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Riza YM, Alzahrani FA. Rewiring the Spine-Cutting-Edge Stem Cell Therapies for Spinal Cord Repair. Int J Mol Sci 2025; 26:5048. [PMID: 40507858 PMCID: PMC12154377 DOI: 10.3390/ijms26115048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2025] [Revised: 05/11/2025] [Accepted: 05/21/2025] [Indexed: 06/16/2025] Open
Abstract
Spinal cord injury (SCI) is a debilitating neurological condition that leads to severe disabilities, significantly reducing patients' quality of life and imposing substantial societal and economic burdens. SCI involves a complex pathogenesis, including primary irreversible damage and secondary injury driven by neuroinflammation, apoptosis, and ischemia. Current treatments often provide limited efficacy, underscoring the urgent need for innovative therapeutic strategies. This paper aims to explore the potential use of stem cell (SC) therapy and exosome-based treatments as transformative approaches for managing SCI and mitigating associated disabilities. SCs, such as mesenchymal stem cells (MSCs), neural stem cells (NSCs), and embryonic stem cells (ESCs), demonstrate regenerative capabilities, including self-renewal, differentiation into neurons and glial cells, and modulation of the injury microenvironment. These properties enable SCs to reduce inflammation, inhibit apoptosis, and promote neuronal regeneration in preclinical models. Exosome-based therapies, derived from SCs, offer a novel alternative by addressing challenges like immune rejection and tumorigenicity. Exosomes deliver biomolecules, such as miRNAs, fostering anti-inflammatory, anti-apoptotic, and pro-regenerative effects. They have shown efficacy in improving motor function, reducing glial scarring, and enhancing axonal regrowth in SCI models. The objective of this paper is to provide a comprehensive review of SC therapy and exosome-based approaches, emphasizing their potential to revolutionize SCI management while addressing ethical concerns, immune rejection, and the need for large-scale clinical trials. These therapies hold promise for improving recovery outcomes and alleviating the profound disabilities associated with SCI.
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Affiliation(s)
- Yasir Mohamed Riza
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
- Department of Biochemistry, Faculty of Science, Embryonic Stem Cell Unit, King Fahad Center for Medical Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Faisal A. Alzahrani
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
- Department of Biochemistry, Faculty of Science, Embryonic Stem Cell Unit, King Fahad Center for Medical Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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2
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Daghrery A, Dal-Fabbro R, Xu J, Kaigler D, de Ruijter M, Gawlitta D, Malda J, Bottino MC. Niche-inspired collagen infused melt electrowritten scaffolds for craniofacial bone regeneration. BIOMATERIALS ADVANCES 2025; 170:214222. [PMID: 39923603 PMCID: PMC11893008 DOI: 10.1016/j.bioadv.2025.214222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 01/08/2025] [Accepted: 02/03/2025] [Indexed: 02/11/2025]
Abstract
Advances in tissue engineering are focused on devising improved therapeutics to reconstruct craniofacial bones. In cell-based strategies, biomaterials with specific physicochemical properties can mimic natural environments, supporting stem cell renewal, survivability, and cell fate. This study highlights the engineering of a 3D-printed (Melt Electrowritten, MEW) fluorinated‑calcium phosphate (F/CaP)-coated polymeric scaffold infused with collagen (COL) that boosts the performance of transplanted alveolar bone-derived mesenchymal stem cells (aBMSCs). Electron microscopy revealed micron-sized (2.7 μm) polymeric fibers forming a porous (500 μm fiber strand spacing) composite scaffold with a uniform F/CaP coating homogeneously infiltrated with collagen. In vitro, our findings underscored the cytocompatibility of the collagen-infused F/CaP-coated composite scaffold, fostering a suitable environment for aBMSCs proliferation and differentiation. Cells within the F/CaP-coated constructs exhibited upregulated osteogenic gene activity, and the addition of collagen augmented the expression of critical bone-forming genes (i.e., Runx2 and OCN). After in vivo implantation, the scaffolds integrated well with the surrounding host tissue, supporting extensive blood vessel infiltration. Notably, the collagen-infused F/CaP-coated composite scaffolds showed an increased CD31-positive vessel growth compared to the non-coated counterparts. At 8 weeks, aBMSCs-laden F/CaP-Coated+COL composite scaffolds exhibited robust bone formation, creating connecting bony bridges in calvarial defects. Importantly, F/CaP-Coated+COL composite scaffolds displayed pronounced OCN expression, indicating enhanced osteogenic potential. Thus, the engineered F/CaP-coated polymeric scaffold laden with aBMSCs and infused with collagen has proven effective in supporting cell growth, vascularization, and rapid bone regeneration, suggesting potential for future clinical use.
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Affiliation(s)
- Arwa Daghrery
- Department of Restorative Dental Sciences, School of Dentistry, Jazan University, Jazan, Saudi Arabia; Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, United States
| | - Renan Dal-Fabbro
- Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, United States
| | - Jinping Xu
- Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, United States
| | - Darnell Kaigler
- Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI, United States
| | - Mylène de Ruijter
- Regenerative Medicine Center Utrecht, Utrecht, the Netherlands; Department of Orthopedics, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands
| | - Debby Gawlitta
- Regenerative Medicine Center Utrecht, Utrecht, the Netherlands; Department of Oral and Maxillofacial Surgery & Special Dental Care (Division of Surgical Specialties), Utrecht University, Utrecht, the Netherlands
| | - Jos Malda
- Regenerative Medicine Center Utrecht, Utrecht, the Netherlands; Department of Orthopedics, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands
| | - Marco C Bottino
- Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, United States; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI, United States.
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Wang K, Liu X, Jiang X, Chen S, Wang H, Wang Z, Wang Q, Li Z. Human dental pulp stem cells for spinal cord injury. Stem Cell Res Ther 2025; 16:123. [PMID: 40055766 PMCID: PMC11887269 DOI: 10.1186/s13287-025-04244-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Accepted: 02/19/2025] [Indexed: 05/13/2025] Open
Abstract
Spinal cord injury (SCI) is a serious neurological disorder that causes loss of mobility, pain, and autonomic dysfunction, resulting in altered sensation and devastating loss of function. Current treatments for SCI mainly focus on surgery and drug therapy to promote neurological recovery. However, there are virtually no effective remedies for irreversible nerve damage that result in a victim's loss of motor function and sensory changes that occur after an injury. With the continuous development of medical technology, stem-cell-based regenerative medicine provides researchers with new treatment ideas. The effectiveness of mesenchymal stem cells and their derivatives from different sources in treating SCI varies. Recent studies have highlighted that dental pulp stem cells (DPSCs) may contribute to anti-inflammatory regulation, anti-apoptotic regulation, and axonal regeneration in the treatment of SCI patients. In addition, the combination of new biomaterials and dental pulp stem cells is promising in the treatment of SCI. This article reviews the role of DPSCs in SCI treatment in recent years, discusses the advantages of DPSCs, explores potential development directions, and looks forward to providing new insights for future research in this critical field.
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Affiliation(s)
- Kaizhong Wang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning Province, China
| | - Xiangyan Liu
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning Province, China
| | - Xukai Jiang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning Province, China
| | - Shuang Chen
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning Province, China
| | - Hui Wang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning Province, China
| | - Zhenbo Wang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning Province, China
| | - Qiwen Wang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning Province, China
| | - Zhonghai Li
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, China.
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning Province, China.
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning Province, China.
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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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Diez-Guardia V, Tian Y, Guo Y, Li J, Cui S, Dreiss CA, Gentleman E, Wang X. Controlled Release of Human Dental Pulp Stem Cell-Derived Exosomes from Hydrogels Attenuates Temporomandibular Joint Osteoarthritis. Adv Healthc Mater 2024:e2402923. [PMID: 39713912 DOI: 10.1002/adhm.202402923] [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: 08/06/2024] [Revised: 11/27/2024] [Indexed: 12/24/2024]
Abstract
Temporomandibular joint osteoarthritis (TMJOA) is a painful inflammatory condition that limits mouth opening. Cell-derived exosomes, which have anti-inflammatory effects, are emerging as a treatment for TMJOA. Injection of dental pulp stem cells (DPSCs), which secrete exosomes, can moderate tissue damage in a rat model of TMJOA. However, injected exosomes are quickly cleared, necessitating repeated injections for therapeutic efficacy. Here, vinyl sulfone-modified hyaluronic acid (HA-VS) hydrogels, suitable for encapsulating exosomes are formulated. HA-VS hydrogels degrade in the presence of hyaluronidase and allow for the release of beads of similar size to exosomes over 3 to 6 days. In a rat model of TMJOA, injection of exosomes or exosomes within HA-VS hydrogels significantly attenuated damage-mediated subchondral bone loss as determined by micro-computed tomography, and reduced inflammatory and tissue damage scores as assessed by histology. Overall, DPSCs-derived exosomes attenuated joint damage, but treatment with exosomes within HA-VS hydrogels shows additional protective effects on subchondral bone maintenance and integrity. These findings confirm the protective effects of DPSCs-derived exosomes in moderating tissue damage in TMJOA and suggest that combining exosomes with HA hydrogels can further promote their therapeutic effects.
