, EIF4A3, PTB) and period circadian regulator 1 as an encoding protein with hsa_circ_0007990. The hsa_circ_0007990-microRNA-mRNA network containing five microRNAs (miR-4717-5p, miR-1275, miR-150-3p, miR-18a-5p, miR-18b-5p), and 97 mRNAs was constructed. The five hub genes (hypoxia-inducible factor 1 subunit alpha, estrogen receptor 1, forkhead box O1, insulin-like growth factor 1, CREB binding protein) were involved in the inflammatory response. CONCLUSION Differentially expressed blood circRNAs associated with AWE on HR-VWI may be the novel inflammatory biomarkers for assessing UIA patients. The mechanism of hsa_circRNA_0007990 for UIA progression needs to investigate further.
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Affiliation(s)
- Xiao-Bing Wu
- Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - You-Tao Wu
- Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xin-Xing Guo
- Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Chun Xiang
- Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Pei-Sheng Chen
- Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wang Qin
- Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhong-Song Shi
- Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Province Key Laboratory of Brain Function and Disease, Sun Yat-sen University, Guangzhou, China
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16
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Ogata K, Moriyama M, Matsumura-Kawashima M, Kawado T, Yano A, Nakamura S. The Therapeutic Potential of Secreted Factors from Dental Pulp Stem Cells for Various Diseases. Biomedicines 2022; 10:biomedicines10051049. [PMID: 35625786 PMCID: PMC9138802 DOI: 10.3390/biomedicines10051049] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/18/2022] [Accepted: 04/27/2022] [Indexed: 11/16/2022] Open
Abstract
An alternative source of mesenchymal stem cells has recently been discovered: dental pulp stem cells (DPSCs), including deciduous teeth, which can thus comprise potential tools for regenerative medicine. DPSCs derive from the neural crest and are normally implicated in dentin homeostasis. The clinical application of mesenchymal stem cells (MSCs) involving DPSCs contains various limitations, such as high cost, low safety, and cell handling issues, as well as invasive sample collection procedures. Although MSCs implantation offers favorable outcomes on specific diseases, implanted MSCs cannot survive for a long period. It is thus considered that their mediated mechanism of action involves paracrine effects. It has been recently reported that secreted molecules in DPSCs-conditioned media (DPSC-CM) contain various trophic factors and cytokines and that DPSC-CM are effective in models of various diseases. In the current study, we focus on the characteristics of DPSC-CM and their therapeutic potential against various disorders.
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17
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Chouaib B, Cuisinier F, Collart-Dutilleul PY. Dental stem cell-conditioned medium for tissue regeneration: Optimization of production and storage. World J Stem Cells 2022; 14:287-302. [PMID: 35662860 PMCID: PMC9136565 DOI: 10.4252/wjsc.v14.i4.287] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 05/19/2021] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSC) effects on tissue regeneration are mainly mediated by their secreted substances (secretome), inducing their paracrine activity. This Conditioned medium (CM), including soluble factors (proteins, nucleic acids, lipids) and extracellular vesicles is emerging as a potential alternative to cell therapy. However, the manufacturing of CM suffers from variable procedures and protocols leading to varying results between studies. Besides, there is no well-defined optimized procedure targeting specific applications in regenerative medicine. AIM To focus on conditioned medium produced from dental MSC (DMSC-CM), we reviewed the current parameters and manufacturing protocols, in order to propose a standardization and optimization of these manufacturing procedures. METHODS We have selected all publications investigating the effects of dental MSC secretome in in vitro and in vivo models of tissue regeneration, in accordance with the PRISMA guidelines. RESULTS A total of 351 results were identified. And based on the inclusion criteria described above, 118 unique articles were included in the systematic review. DMSC-CM production was considered at three stages: before CM recovery (cell sources for CM), during CM production (culture conditions) and after production (CM treatment). CONCLUSION No clear consensus could be recovered as evidence-based methods, but we were able to describe the most commonly used protocols: donors under 30 years of age, dental pulp stem cells and exfoliated deciduous tooth stem cells with cell passage between 1 and 5, at a confluence of 70% to 80%. CM were often collected during 48 h, and stored at -80 °C. It is important to point out that the preconditioning environment had a significant impact on DMSC-CM content and efficiency.