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Affiliation(s)
- Victor Diez-Guardia
- Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK
| | - Yajing Tian
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China
- National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, 100081, China
- Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, China
- Center of Stomatology, China-Japan Friendship Hospital, Beijing, 100029, China
| | - Yunzhe Guo
- Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK
| | - Jiaying Li
- Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK
| | - Shengjie Cui
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China
- National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, 100081, China
- Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, China
| | - Cécile A Dreiss
- Institute of Pharmaceutical Science, King's College London, London, SE1 9NH, UK
| | - Eileen Gentleman
- Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK
- Department of Biomedical Sciences, University of Lausanne, Lausanne, 1005, Switzerland
| | - Xuedong Wang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China
- National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, 100081, China
- Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, China
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Naeimi A, Mousavi SF, Amini N, Golipoor M, Ghasemi Hamidabadi H. Therapeutic potential of melatonin-pretreated human dental pulp stem cells (hDPSCs) in an animal model of spinal cord injury. Sci Rep 2024; 14:28174. [PMID: 39548147 PMCID: PMC11568238 DOI: 10.1038/s41598-024-78077-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 10/28/2024] [Indexed: 11/17/2024] Open
Abstract
Dental pulp stem cells (DPSCs) show potential for treating neurodegenerative and traumatic diseases due to their neural crest origin. Melatonin (MT), an endogenous neurohormone with well-documented anti-inflammatory and antioxidant properties, has shown promising results with MSCs in terms of engraftment, proliferation, and neuronal differentiation in animal SCI models. However, the effects of melatonin preconditioning on human dental pulp stem cells (hDPSCs) for SCI treatment remain unclear. This study investigates the impact of melatonin preconditioning on hDPSCs engraftment, neural differentiation, and neurological function in rats with SCI. Forty-two male Sprague-Dawley rats were divided into six groups: Control, Sham, Model, Vehicle, Lesion Treatment A (SCI + hDPSCs), and Lesion Treatment B (SCI + MT-hDPSCs). After obtaining hDPSCs, stem cells were evaluated using flow cytometry. Cell viability was assessed using the MTT assay. SCI was induced in the Model, Vehicle, Lesion Treatment A, and Lesion Treatment B groups. The Lesion Treatment A and B groups received hDPSCs and hDPSCs pretreated with melatonin, respectively, 1 week after SCI, while the Vehicle group received only an intravenous injection of DMEM to simulate treatment. The other groups were used for behavioral testing. Immunohistochemistry (IHC) was employed to assess hDPSCs engraftment and differentiation at the SCI site. Motor function across the six groups was evaluated using the Basso, Beattie, and Bresnahan (BBB) score. Histological studies and cell counts confirmed hDPSCs implantation at the injury site, with a significantly higher presence in the MT-hDPSCs compared to hDPSCs (p < 0.01). IHC revealed that hDPSCs and MT-hDPSCs differentiated into neurons and astrocytes, with greater differentiation observed in the MT-hDPSCs compared to the hDPSCs (p < 0.01 and p < 0.05, respectively). Functional improvement was noted in both SCI + hDPSCs and SCI + MT-hDPSCs groups compared to SCI and Vehicle groups from Week 4 onward (p < 0.001). Significant differences were also observed between the SCI + hDPSCs and SCI + MT-hDPSCs groups starting from Week 7 (p < 0.01). Preconditioning hDPSCs with melatonin enhances engraftment, neuronal differentiation, and greater performance improvement compared to hDPSCs alone in the SCI animal model.
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Affiliation(s)
- Arvin Naeimi
- Student Research Committee, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Seyedeh Fatemeh Mousavi
- Student Research Committee, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Naser Amini
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mandana Golipoor
- Neuroscience Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
| | - Hatef Ghasemi Hamidabadi
- Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
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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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Shu Y, Otake M, Seta Y, Hori K, Kuramochi A, Ohba Y, Teramura Y. Activation of cellular antioxidative stress and migration activities by purified components from immortalized stem cells from human exfoliated deciduous teeth. Sci Rep 2024; 14:15340. [PMID: 38961142 PMCID: PMC11222459 DOI: 10.1038/s41598-024-66213-8] [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: 01/25/2024] [Accepted: 06/28/2024] [Indexed: 07/05/2024] Open
Abstract
Although stem cell-based regenerative medicine has been extensively studied, it remains difficult to reconstruct three dimensional tissues and organs in combination with vascular systems in vitro. One clinically successful therapy is transplantation of mesenchymal stem cells (MSC) into patients with graft versus host disease. However, transplanted cells are immediately damaged and destroyed because of innate immune reactions provoked by thrombogenic inflammation, and patients need to take immunosuppressive drugs for the immunological regulation of allogeneic cells. This reduces the benefits of stem cell transplantation. Therefore, alternative therapies are more realistic options for clinical use. In this study, we aimed to take advantage of the therapeutic efficacy of MSC and use multiple cytokines released from MSC, that is, stem cells from human exfoliated deciduous teeth (SHEDs). Here, we purified components from conditioned media of immortalized SHED (IM-SHED-CM) and evaluated the activities of intracellular dehydrogenase, cell migration, and antioxidative stress by studying the cells. The immortalization of SHED could make the stable supply of CM possible. We found that the fractionated component of 50-100 kD from IM-SHED-CM had higher efficacy than the original IM-SHED-CM in terms of intracellular dehydrogenase and cell migration in which intracellular signal transduction was activated via receptor tyrosine kinases, and the glutathione peroxidase and reductase system was highly active. Although antioxidative stress activities in the fractionated component of 50-100 kD had slightly lower than that of original IM-SHE-CM, the fraction still had the activity. Thus, the use of fractionated components of 50-100 kD from IM-SHED-CM could be an alternative choice for MSC transplantation because the purified components from CM could maintain the effect of cytokines from SHED.
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Affiliation(s)
- Yujing Shu
- U-Factor Co., Ltd, 1F, ESCALIER Rokubancho, 7-11, Rokubancho, Chiyoda, Tokyo, 102-0085, Japan
| | - Masato Otake
- U-Factor Co., Ltd, 1F, ESCALIER Rokubancho, 7-11, Rokubancho, Chiyoda, Tokyo, 102-0085, Japan
| | - Yasuhiro Seta
- Hitonowa Medical, K.PLAZA 2F, 1-7 Rokubancho, Chiyoda, Tokyo, 102-0085, Japan
| | - Keigo Hori
- U-Factor Co., Ltd, 1F, ESCALIER Rokubancho, 7-11, Rokubancho, Chiyoda, Tokyo, 102-0085, Japan
| | - Akiko Kuramochi
- Cellular and Molecular Biotechnology Research Institute (CMB), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan
| | - Yoshio Ohba
- Cellular and Molecular Biotechnology Research Institute (CMB), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan
| | - Yuji Teramura
- Cellular and Molecular Biotechnology Research Institute (CMB), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan.
- Department of Immunology, Genetics and Pathology (IGP), Uppsala University, Dag Hammarskjölds Väg 20, 751 85, Uppsala, Sweden.
- Master's/Doctoral Program in Life Science Innovation (T-LSI), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
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9
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Fu J, Li W, Mao T, Chen Z, Lai L, Lin J, Nie Z, Sun Y, Chen Y, Zhang Q, Li X. The potential therapeutic roles of dental pulp stem cells in spinal cord injury. Front Mol Biosci 2024; 11:1363838. [PMID: 38741719 PMCID: PMC11089131 DOI: 10.3389/fmolb.2024.1363838] [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: 12/31/2023] [Accepted: 03/04/2024] [Indexed: 05/16/2024] Open
Abstract
Spinal cord injury (SCI) can lead to serious functional disorders, which have serious impacts on patients and society. The current traditional treatments of SCI are not effective the injured spinal cord is difficult to repair and regenerate. In recent years, stem cell transplantation for the treatment of SCI has been a hot research topic. Dental pulp stem cells have strong abilities of self-renewal and multi-directional differentiation, and have been applied for tissue engineering and regenerative medicine. And dental pulp stem cells have certain advantages in neuro-regenetation, bringing new hope to biotherapy for SCI. This article reviews the characteristics of dental pulp stem cells and their research progress in the treatment of SCI.
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Affiliation(s)
- Jing Fu
- Department of Stomatology, Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
| | - Wenjie Li
- Department of Anesthesiology and Surgery, Qingdao Municipal Hospital Group, Qingdao, China
| | - Tengfei Mao
- Yuncheng Central Hospital Affiliated to Shanxi Medical University, Yuncheng, China
| | - Zaipeng Chen
- College of Pharmacy, Guizhou Medical University, Guiyang, China
| | - Lili Lai
- Department of Orthopedics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jiachen Lin
- Department of Orthopedics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Zhiqiang Nie
- College of Pharmacy, Guizhou Medical University, Guiyang, China
| | - Yunkai Sun
- The Eighth Clinical Medical College of Shanxi Medical University, Yuncheng, China
| | - Yanqin Chen
- College of Pharmacy, Guizhou Medical University, Guiyang, China
| | - Qin Zhang
- Yuncheng Central Hospital Affiliated to Shanxi Medical University, Yuncheng, China
| | - Xigong Li
- Department of Orthopedics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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10
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Guo X, Jiang C, Chen Z, Wang X, Hong F, Hao D. Regulation of the JAK/STAT signaling pathway in spinal cord injury: an updated review. Front Immunol 2023; 14:1276445. [PMID: 38022526 PMCID: PMC10663250 DOI: 10.3389/fimmu.2023.1276445] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Accepted: 10/11/2023] [Indexed: 12/01/2023] Open
Abstract
Cytokines are involved in neural homeostasis and pathological processes associated with neuroinflammation after spinal cord injury (SCI). The biological effect of cytokines, including those associated with acute or chronic SCI pathologies, are the result of receptor-mediated signaling through the Janus kinases (JAKs) as well as the signal transducers and activators of transcription (STAT) DNA-binding protein families. Although therapies targeting at cytokines have led to significant changes in the treatment of SCI, they present difficulties in various aspects for the direct use by patients themselves. Several small-molecule inhibitors of JAKs, which may affect multiple pro-inflammatory cytokine-dependent pathways, as well as STATs, are in clinical development for the treatment of SCI. This review describes the current understanding of the JAK-STAT signaling in neuroendocrine homeostasis and diseases, together with the rationale for targeting at this pathway for the treatment of SCI.
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Affiliation(s)
- Xinyu Guo
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi’an, China
| | - Chao Jiang
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi’an, China
| | - Zhe Chen
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi’an, China
| | - Xiaohui Wang
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi’an, China
- Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
| | - Fan Hong
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi’an, China
| | - Dingjun Hao
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi’an, China
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11
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Li Y, Wu M, Xing X, Li X, Shi C. Effect of Wnt10a/β-catenin signaling pathway on promoting the repair of different types of dentin-pulp injury. In Vitro Cell Dev Biol Anim 2023; 59:486-504. [PMID: 37700204 PMCID: PMC10520212 DOI: 10.1007/s11626-023-00785-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 07/06/2023] [Indexed: 09/14/2023]
Abstract
How to repair dentin-pulp injury effectively has always been a clinical problem, and the comparative study of repair process between different injuries is unknown. Dental pulp stem cells (DPSCs) often are selected as seed cells for the study of dentin-pulp injury repair due to excellent advantages in odontogenesis and pulp differentiation. Although many previous researches have indicated that the Wnt protein and Wnt/β-catenin signaling pathway were crucial for dental growth, development, and injury repair, the specific mechanism remained unknown. In this study, different dentine-pulp injury models of adult mice were established successfully by abrasion and cutting methods. The gross morphology and micro-CT were used to observe the repair of injured mice incisor in different groups. We found that the repair time of each group was different. The repair time of the cutting group was longer than the abrasion group and the qRT-PCR detection showed that the expression of DSPP in the cutting group was higher than that in the abrasion group, but there was no significant difference in proliferation among the groups. In vivo and cell experiments showed that activation of Wnt/β-catenin signaling pathway can promote the proliferation and odontoblast differentiation of DPSCs. In addition, by using RNAscope staining, we observed that Wnt10a was mainly expressed in the proliferative region and partially expressed in the odontoblast region. The Western blotting results showed that in the early stage of repair, the expression of Wnt10a increased with the extension of days after injury in both abrasion and cutting group and the increase of Wnt10a was tested obviously on the 5th day after injury. But on the 7th day after injury, the expression of Wnt10a was still obvious in the cutting group, while the expression of Wnt10a was significantly reduced in the abrasion group, which was close to the control group. It is suggested that Wnt10a acts as a repair-related protein and has an important role in tooth injury repair. Wnt10a was activated by R-spondin and LiCl, and Wnt10a-siRNA DPSCs were constructed to inhibit Wnt10a. The results showed that Wnt10a/β-catenin signaling pathway promoted the proliferation and odontoblast differentiation of DPSCs. It plays a crucial role in the repair process of different injuries. This study enriched the mechanisms of Wnt10a /β-catenin signaling pathways in different types of dentin-pulp injury repair, which could provide experimental evidences for the target gene screening and also give some new ideas for the subsequent research on the molecular mechanisms of tooth regeneration.
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Affiliation(s)
- Yue Li
- Department of Orthodontics, Kunming Medical University School and Hospital of Stomatology, Kunming, 650106, China
- Yunnan Key Laboratory of Stomatology, Kunming, 650106, China
| | - Meiying Wu
- Department of Orthodontics, Kunming Medical University School and Hospital of Stomatology, Kunming, 650106, China
- Yunnan Key Laboratory of Stomatology, Kunming, 650106, China
| | - Xinyu Xing
- Department of Orthodontics, Kunming Medical University School and Hospital of Stomatology, Kunming, 650106, China
- Yunnan Key Laboratory of Stomatology, Kunming, 650106, China
| | - Xingxing Li
- Yunnan Key Laboratory of Stomatology, Kunming, 650106, China
- Department of Prosthodontics, Kunming Medical University School and Hospital of Stomatology, Kunming, 650106, China
| | - Congchong Shi
- Department of Orthodontics, Kunming Medical University School and Hospital of Stomatology, Kunming, 650106, China.
- Yunnan Key Laboratory of Stomatology, Kunming, 650106, China.
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12
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Dwivedi S, Choudhary P, Gupta A, Singh S. Therapeutical growth in oligodendroglial fate induction via transdifferentiation of stem cells for neuroregenerative therapy. Biochimie 2023; 211:35-56. [PMID: 36842627 DOI: 10.1016/j.biochi.2023.02.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 12/20/2022] [Accepted: 02/21/2023] [Indexed: 02/27/2023]
Abstract
The merits of stem cell therapy and research are undisputed due to their widespread usage in the treatment of neurodegenerative diseases and demyelinating disorders. Cell replacement therapy especially revolves around stem cells and their induction into different cell lineages both adult and progenitor - belonging to each germ layer, prior to transplantation or disease modeling studies. The nervous system is abundant in glial cells and among these are oligodendrocytes capable of myelinating new-born neurons and remyelination of axons with lost or damaged myelin sheath. But demyelinating diseases generate tremendous deficit between myelin loss and recovery. To compensate for this loss, analyze the defects in remyelination mechanisms as well as to trigger full recovery in such patients mesenchymal stem cells (MSCs) have been induced to transdifferentiate into oligodendrocytes. But such experiments are riddled with problems like prolonged, tenuous and complicated protocols that stretch longer than the time taken for the spread of demyelination-associated after-effects. This review delves into such protocols and the combinations of different molecules and factors that have been recruited to derive bona fide oligodendrocytes from in vitro differentiation of embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and MSCs with special focus on MSC-derived oligodendrocytes.
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Affiliation(s)
- Shrey Dwivedi
- Department of Applied Sciences, Indian Institute of Information Technology, Allahabad, U.P., India
| | - Princy Choudhary
- Department of Applied Sciences, Indian Institute of Information Technology, Allahabad, U.P., India
| | - Ayushi Gupta
- Department of Applied Sciences, Indian Institute of Information Technology, Allahabad, U.P., India
| | - Sangeeta Singh
- Department of Applied Sciences, Indian Institute of Information Technology, Allahabad, U.P., India.