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Affiliation(s)
- Batoul Chouaib
- Laboratory Bioengineering and Nanosciences UR_UM104, University of Montpellier, Montpellier 34000, France
| | - Frédéric Cuisinier
- Laboratory Bioengineering and Nanosciences UR_UM104, University of Montpellier, Montpellier 34000, France
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18
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Gugliandolo A, Mazzon E. Dental Mesenchymal Stem Cell Secretome: An Intriguing Approach for Neuroprotection and Neuroregeneration. Int J Mol Sci 2021; 23:ijms23010456. [PMID: 35008878 PMCID: PMC8745761 DOI: 10.3390/ijms23010456] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 12/28/2021] [Accepted: 12/28/2021] [Indexed: 12/12/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are known for their beneficial effects and regenerative potential. In particular, dental-derived MSCs have the advantage of easier accessibility and a non-invasive isolation method. Moreover, thanks to their neural crest origin, dental MSCs seem to have a more prominent neuroregenerative potential. Indeed, in basal conditions they also express neuronal markers. However, it is now well known that the beneficial actions of MSCs depend, at least in part, on their secretome, referring to all the bioactive molecules released in the conditioned medium (CM) or in extracellular vesicles (EVs). In this review we focus on the applications of the secretome derived from dental MSCs for neuroregeneration and neuroprotection. The secretomes of different dental MSCs have been tested for their effects for neuroregenerative purposes, and the secretomes of dental pulp stem cells and stem cells from human exfoliated deciduous teeth are the most studied. Both the CM and EVs obtained from dental MSCs showed that they are able to promote neurite outgrowth and neuroprotective effects. Interestingly, dental-derived MSC secretome showed stronger neuroregenerative and neuroprotective effects compared to that obtained from other MSC sources. For these reasons, the secretome obtained from dental MSCs may represent a promising approach for neuroprotective treatments.
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Zhu S, Ying Y, Wu Q, Ni Z, Huang Z, Cai P, Tu Y, Ying W, Ye J, Zhang R, Zhang Y, Chen M, Xiang Z, Dou H, Huang Q, Li X, He H, Xiao J, Ye Q, Wang Z. Alginate self-adhesive hydrogel combined with dental pulp stem cells and FGF21 repairs hemisection spinal cord injury via apoptosis and autophagy mechanisms. CHEMICAL ENGINEERING JOURNAL 2021; 426:130827. [DOI: 10.1016/j.cej.2021.130827] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Cui Y, Bai M, Guo D, Yang Y, Chen H, Sun J, Xie J, Zhou X. Insulin-like growth factor 1 promotes neural differentiation of human stem cells from the apical papilla. Arch Oral Biol 2021; 131:105264. [PMID: 34598025 DOI: 10.1016/j.archoralbio.2021.105264] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 09/09/2021] [Accepted: 09/11/2021] [Indexed: 02/05/2023]
Abstract
OBJECTIVE Insulin-like growth factor 1 (IGF1) is one of the vital factors in regenerative endodontics. Previous studies have focused on the role of IGF1 in the mineralization of dental tissues. However, the role of IGF1 in the neural differentiation of dental stem cells was little discussed. DESIGN IGF1 was overexpressed in human stem cells from the apical papilla (hSCAPs) by lentivirus and knocked down in hSCAPs by small interfering RNA. The neural differentiation level of hSCAPs was investigated histologically by HE staining and Nissl staining after neural induction for 3 days. The expression of proteins was examined by western blot and immunofluorescence. RESULTS IGF1 promoted neural differentiation of hSCAPs, more cell processes and Nissl-positive body stained cells. IGF1 overexpression could both promote glial differentiation in hSCAPs, characterized by the increase of S100β and GFAP proteins, and neuronal differentiation, characterized by the increase of βIII-tubulin and functional GAD67/vGLUT1 proteins. Conversely, IGF1 knockdown suppressed both glial and neuronal differentiation. IGF1 activated AKT to regulate the early neural differentiation of hSCAPs. CONCLUSIONS The results indicate IGF1 could promote neural differentiation of hSCAPs by activating AKT signaling and provide a cue for the candidate of induced neural seeding cells in regenerative endodontics.