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13
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Sramkó B, Földes A, Kádár K, Varga G, Zsembery Á, Pircs K. The Wisdom in Teeth: Neuronal Differentiation of Dental Pulp Cells. Cell Reprogram 2023; 25:32-44. [PMID: 36719998 PMCID: PMC9963504 DOI: 10.1089/cell.2022.0102] [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] [Indexed: 02/02/2023] Open
Abstract
Mesenchymal stem/stromal cells (MSCs) are found in almost all postnatal organs. Under appropriate environmental cues, multipotency enables MSCs to serve as progenitors for several lineage-specific, differentiated cell types. In vitro expansion and differentiation of MSCs give the opportunity to obtain hardly available somatic cells, such as neurons. The neurogenic potential of MSCs makes them a promising, autologous source to restore damaged tissue and as such, they have received much attention in the field of regenerative medicine. Several stem cell pool candidates have been studied thus far, but only a few of them showed neurogenic differentiation potential. Due to their embryonic ontology, stem cells residing in the stroma of the dental pulp chamber are an exciting source for in vitro neural cell differentiation. In this study, we review the key properties of dental pulp stem cells (DPSCs), with a particular focus on their neurogenic potential. Moreover, we summarize the various presently available methods used for neural differentiation of human DPSCs also emphasizing the difficulties in reproducibly high production of such cells. We postulate that because DPSCs are stem cells with very close ontology to neurogenic lineages, they may serve as excellent targets for neuronal differentiation in vitro and even for direct reprogramming.
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Affiliation(s)
- Bendegúz Sramkó
- HCEMM-SU Neurobiology and Neurodegenerative Diseases Research Group, Budapest, Hungary.,Institute of Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Anna Földes
- Department of Oral Biology, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
| | - Kristóf Kádár
- Department of Oral Biology, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
| | - Gábor Varga
- Department of Oral Biology, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
| | - Ákos Zsembery
- Department of Oral Biology, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
| | - Karolina Pircs
- HCEMM-SU Neurobiology and Neurodegenerative Diseases Research Group, Budapest, Hungary.,Institute of Translational Medicine, Semmelweis University, Budapest, Hungary.,Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, Lund, Sweden
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14
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Mu X, Liu H, Yang S, Li Y, Xiang L, Hu M, Wang X. Chitosan Tubes Inoculated with Dental Pulp Stem Cells and Stem Cell Factor Enhance Facial Nerve-Vascularized Regeneration in Rabbits. ACS OMEGA 2022; 7:18509-18520. [PMID: 35694480 PMCID: PMC9178771 DOI: 10.1021/acsomega.2c01176] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 05/16/2022] [Indexed: 06/15/2023]
Abstract
Facial nerve injury is a common clinical condition that leads to disfigurement and emotional distress in the affected individuals, and the recovery presents clinical challenges. Tissue engineering is the standard method to repair nerve defects. However, nerve regeneration is still not satisfactory because of poor neovascularization after implantation, especially for the long-segment nerve defects. In the current study, we aimed to investigate the potential of chitosan tubes inoculated with stem cell factor (SCF) and dental pulp stem cells (DPSCs) in facial nerve-vascularized regeneration. In the in vitro experiment, DPSCs were isolated, cultured, and then identified. The optimal concentration of SCF was screened by CCK8. Cytoskeleton and living-cell staining, migration, CCK8 test, and neural differentiation assays were performed, revealing that SCF promoted the biological activity of DPSCs. Surprisingly, SCF increased the neural differentiation of DPSCs. The migration and angiogenesis experiments were carried out to show that SCF promoted the angiogenesis and migration of human umbilical vein endothelial cells (HUVECs). In the facial nerve, 7 mm defects of New Zealand white rabbits, hematoxylin-eosin (HE), immunohistochemistry, toluidine blue staining, and transmission electron microscopy observation were performed at 12 weeks postsurgery to show more nerve fibers and better myelin sheath in the SCF + DPSC group. In addition, the whisker movements, Masson's staining, and western blot assays were performed, demonstrating functional repair and that the expression level of CD31 protein in the group SCF + DPSCs was relatively close to that in the group Autograft. In summary, chitosan tubes inoculated with SCF and DPSCs increased neurovascularization and provided an effective method for repairing facial nerve defects, indicating great promise for clinical application.
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Affiliation(s)
- Xiaodan Mu
- Department
of Stomotology, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
| | - Huawei Liu
- Department
of Stomotology, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
| | - Shuhui Yang
- Department
of Materials Science and Engineering, State Key Laboratory of New
Ceramics and Fine Processing, Tsinghua University, Beijing 100084, China
| | - Yongfeng Li
- Department
of Stomotology, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
| | - Lei Xiang
- Department
of Stomotology, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
| | - Min Hu
- Department
of Stomotology, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
| | - Xiumei Wang
- Department
of Materials Science and Engineering, State Key Laboratory of New
Ceramics and Fine Processing, Tsinghua University, Beijing 100084, China
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15
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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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16
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Huang L, Zheng Z, Bai D, Han X. Stem Cells from Human Exfoliated Deciduous Teeth and their Promise as Preventive and Therapeutic Strategies for Neurological Diseases and Injuries. Curr Stem Cell Res Ther 2021; 17:527-536. [PMID: 34967291 DOI: 10.2174/1574888x17666211229155533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 10/04/2021] [Accepted: 11/15/2021] [Indexed: 11/22/2022]
Abstract
Stem cells from human exfoliated deciduous teeth (SHEDs) are relatively easy to isolate from exfoliated deciduous teeth, which are obtained via dental therapy as biological waste. SHEDs originate from the embryonic neural crest and therefore have considerable potential for neurogenic differentiation. Currently, an increasing amount of research attention is focused on the therapeutic applications of SHEDs in neurological diseases and injuries. In this article, we summarize the biological characteristics of SHEDs and the potential role of SHEDs and their derivatives, including conditioned medium from SHEDs and the exosomes they secrete, in the prevention and treatment of neurological diseases and injuries.
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Affiliation(s)
- Lingyi Huang
- West China College of Stomatology/ State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China
| | - Zizhuo Zheng
- West China College of Stomatology/ State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China
| | - Ding Bai
- West China College of Stomatology/ State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China
| | - Xianglong Han
- West China College of Stomatology/ State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China
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17
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Oki Y, Harano K, Hara Y, Sasajima Y, Sasaki R, Ito T, Fujishiro M, Ito T. Cationic surface charge effect on proliferation and protein production of human dental pulp stem cells cultured on diethylaminoethyl-modified cellulose porous beads. Biochem Eng J 2021. [DOI: 10.1016/j.bej.2021.108217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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18
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Ouchi T, Nakagawa T. Tissue Regeneration and Physiological Functional Recovery in Dental and Craniofacial Fields. Biomolecules 2021; 11:1644. [PMID: 34827642 PMCID: PMC8615394 DOI: 10.3390/biom11111644] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 11/04/2021] [Indexed: 02/07/2023] Open
Abstract
Dental and oral tissues maintain homeostasis through potential reparative or regenerative processes [...].
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Affiliation(s)
- Takehito Ouchi
- Department of Physiology, Tokyo Dental College, 2-9-18, Kanda-Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan
- Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan
- Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA
| | - Taneaki Nakagawa
- Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan
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19
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Kotova AV, Lobov AA, Dombrovskaya JA, Sannikova VY, Ryumina NA, Klausen P, Shavarda AL, Malashicheva AB, Enukashvily NI. Comparative Analysis of Dental Pulp and Periodontal Stem Cells: Differences in Morphology, Functionality, Osteogenic Differentiation and Proteome. Biomedicines 2021; 9:1606. [PMID: 34829835 PMCID: PMC8616025 DOI: 10.3390/biomedicines9111606] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 10/28/2021] [Accepted: 10/30/2021] [Indexed: 12/18/2022] Open
Abstract
Dental stem cells are heterogeneous in their properties. Despite their common origin from neural crest stem cells, they have different functional capacities and biological functions due to niche influence. In this study, we assessed the differences between dental pulp stem cells (DPSC) and periodontal ligament stem cells (PDLSC) in their pluripotency and neuroepithelial markers transcription, morphological and functional features, osteoblast/odontoblast differentiation and proteomic profile during osteogenic differentiation. The data were collected in paired observations: two cell cultures, DPSC and PDLSC, were obtained from each donor. Both populations had the mesenchymal stem cells surface marker set exposed on their membranes but differed in Nestin (a marker of neuroectodermal origin) expression, morphology, and proliferation rate. OCT4 mRNA was revealed in DPSC and PDLSC, while OCT4 protein was present in the nuclei of DPSC only. However, transcription of OCT4 mRNA was 1000-10,000-fold lower in dental stem cells than in blastocysts. DPSC proliferated at a slower rate and have a shape closer to polygonal but they responded better to osteogenic stimuli as compared to PDLSC. RUNX2 mRNA was detected by qPCR in both types of dental stem cells but RUNX2 protein was detected by LC-MS/MS shotgun proteomics only in PDLSC suggesting the posttranscriptional regulation. DSPP and DMP1, marker genes of odontoblastic type of osteogenic differentiation, were transcribed in DPSC but not in PDLSC samples. Our results prove that DPSC and PDLSC are different in their biology and therapeutic potential: DPSC are a good candidate for osteogenic or odontogenic bone-replacement cell-seeded medicines, while fast proliferating PDLSC are a prospective candidate for other cell products.
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Affiliation(s)
- Anastasia V. Kotova
- Institute of Cytology of the Russian Academy of Sciences, 194064 St. Petersburg, Russia; (A.V.K.); (A.A.L.); (V.Y.S.); (P.K.); (A.B.M.)
- Cell Technologies Laboratory, General Dentistry Department, North-Western State Medical University, 191015 St. Petersburg, Russia;
| | - Arseniy A. Lobov
- Institute of Cytology of the Russian Academy of Sciences, 194064 St. Petersburg, Russia; (A.V.K.); (A.A.L.); (V.Y.S.); (P.K.); (A.B.M.)
| | - Julia A. Dombrovskaya
- Cell Technologies Laboratory, General Dentistry Department, North-Western State Medical University, 191015 St. Petersburg, Russia;
| | - Valentina Y. Sannikova
- Institute of Cytology of the Russian Academy of Sciences, 194064 St. Petersburg, Russia; (A.V.K.); (A.A.L.); (V.Y.S.); (P.K.); (A.B.M.)
| | | | - Polina Klausen
- Institute of Cytology of the Russian Academy of Sciences, 194064 St. Petersburg, Russia; (A.V.K.); (A.A.L.); (V.Y.S.); (P.K.); (A.B.M.)
| | - Alexey L. Shavarda
- Research Resource Center Molecular and Cell Technologies, Saint-Petersburg State University, 199034 St. Petersburg, Russia;
| | - Anna B. Malashicheva
- Institute of Cytology of the Russian Academy of Sciences, 194064 St. Petersburg, Russia; (A.V.K.); (A.A.L.); (V.Y.S.); (P.K.); (A.B.M.)
| | - Natella I. Enukashvily
- Institute of Cytology of the Russian Academy of Sciences, 194064 St. Petersburg, Russia; (A.V.K.); (A.A.L.); (V.Y.S.); (P.K.); (A.B.M.)
- Cell Technologies Laboratory, General Dentistry Department, North-Western State Medical University, 191015 St. Petersburg, Russia;
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20
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Hayashi Y, Kato H, Nonaka K, Nakanishi H. Stem cells from human exfoliated deciduous teeth attenuate mechanical allodynia in mice through distinct from the siglec-9/MCP-1-mediated tissue-repairing mechanism. Sci Rep 2021; 11:20053. [PMID: 34625639 PMCID: PMC8501097 DOI: 10.1038/s41598-021-99585-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 09/27/2021] [Indexed: 12/30/2022] Open
Abstract
The effects of stem cells from human exfoliated deciduous teeth (SHED) on mechanical allodynia were examined in mice. A single intravenous injection of SHED and conditioned medium from SHED (SHED-CM) through the left external jugular vein significantly reversed the established mechanical allodynia induced by spinal nerve transection at 6 days after injection. SHED or SHED-CM significantly decreased the mean numbers of activating transcription factor 3-positive neurons and macrophages in the ipsilateral side of the dorsal root ganglion (DRG) at 20 days after spinal nerve transection. SHED or SHED-CM also suppressed activation of microglia and astrocytes in the ipsilateral side of the dorsal spinal cord. A single intravenous injection of secreted ectodomain of sialic acid-binding Ig-like lectin-9 and monocyte chemoattractant protein-1 had no effect on the established mechanical allodynia, whereas a single intravenous injection of protein component(s) contained in SHED-CM with molecular weight of between 30 and 50 kDa reversed the pain. Therefore, it may be concluded that protein component(s) with molecular mass of 30–50 kDa secreted by SHED could protect and/or repair DRG neurons damaged by nerve transection, thereby ameliorating mechanical allodynia.
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Affiliation(s)
- Yoshinori Hayashi
- Department of Physiology, Nihon University School of Dentistry, Tokyo, 101-8310, Japan. .,Faculty of Dental Science, Department of Aging Science and Pharmacology, Kyushu University, Fukuoka, 812-8582, Japan.
| | - Hiroki Kato
- Department of Molecular Cell Biology and Oral Anatomy, Division of Oral Biological Sciences, Graduate School of Dental Science, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka, 812-8582, Japan.,Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Fukuoka, 812-8582, Japan
| | - Kazuaki Nonaka
- School of Health Sciences at Fukuoka, International University of Health and Welfare, Okawa, Fukuoka, 831-8501, Japan
| | - Hiroshi Nakanishi
- Department of Pharmacology, Faculty of Pharmacy, Yasuda Women's University, Hiroshima, 731-0153, Japan.
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21
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Capparè P, Tetè G, Sberna MT, Panina-Bordignon P. The Emerging Role of Stem Cells in Regenerative Dentistry. Curr Gene Ther 2021; 20:259-268. [PMID: 32811413 DOI: 10.2174/1566523220999200818115803] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 07/25/2020] [Accepted: 07/29/2020] [Indexed: 02/06/2023]
Abstract
Progress of modern dentistry is accelerating at a spectacular speed in the scientific, technological and clinical areas. Practical examples are the advancement in the digital field, which has guaranteed an average level of prosthetic practices for all patients, as well as other scientific developments, including research on stem cell biology. Given their plasticity, defined as the ability to differentiate into specific cell lineages with a capacity of almost unlimited self-renewal and release of trophic/immunomodulatory factors, stem cells have gained significant scientific and commercial interest in the last 15 years. Stem cells that can be isolated from various tissues of the oral cavity have emerged as attractive sources for bone and dental regeneration, mainly due to their ease of accessibility. This review will present the current understanding of emerging conceptual and technological issues of the use of stem cells to treat bone and dental loss defects. In particular, we will focus on the clinical application of stem cells, either directly isolated from oral sources or in vitro reprogrammed from somatic cells (induced pluripotent stem cells). Research aimed at further unraveling stem cell plasticity will allow to identify optimal stem cell sources and characteristics, to develop novel regenerative tools in dentistry.
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Affiliation(s)
- Paolo Capparè
- Department of Dentistry, IRCCS San Raffaele Hospital, Milan, Italy,Dental School, Vita-Salute San Raffaele University, School of Medicine, Milan, Italy
| | - Giulia Tetè
- Department of Dentistry, IRCCS San Raffaele Hospital, Milan, Italy
| | | | - Paola Panina-Bordignon
- Neuroimmunology Unit, Institute of Experimental Neurology, IRCCS San Raffaele Hospital, Milan, Italy,Dental School, Vita-Salute San Raffaele University, School of Medicine, Milan, Italy
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22
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Paes SM, Pupo YM, Cavenago BC, Fonseca-Silva T, Santos CCDO. Cryopreservation of mesenchymal stem cells derived from dental pulp: a systematic review. Restor Dent Endod 2021; 46:e26. [PMID: 34123762 PMCID: PMC8170376 DOI: 10.5395/rde.2021.46.e26] [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: 07/05/2019] [Revised: 09/22/2020] [Accepted: 09/30/2020] [Indexed: 11/11/2022] Open
Abstract
Objectives The aim of the present systematic review was to investigate the cryopreservation process of dental pulp mesenchymal stromal cells and whether cryopreservation is effective in promoting cell viability and recovery. Materials and Methods This systematic review was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the research question was determined using the population, exposure, comparison, and outcomes strategy. Electronic searches were conducted in the PubMed, Cochrane Library, Science Direct, LILACS, and SciELO databases and in the gray literature (dissertations and thesis databases and Google Scholar) for relevant articles published up to March 2019. Clinical trial studies performed with dental pulp of human permanent or primary teeth, containing concrete information regarding the cryopreservation stages, and with cryopreservation performed for a period of at least 1 week were included in this study. Results The search strategy resulted in the retrieval of 185 publications. After the application of the eligibility criteria, 21 articles were selected for a qualitative analysis. Conclusions The cryopreservation process must be carried out in 6 stages: tooth disinfection, pulp extraction, cell isolation, cell proliferation, cryopreservation, and thawing. In addition, it can be inferred that the use of dimethyl sulfoxide, programmable freezing, and storage in liquid nitrogen are associated with a high rate of cell viability after thawing and a high rate of cell proliferation in both primary and permanent teeth.