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Affiliation(s)
- Yujia Cui
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China; Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Mingru Bai
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China; Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Daimo Guo
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China; Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Yueyi Yang
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China; Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Haoran Chen
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China; Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Jianxun Sun
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China; Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Jing Xie
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
| | - Xuedong Zhou
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China; Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
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21
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Yan Z, Wu Q, Cai W, Xiang H, Wen L, Zhang A, Peng Y, Zhang X, Wang H. Identifying critical genes associated with aneurysmal subarachnoid hemorrhage by weighted gene co-expression network analysis. Aging (Albany NY) 2021; 13:22345-22360. [PMID: 34542421 PMCID: PMC8507255 DOI: 10.18632/aging.203542] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 08/11/2021] [Indexed: 12/13/2022]
Abstract
Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening medical condition with a high mortality and disability rate. aSAH has an unclear pathogenesis, and limited treatment options are available. Here, we aimed to identify critical genes involved in aSAH pathogenesis using peripheral blood gene expression data of 43 patients with aSAH due to ruptured intracranial aneurysms and 18 controls with headache, downloaded from Gene Expression Omnibus. These data were used to construct a co-expression network using weighted gene co-expression network analysis (WGCNA). The biological functions of the hub genes were explored, and critical genes were selected by combining with differentially expressed genes analysis. Fourteen modules were identified by WGCNA. Among those modules, red, blue, brown and cyan modules were closely associated with aSAH. Moreover, 364 hub genes in the significant modules were found to play important roles in aSAH. Biological function analysis suggested that protein biosynthesis-related processes and inflammatory responses-related processes were involved in the pathology of aSAH pathology. Combined with differentially expressed genes analysis and validation in 35 clinical samples, seven gene (CD27, ANXA3, ACSL1, PGLYRP1, ALPL, ARG1, and TPST1) were identified as potential biomarkers for aSAH, and three genes (ANXA3, ALPL, and ARG1) were changed with disease development, that may provide new insights into potential molecular mechanisms for aSAH.
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Affiliation(s)
- Zhizhong Yan
- The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.,Department of Neurosurgery, Jinling Hospital, Nanjing 210002, China.,Department of Neurosurgery, The 904th Hospital of The Joint Logistics Support Force of Chinese People's Liberation Army, Wuxi 214000, China
| | - Qi Wu
- Department of Neurosurgery, Jinling Hospital, Nanjing 210002, China
| | - Wei Cai
- Department of Neurosurgery, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, China
| | - Haitao Xiang
- Department of Neurosurgery, Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou 215028, China
| | - Lili Wen
- Department of Neurosurgery, Jinling Hospital, Nanjing 210002, China
| | - An Zhang
- Department of Neurosurgery, Jinling Hospital, Nanjing 210002, China
| | - Yaonan Peng
- Department of Neurosurgery, Jinling Hospital, Nanjing 210002, China
| | - Xin Zhang
- Department of Neurosurgery, Jinling Hospital, Nanjing 210002, China
| | - Handong Wang
- The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.,Department of Neurosurgery, Jinling Hospital, Nanjing 210002, China
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22
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Peterson C, Umoye AO, Puglisi CH, Waldau B. Mechanisms of memory impairment in animal models of nontraumatic intracranial hemorrhage: A systematic review of the literature. BRAIN HEMORRHAGES 2021; 3:77-93. [DOI: 10.1016/j.hest.2021.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
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23
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Mukai T, Sei K, Nagamura-Inoue T. Mesenchymal Stromal Cells Perspective: New Potential Therapeutic for the Treatment of Neurological Diseases. Pharmaceutics 2021; 13:pharmaceutics13081159. [PMID: 34452120 PMCID: PMC8401282 DOI: 10.3390/pharmaceutics13081159] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 07/23/2021] [Accepted: 07/24/2021] [Indexed: 12/13/2022] Open
Abstract
Several studies have shown that mesenchymal stromal/stem cells (MSCs) exert their neuroprotective and neurorestorative efficacy via the secretion of neurotrophic factors. Based on these studies, many clinical trials using MSCs for the treatment of neurological disorders have been conducted, and results regarding their feasibility and efficacy have been reported. The present review aims to highlight the characteristics and basic research regarding the role of MSCs in neurological disease and to discuss the recent progress in clinical trials using MSCs to treat various neurological disorders.
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Affiliation(s)
- Takeo Mukai
- Department of Pediatrics, The University of Tokyo Hospital, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
- Department of Cell Processing and Transfusion, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; (K.S.); (T.N.-I.)
- Correspondence: ; Tel.: +81-3-3815-5411; Fax: 81-3-5449-5452
| | - Kenshi Sei
- Department of Cell Processing and Transfusion, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; (K.S.); (T.N.-I.)
| | - Tokiko Nagamura-Inoue
- Department of Cell Processing and Transfusion, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; (K.S.); (T.N.-I.)