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Affiliation(s)
- Sabrina Moreira Paes
- Department of Restorative Dentistry, Universidade Federal do Paraná, Curitiba/PR, Brazil
| | - Yasmine Mendes Pupo
- Department of Restorative Dentistry, Universidade Federal do Paraná, Curitiba/PR, Brazil
| | | | - Thiago Fonseca-Silva
- Department of Dentistry, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina/MG, Brazil
| | - Carolina Carvalho de Oliveira Santos
- Department of Restorative Dentistry, Universidade Federal do Paraná, Curitiba/PR, Brazil.,Department of Dentistry, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina/MG, Brazil
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23
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Zhu S, Ying Y, He Y, Zhong X, Ye J, Huang Z, Chen M, Wu Q, Zhang Y, Xiang Z, Tu Y, Ying W, Xiao J, Li X, Ye Q, Wang Z. Hypoxia response element-directed expression of bFGF in dental pulp stem cells improve the hypoxic environment by targeting pericytes in SCI rats. Bioact Mater 2021; 6:2452-2466. [PMID: 33553827 PMCID: PMC7850944 DOI: 10.1016/j.bioactmat.2021.01.024] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 01/07/2021] [Accepted: 01/19/2021] [Indexed: 02/08/2023] Open
Abstract
Cell-based transplantation strategies possess great potential for spinal cord injury (SCI) repair. Basic fibroblast growth factor (bFGF) has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following SCI. Human dental pulp stem cells (DPSCs) are abundant stem cells with low immune rejection, which can be considered for cell replacement therapy. The purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements (5HRE) using an adeno-associated virus (AAV-5HRE-bFGF-DPSCs) in SCI repairing model. In this study, DPSCs were revealed to differentiate into CD13+ pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13+ pericytes to vascular endothelial cells. The re-attachment of CD13+ pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of protuberance. As a result, increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was improved. Thus, this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.
) 5HRE-bFGF-DPSCs secrete bFGF in a hypoxia dependent manner, making the administration more precise. CD13+ pericyte regulate vascular diameter and promote the recovery of hypoxia microenvironment via DDC-5HT-5HT-1B in SCI. 5HRE-bFGF-DPSCs can differentiate into CD13+ pericyte to compensate for the mass death of CD13+ pericyte after SCI. 5HRE-bFGF-DPSCs promote CD13+ pericyte adhesion to vascular endothelial cell by secreting bFGF through N-cadherin. 5HRE-bFGF-DPSCs promote the recovery of SCI by restoring hypoxic microenvironment and inhibit autophagy pathway.
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Affiliation(s)
- Sipin Zhu
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Yibo Ying
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Yan He
- Laboratory of Regenerative Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, 430064, China
| | - Xingxing Zhong
- The Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, China
| | - Jiahui Ye
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Zhiyang Huang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Min Chen
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Qiuji Wu
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Yifan Zhang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Ziyue Xiang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Yurong Tu
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Weiyang Ying
- Department of Pain Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China
| | - Jian Xiao
- Molecular Pharmacology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.,Research Units of Clinical Translation of Cell Growth Factors and Diseases Research, Chinese Academy of Medical Science, China
| | - Xiaokun Li
- Molecular Pharmacology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.,Research Units of Clinical Translation of Cell Growth Factors and Diseases Research, Chinese Academy of Medical Science, China
| | - Qingsong Ye
- School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325035, China.,Massachusetts General Hospital, Harvard University, Boston, 02114, USA.,Center of Regenerative Medicine, Renmin Hospital of Wuhan University, Wuhan, 630060, China
| | - Zhouguang Wang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.,Molecular Pharmacology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China
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Alipour M, Firouzi N, Aghazadeh Z, Samiei M, Montazersaheb S, Khoshfetrat AB, Aghazadeh M. The osteogenic differentiation of human dental pulp stem cells in alginate-gelatin/Nano-hydroxyapatite microcapsules. BMC Biotechnol 2021; 21:6. [PMID: 33430842 PMCID: PMC7802203 DOI: 10.1186/s12896-020-00666-3] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Accepted: 12/22/2020] [Indexed: 02/06/2023] Open
Abstract
Background Microcapsule is considered as a promising 3D microenvironment for Bone Tissue Engineering (BTE) applications. Microencapsulation of cells in an appropriate scaffold not only protected the cells against excess stress but also promoted cell proliferation and differentiation. Through the current study, we aimed to microcapsulate the human Dental Pulp Stem Cells (hDPSCs) and evaluated the proliferation and osteogenic differentiation of those cells by using MTT assay, qRT-PCR, Alkaline phosphatase, and Alizarine Red S. Results The SEM results revealed that Alg/Gel microcapsules containing nHA showed a rough and more compact surface morphology in comparison with the Alg/Gel microcapsules. Moreover, the microencapsulation by Alg/Gel/nHA could improve cell proliferation and induce osteogenic differentiation. The cells cultured in the Alg/Gel and Alg/Gel/nHA microcapsules showed 1.4-fold and 1.7-fold activity of BMP-2 gene expression more in comparison with the control group after 21 days. The mentioned amounts for the BMP-2 gene were 2.5-fold and 4-fold more expression for the Alg/Gel and Alg/Gel/nHA microcapsules after 28 days. The nHA, addition to hDPSCs-laden Alg/Gel microcapsule, could up-regulate the bone-related gene expressions of osteocalcin, osteonectin, and RUNX-2 during the 21 and 28 days through the culturing period, too. Calcium deposition and ALP activities of the cells were observed in accordance with the proliferation results as well as the gene expression analysis. Conclusion The present study demonstrated that microencapsulation of the hDPSCs inside the Alg/Gel/nHA hydrogel could be a potential approach for regenerative dentistry in the near future. Graphical abstract ![]()
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Affiliation(s)
- Mahdieh Alipour
- Dental and Periodontal Research Center, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nima Firouzi
- Stem Cell and Tissue Engineering Research Laboratory, Sahand University of Technology, Tabriz, Iran
| | - Zahra Aghazadeh
- Stem Cell Research Center and Department of Oral Medicine, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Samiei
- Department of Endodontics, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Soheila Montazersaheb
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Baradar Khoshfetrat
- Stem Cell and Tissue Engineering Research Laboratory, Sahand University of Technology, Tabriz, Iran.
| | - Marziyeh Aghazadeh
- Stem Cell Research Center and Department of Oral Medicine, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran.
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Xiao Z, Lei T, Liu Y, Yang Y, Bi W, Du H. The potential therapy with dental tissue-derived mesenchymal stem cells in Parkinson's disease. Stem Cell Res Ther 2021; 12:5. [PMID: 33407864 PMCID: PMC7789713 DOI: 10.1186/s13287-020-01957-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 09/27/2020] [Indexed: 12/19/2022] Open
Abstract
Parkinson’s disease (PD), the second most common neurodegenerative disease worldwide, is caused by the loss of dopaminergic (DAergic) neurons in the substantia nigra resulting in a series of motor or non-motor disorders. Current treatment methods are unable to stop the progression of PD and may bring certain side effects. Cell replacement therapy has brought new hope for the treatment of PD. Recently, human dental tissue-derived mesenchymal stem cells have received extensive attention. Currently, dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHED) are considered to have strong potential for the treatment of these neurodegenerative diseases. These cells are considered to be ideal cell sources for the treatment of PD on account of their unique characteristics, such as neural crest origin, immune rejection, and lack of ethical issues. In this review, we briefly describe the research investigating cell therapy for PD and discuss the application and progress of DPSCs and SHED in the treatment of PD. This review offers significant and comprehensive guidance for further clinical research on PD.
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Affiliation(s)
- Zhuangzhuang Xiao
- 112 Lab, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, 30 XueYuan Road, Haidian District, Beijing, 100083, China
| | - Tong Lei
- 112 Lab, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, 30 XueYuan Road, Haidian District, Beijing, 100083, China
| | - Yanyan Liu
- Kangyanbao (Beijing) Stem Cell Technology Co., Ltd, Beijing, 102600, China
| | - Yanjie Yang
- 112 Lab, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, 30 XueYuan Road, Haidian District, Beijing, 100083, China
| | - Wangyu Bi
- 112 Lab, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, 30 XueYuan Road, Haidian District, Beijing, 100083, China
| | - Hongwu Du
- 112 Lab, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, 30 XueYuan Road, Haidian District, Beijing, 100083, China.
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Progress in Stem Cell Therapy for Spinal Cord Injury. Stem Cells Int 2020; 2020:2853650. [PMID: 33204276 PMCID: PMC7661146 DOI: 10.1155/2020/2853650] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Revised: 10/04/2020] [Accepted: 10/21/2020] [Indexed: 02/06/2023] Open
Abstract
Background Spinal cord injury (SCI) is one of the serious neurological diseases that occur in young people with high morbidity and disability. However, there is still a lack of effective treatments for it. Stem cell (SC) treatment of SCI has gradually become a new research hotspot over the past decades. This article is aimed at reviewing the research progress of SC therapy for SCI. Methods Review the literature and summarize the effects, strategies, related mechanisms, safety, and clinical application of different SC types and new approaches in combination with SC in SCI treatment. Results A large number of studies have focused on SC therapy for SCI, most of which showed good effects. The common SC types for SCI treatment include mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), neural stem cells (NSCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs). The modes of treatment include in vivo and in vitro induction. The pathways of transplantation consist of intravenous, transarterial, nasal, intraperitoneal, intrathecal, and intramedullary injections. Most of the SC treatments for SCI use a number of cells ranging from tens of thousands to millions. Early or late SC administration, application of immunosuppressant or not are still controversies. Potential mechanisms of SC therapy include tissue repair and replacement, neurotrophy, and regeneration and promotion of angiogenesis, antiapoptosis, and anti-inflammatory. Common safety issues include thrombosis and embolism, tumorigenicity and instability, infection, high fever, and even death. Recently, some new approaches, such as the pharmacological activation of endogenous SCs, biomaterials, 3D print, and optogenetics, have been also developed, which greatly improved the application of SC therapy for SCI. Conclusion Most studies support the effects of SC therapy on SCI, while a few studies do not. The cell types, mechanisms, and strategies of SC therapy for SCI are very different among studies. In addition, the safety cannot be ignored, and more clinical trials are required. The application of new technology will promote SC therapy of SCI.
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Wang DR, Wang YH, Pan J, Tian WD. Neurotrophic effects of dental pulp stem cells in repair of peripheral nerve after crush injury. World J Stem Cells 2020; 12:1196-1213. [PMID: 33178401 PMCID: PMC7596440 DOI: 10.4252/wjsc.v12.i10.1196] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 06/13/2020] [Accepted: 08/16/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nerve diseases and injuries, which are usually accompanied by motor or sensory dysfunction and disorder, impose a heavy burden upon patients and greatly reduce their quality of life. Dental pulp stem cells (DPSCs), derived from the neural crest, have many characteristics that are similar to those of neural cells, indicating that they can be an ideal source for neural repair. AIM To explore the potential roles and molecular mechanisms of DPSCs in crushed nerve recovery. METHODS DPSCs were isolated, cultured, and identified by multilineage differentiation and flow cytometry. Western blot and immunofluorescent staining were applied to analyze the expression levels of neurotrophic proteins in DPSCs after neural induction. Then, we collected the secretions of DPSCs. We analyzed their effects on RSC96 cell proliferation and migration by CCK8 and transwell assays. Finally, we generated a sciatic nerve crush injury model in vivo and used the sciatic function index, walking track analysis, muscle weight, and hematoxylin & eosin (H&E) staining to further evaluate the nerve repair ability of DPSCs. RESULTS DPSCs highly expressed several specific neural markers, including GFAP, S100, Nestin, P75, and NF200, and were inclined toward neural differentiation. Furthermore, neural-induced DPSCs (N-DPSCs) could express neurotrophic factors, including NGF, BDNF, and GDNF. The secretions of N-DPSCs could enhance the proliferation and migration of Schwann cells. In vivo, both DPSC and N-DPSC implants alleviated gastrocnemius muscle atrophy. However, in terms of anatomy and motor function, as shown by H&E staining, immunofluorescent staining, and walking track analyses, the repair effects of N-DPSCs were more sustained, potent, and effective than those of DPSCs and the controls. CONCLUSION In summary, this study demonstrated that DPSCs are inclined to differentiate into neural cells. N-DPSCs express neurotrophic proteins that could enhance the proliferation and migration of SCs. Furthermore, our results suggested that N-DPSCs could help crushed nerves with functional recovery and anatomical repair in vivo. Thus, DPSCs or N-DPSCs could be a promising therapeutic cell source for peripheral nerve repair and regeneration.
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Affiliation(s)
- Dian-Ri Wang
- State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yu-Hao Wang
- State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jian Pan
- State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China.
| | - Wei-Dong Tian
- State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
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Wei J, Song Y, Du Z, Yu F, Zhang Y, Jiang N, Ge X. Exosomes derived from human exfoliated deciduous teeth ameliorate adult bone loss in mice through promoting osteogenesis. J Mol Histol 2020; 51:455-466. [PMID: 32656578 DOI: 10.1007/s10735-020-09896-3] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Accepted: 07/06/2020] [Indexed: 12/18/2022]
Abstract
Cell-free based therapy is an effective strategy in regenerative medicine as it avoids controversial issues, such as immunomodulation and stability. Recently, exosomes have been explored as a favorable substitution for stem cell therapy as they exhibit multiple advantages, such as the ability to be endocytosed and innate biocompatibility. This study aimed to investigate the effects of stem cells from human exfoliated deciduous teeth (SHED)-derived exosomes (SHED-Exo) on bone marrow stromal cells (BMSCs) osteogenesis and bone recovery. SHED-Exo were isolated, characterized, and applied to the bone loss area caused by periodontitis in a mouse model. We found that the injection of SHED-Exo restored bone loss to the same extent as original stem cells. Without affecting BMSCs proliferation, SHED-Exo mildly inhibited apoptosis. Moreover, SHED-Exo specifically promoted BMSCs osteogenesis and inhibited adipogenesis compared with SHED-derived conditioned medium. The expression of osteogenic marker genes, alkaline phosphatase activity, and Alizarin Red S staining of BMSCs was significantly increased by co-culturing with SHED-Exo. Moreover, Western blot analysis showed that Runx2, a key transcriptional factor in osteogenic differentiation, and p-Smad5 were upregulated upon SHED-Exo stimulation. Expression of the adipogenic marker PPARγ and the amount of lipid droplets decreased when exosomes were present. Low doses of exosomes inhibited the expression of the inflammatory cytokines IL-6 and TNF-α. In conclusion, SHED-Exo directly promoted BMSCs osteogenesis, differentiation, and bone formation. Therefore, exosomes have the potential to be utilized in the treatment of periodontitis and other bone diseases.
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Affiliation(s)
- Jizhen Wei
- Department of Periodontics, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China
- Central Laboratory, Peking University School and Hospital of Stomatology, #22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China
| | - Yeqing Song
- Central Laboratory, Peking University School and Hospital of Stomatology, #22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China
| | - Zhihao Du
- Central Laboratory, Peking University School and Hospital of Stomatology, #22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China
| | - Feiyan Yu
- Department of Oral Medicine, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China
| | - Yimei Zhang
- First Dental Center, Peking University School and Hospital of Stomatology, Beijing, China
| | - Nan Jiang
- Central Laboratory, Peking University School and Hospital of Stomatology, #22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China.
| | - Xuejun Ge
- Department of Periodontics, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China.
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Abuarqoub D, Aslam N, Almajali B, Shajrawi L, Jafar H, Awidi A. Neuro-regenerative potential of dental stem cells: a concise review. Cell Tissue Res 2020; 382:267-279. [PMID: 32725424 DOI: 10.1007/s00441-020-03255-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 07/06/2020] [Indexed: 10/23/2022]
Abstract
This review will summarize the research information regarding the regenerative potential of dental stem cells for the treatment of neurodegenerative disorders. As compared to existing treatment modalities, the stem cell therapy seems promising, and accumulating evidences about the differentiation of stem cells into various lineages are proving it. The incidence of neurodegenerative diseases such as Alzheimer's, Parkinson's, stroke, and peripheral neuropathy is increasing due to the rise in life expectancies of people which have put a huge burden on economies. Finding a promising treatment could benefit not only the patients but also the communities. Dental stem cells hold a great potential to differentiate into neuronal cells. Many studies have reported the differentiation potential of the dental stem cells with the presence of neuronal lineage markers. In this review, we conferred how the use of dental stem cells can benefit the above-mentioned bedridden diseases.
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Affiliation(s)
- Duaa Abuarqoub
- Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan. .,Cell Therapy Center, The University of Jordan, Amman, Jordan.
| | - Nazneen Aslam
- Cell Therapy Center, The University of Jordan, Amman, Jordan
| | - Bayan Almajali
- School of Medicine, The University of Jordan, Amman, Jordan
| | - Leen Shajrawi
- School of Medicine, The University of Jordan, Amman, Jordan
| | - Hanan Jafar
- Cell Therapy Center, The University of Jordan, Amman, Jordan.,School of Medicine, The University of Jordan, Amman, Jordan
| | - Abdalla Awidi
- Cell Therapy Center, The University of Jordan, Amman, Jordan. .,School of Medicine, The University of Jordan, Amman, Jordan.