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24
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Gong YH, Hao SL, Wang BC. Mesenchymal Stem Cells Transplantation in Intracerebral Hemorrhage: Application and Challenges. Front Cell Neurosci 2021; 15:653367. [PMID: 33841103 PMCID: PMC8024645 DOI: 10.3389/fncel.2021.653367] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 03/01/2021] [Indexed: 01/01/2023] Open
Abstract
Intracerebral hemorrhage (ICH) is one of the leading causes of death and long-term disability worldwide. Mesenchymal stem cell (MSC) therapies have demonstrated improved outcomes for treating ICH-induced neuronal defects, and the neural network reconstruction and neurological function recovery were enhanced in rodent ICH models through the mechanisms of neurogenesis, angiogenesis, anti-inflammation, and anti-apoptosis. However, many key issues associated with the survival, differentiation, and safety of grafted MSCs after ICH remain to be resolved, which hinder the clinical translation of MSC therapy. Herein, we reviewed an overview of the research status of MSC transplantation after ICH in different species including rodents, swine, monkey, and human, and the challenges for MSC-mediated ICH recovery from pathological microenvironment have been summarized. Furthermore, some efficient strategies for the outcome improvement of MSC transplantation were proposed.
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Affiliation(s)
- Yu-Hua Gong
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China
| | - Shi-Lei Hao
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China
| | - Bo-Chu Wang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China
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25
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Dental Pulp Stem Cells on Implant Surface: An In Vitro Study. BIOMED RESEARCH INTERNATIONAL 2021; 2021:3582342. [PMID: 33834063 PMCID: PMC8012148 DOI: 10.1155/2021/3582342] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 10/28/2020] [Accepted: 03/14/2021] [Indexed: 02/06/2023]
Abstract
In the field of biology and medicine, one hears often about stem cells and their potential. The dental implant new surfaces, subjected to specific treatments, perform better and allow for quicker healing times and better clinical performance. The purpose of this study is to evaluate from a biological point of view the interaction and cytotoxicity between stem cells derived from dental pulp (DPSCs) and titanium surfaces. Through the creation of complex cells/implant, this study is aimed at analyzing the cytotoxicity of dental implant surfaces (Myth (Maipek Manufacturer Industrial Care, Naples, Italy)) and the adhesion capacity of cells on them and at considering the essential factors for implant healing such as osteoinduction and vasculogenesis. These parameters are pointed out through histology (3D cell culture), immunofluorescence, proliferation assays, scanning electron microscopy, and PCR investigations. The results of the dental implant surface and its interaction with the DPSCs are encouraging, obtaining results increasing the mineralization of the tissues. The knowledge of this type of interaction, highlighting its chemical and biological features, is certainly also an excellent starting point for the development of even more performing surfaces for having better healing in the oral surgical procedures related to dental implant positioning.
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26
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Improvement of Impaired Motor Functions by Human Dental Exfoliated Deciduous Teeth Stem Cell-Derived Factors in a Rat Model of Parkinson's Disease. Int J Mol Sci 2020; 21:ijms21113807. [PMID: 32471263 PMCID: PMC7312764 DOI: 10.3390/ijms21113807] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 05/24/2020] [Accepted: 05/25/2020] [Indexed: 12/15/2022] Open
Abstract
Parkinson's disease (PD) is a long-term degenerative disease of the central nervous system (CNS) that primarily affects the motor system. So far there is no effective treatment for PD, only some drugs, surgery, and comprehensive treatment can alleviate the symptoms of PD. Stem cells derived from human exfoliated deciduous teeth (SHED), mesenchymal stem cells derived from dental pulp, may have promising potential in regenerative medicine. In this study, we examine the therapeutic effect of SHED-derived conditioned medium (SHED-CM) in a rotenone-induced PD rat model. Intravenous administration of SHED-CM generated by standardized procedures significantly improved the PD symptoms accompanied with increased tyrosine hydroxylase amounts in the striatum, and decreased α-synuclein levels in both the nigra and striatum, from rotenone-treated rats. In addition, this SHED-CM treatment decreased both Iba-1 and CD4 levels in these brain areas. Gene ontology analysis indicated that the biological process of genes affected by SHED-CM was primarily implicated in neurodevelopment and nerve regeneration. The major constituents of SHED-CM included insulin-like growth factor binding protein-6 (IGFBP-6), tissue inhibitor of metalloproteinase (TIMP)-2, TIMP-1, and transforming growth factor 1 (TGF-1). RNA-sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) revealed that these factors may ameliorate PD symptoms through modulating the cholinergic synapses, calcium signaling pathways, serotoninergic synapses, and axon guidance. In conclusion, our data indicate that SHED-CM contains active constituents that may have promising efficacy to alleviate PD.
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27
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He J, Zhang L, Yu Y, Luo X, Wei M, Chen G, Shen Y. Effects of clazosentan, cilostazol, and statins on aneurysmal subarachnoid hemorrhage: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e19902. [PMID: 32332668 PMCID: PMC7440251 DOI: 10.1097/md.0000000000019902] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Aneurysmal subarachnoid hemorrhage (aSAH) is a disease caused by the infiltration of blood into the subarachnoid space due to the rupture of an intracranial aneurysm. It is a serious cerebrovascular disease, with a mortality rate of about 40% worldwide, which seriously threatens human life and health. Many drugs are used to treat aSAH and its complications, and some have been tested in systematic reviews and have shown good effects. But which drug has the best effect remains unclear. This network meta-analysis (NMA) aims to assess the effectiveness and feasibility of clazosentan, cilostazol, and statins in patients with aSAH. METHODS We will search for EMBASE.com, PubMed, the Cochrane Library, and Web of Science from inception to December 2019. Randomized controlled trials (RCTs) reporting efficacy and safety of clazosentan, cilostazol, and statins compared with the control, or compared with each other for the treatment of aSAH will be included. Two independent reviewers will assess the risk of bias of the included RCTs with the Cochrane "Risk of bias" tool. The pairwise meta-analysis will be performed with the random-effects model. The NMA will be performed in a Bayesian hierarchical framework using Markov Chain Monte Carlo method in WinBUGS 1.4.3. Egger test and funnel plot will be used to assess the publication bias. We will evaluate the quality of evidence for each outcome according to the GRADE approach. RESULTS The results of this NMA will be submitted to a peer-reviewed journal for publication. CONCLUSION This study will summarize up-to-date evidence to compare the efficacy and safety of clazosentan, cilostazol, and statins on aSAH.PROSPERO registration number: CRD42019147523.
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Affiliation(s)
- Junfang He
- Department of Neurological Rehabilitation, Rehabilitation Center Hospital of Gansu Province
| | - Li Zhang
- The Third Ward of Cardiovascular Clinical Medical Center, Affiliated Hospital of Gansu University of Chinese Medicine
| | - Yao Yu
- Pathogens Biology Institute, School of Basic Medical Sciences of Lanzhou University
| | - Xinyue Luo
- The Second Clinical Medical College of Lanzhou University
| | - Min Wei
- Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou
| | - Gen Chen
- Pathogens Biology Institute, School of Basic Medical Sciences of Lanzhou University
- Basic Medical School, Guilin Medical University, Guilin
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28
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El Moshy S, Radwan IA, Rady D, Abbass MMS, El-Rashidy AA, Sadek KM, Dörfer CE, Fawzy El-Sayed KM. Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications. Stem Cells Int 2020; 2020:7593402. [PMID: 32089709 PMCID: PMC7013327 DOI: 10.1155/2020/7593402] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Revised: 12/23/2019] [Accepted: 01/10/2020] [Indexed: 12/13/2022] Open
Abstract
Regenerative medicine literature has proposed mesenchymal stem/progenitor cell- (MSC-) mediated therapeutic approaches for their great potential in managing various diseases and tissue defects. Dental MSCs represent promising alternatives to nondental MSCs, owing to their ease of harvesting with minimally invasive procedures. Their mechanism of action has been attributed to their cell-to-cell contacts as well as to the paracrine effect of their secreted factors, namely, secretome. In this context, dental MSC-derived secretome/conditioned medium could represent a unique cell-free regenerative and therapeutic approach, with fascinating advantages over parent cells. This article reviews the application of different populations of dental MSC secretome/conditioned medium in in vitro and in vivo animal models, highlights their significant implementation in treating different tissue' diseases, and clarifies the significant bioactive molecules involved in their regenerative potential. The analysis of these recent studies clearly indicate that dental MSCs' secretome/conditioned medium could be effective in treating neural injuries, for dental tissue regeneration, in repairing bone defects, and in managing cardiovascular diseases, diabetes mellitus, hepatic regeneration, and skin injuries, through regulating anti-inflammatory, antiapoptotic, angiogenic, osteogenic, and neurogenic mediators.
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Affiliation(s)
- Sara El Moshy
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Israa Ahmed Radwan
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Dina Rady
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Marwa M. S. Abbass
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Aiah A. El-Rashidy
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Biomaterials Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Khadiga M. Sadek
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Biomaterials Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Christof E. Dörfer
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
| | - Karim M. Fawzy El-Sayed
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
- Oral Medicine and Periodontology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
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