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Kandalam S, De Berdt P, Ucakar B, Vanvarenberg K, Bouzin C, Gratpain V, Diogenes A, Montero-Menei CN, des Rieux A. Human dental stem cells of the apical papilla associated to BDNF-loaded pharmacologically active microcarriers (PAMs) enhance locomotor function after spinal cord injury. Int J Pharm 2020; 587:119685. [PMID: 32712253 DOI: 10.1016/j.ijpharm.2020.119685] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 07/14/2020] [Accepted: 07/20/2020] [Indexed: 02/08/2023]
Abstract
There is no treatment for spinal cord injury (SCI) that fully repairs the damages. One strategy is to inject mesenchymal stem cells around the lesion to benefit from their immunomodulatory properties and neuroprotective effect. Our hypothesis was that the combination of dental stem cells from the apical papilla (SCAP) with pharmacologically active microcarriers (PAMs) releasing brain-derived neurotrophic factor (BDNF) would improve rat locomotor function by immunomodulation and neuroprotection. BDNF-PAMs were prepared by solid/oil/water emulsion of poly(L-lactide-co-glycolide) and nanoprecipitated BDNF and subsequent coating with fibronectin. SCAP were then seeded on BDNF-PAMs. SCAP expression of neuronal and immunomodulatory factors was evaluated in vitro. SCAP BDNF-PAMs were injected in a rat spinal cord contusion model and their locomotor function was evaluated by Basso, Beattie, and Bresnahan (BBB) scoring. Impact on inflammation and neuroprotection/axonal growth was evaluated by immunofluorescence. Culture on PAMs induced the overexpression of immunomodulatory molecules and neural/neuronal markers. Injection of SCAP BDNF-PAMs at the lesion site improved rat BBB scoring, reduced the expression of inducible nitric oxide synthase and increased the expression of βIII tubulin, GAP43, and 5-HT. These results confirm the suitability and versatility of PAMs as combined drug and cell delivery system for regenerative medicine applications but also that BDNF-PAMs potentialize the very promising therapeutic potential of SCAP in the scope of SCI.
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Affiliation(s)
- Saikrishna Kandalam
- Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, UCLouvain, 1200 Bruxelles, Belgium; CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers F-49933, France
| | - Pauline De Berdt
- Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, UCLouvain, 1200 Bruxelles, Belgium
| | - Bernard Ucakar
- Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, UCLouvain, 1200 Bruxelles, Belgium
| | - Kevin Vanvarenberg
- Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, UCLouvain, 1200 Bruxelles, Belgium
| | - Caroline Bouzin
- IREC Imaging platform (2IP), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, UCLouvain, IREC, 1200 Brussels, Belgium
| | - Viridiane Gratpain
- Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, UCLouvain, 1200 Bruxelles, Belgium
| | - Anibal Diogenes
- Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
| | | | - Anne des Rieux
- Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, UCLouvain, 1200 Bruxelles, Belgium.
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Ogasawara N, Kano F, Hashimoto N, Mori H, Liu Y, Xia L, Sakamaki T, Hibi H, Iwamoto T, Tanaka E, Yamamoto A. Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental temporomandibular joint osteoarthritis. Osteoarthritis Cartilage 2020; 28:831-841. [PMID: 32272195 DOI: 10.1016/j.joca.2020.03.010] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 02/17/2020] [Accepted: 03/19/2020] [Indexed: 02/02/2023]
Abstract
OBJECTIVE Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration, abnormal bone remodeling, and chronic pain. In this study, we aimed to investigate effective therapies to reverse or suppress TMJOA progression. DESIGN To this end, we performed intravenous administration of serum free conditioned media from human exfoliated deciduous teeth stem cells (SHED-CM) into a mechanical-stress induced murine TMJOA model. RESULTS SHED-CM administration markedly suppressed temporal muscle inflammation, and improved bone integrity and surface smoothness of the destroyed condylar cartilage. Moreover, SHED-CM treatment decreased the number of IL-1β, iNOS, and MMP-13 expressing chondrocytes, whereas it specifically increased PCNA-positive cells in the multipotent polymorphic cell layer. Notably, the numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive apoptotic chondrocytes in the SHED-CM treated condyles were significantly lower than in those treated with DMEM, whereas the proteoglycan positive area was restored to a level similar to that of the sham treated group, demonstrating that SHED-CM treatment regenerated the mechanical-stress injured condylar cartilage and subchondral bone. Secretome analysis revealed that SHED-CM contained multiple therapeutic factors that act in osteochondral regeneration. CONCLUSIONS Our data demonstrated that SHED-CM treatment promoted the regeneration and repair of mechanical-stress induced mouse TMJOA. Our observations suggest that SHED-CM has potential to be a potent tissue-regenerating therapeutic agent for patients with severe TMJOA.
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Affiliation(s)
- N Ogasawara
- Department of Tissue Regeneration, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan; Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan.
| | - F Kano
- Department of Tissue Regeneration, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan.
| | - N Hashimoto
- Department of Tissue Regeneration, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan.
| | - H Mori
- Department of Pediatric Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan.
| | - Y Liu
- Department of Tissue Regeneration, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan; Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan.
| | - L Xia
- Department of Tissue Regeneration, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan; Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan.
| | - T Sakamaki
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan.
| | - H Hibi
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
| | - T Iwamoto
- Department of Pediatric Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan.
| | - E Tanaka
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan.
| | - A Yamamoto
- Department of Tissue Regeneration, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan.
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Kitase Y, Sato Y, Ueda K, Suzuki T, Mikrogeorgiou A, Sugiyama Y, Matsubara K, Tsukagoshi Okabe Y, Shimizu S, Hirata H, Yukawa H, Baba Y, Tsuji M, Takahashi Y, Yamamoto A, Hayakawa M. A Novel Treatment with Stem Cells from Human Exfoliated Deciduous Teeth for Hypoxic-Ischemic Encephalopathy in Neonatal Rats. Stem Cells Dev 2020; 29:63-74. [DOI: 10.1089/scd.2019.0221] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Affiliation(s)
- Yuma Kitase
- Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Japan
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshiaki Sato
- Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Japan
| | - Kazuto Ueda
- Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Japan
| | - Toshihiko Suzuki
- Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Japan
| | - Alkisti Mikrogeorgiou
- Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Japan
| | - Yuichiro Sugiyama
- Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Japan
| | - Kohki Matsubara
- Department of Oral and Maxillofacial Surgery and Nagoya University Hospital, Nagoya, Japan
| | | | - Shinobu Shimizu
- Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan
| | - Hitoshi Hirata
- Department of Hand Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroshi Yukawa
- Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Nagoya, Japan
- Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Nagoya, Japan
- Institute of Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan
| | - Yoshinobu Baba
- Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Nagoya, Japan
- Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Nagoya, Japan
| | - Masahiro Tsuji
- Department of Food and Nutrition, Faculty of Home Economics, Kyoto Women's University, Kyoto, Japan
| | - Yoshiyuki Takahashi
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Akihito Yamamoto
- Department of Tissue Regeneration, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Masahiro Hayakawa
- Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Japan
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Samoilova EM, Revkova VA, Brovkina OI, Kalsin VA, Melnikov PA, Konoplyannikov MA, Galimov KR, Nikitin AG, Troitskiy AV, Baklaushev VP. Chemical Reprogramming of Somatic Cells in Neural Direction: Myth or Reality? Bull Exp Biol Med 2019; 167:546-555. [PMID: 31502132 DOI: 10.1007/s10517-019-04570-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Indexed: 01/07/2023]
Abstract
In in vitro experiments on cultures of human multipotent stem cells from the human bonearrow and dental pulp, we studied direct reprogramming towards neuro-glial lineage cells using a cocktail of small molecules. Reprogramming by the previously published protocol (with a cocktail containing β-mercaptoethanol, LIF, VPA, CHIR99021, and RepSox) and by the optimized protocol (VPA, RG108, А83-01, dorsomorphin, thiazovivin, CHIR99021, forskolin, and Isx9) allows obtaining cells with immunophenotypic and genetic signs of neural stem cells. However, neither the former, nor the optimized protocols allowed preparing neural progenitors capable of adequate terminal differentiation from both bone marrow-derived mesenchymal stem cells and nestin-positive neural crest-derived mesenchymal stem cells. Real-time PCR demonstrated the expression of some neurogenesis markers, but neural stem cell-specific expression pattern was not observed. The findings lead us to a conclusion that reprogramming with small molecules without additional factors modifying gene expression does not allow reproducible production of human neural stem cell-like progenitors that can be used as the source of neural tissue for the regenerative therapy.
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Affiliation(s)
- E M Samoilova
- Federal Research Clinical Center of Specialized Medical Care, Federal Medical-Biological Agency of Russia, Moscow, Russia.
| | - V A Revkova
- Federal Research Clinical Center of Specialized Medical Care, Federal Medical-Biological Agency of Russia, Moscow, Russia
| | - O I Brovkina
- Federal Research Clinical Center of Specialized Medical Care, Federal Medical-Biological Agency of Russia, Moscow, Russia
| | - V A Kalsin
- Federal Research Clinical Center of Specialized Medical Care, Federal Medical-Biological Agency of Russia, Moscow, Russia
| | - P A Melnikov
- Federal Research Clinical Center of Specialized Medical Care, Federal Medical-Biological Agency of Russia, Moscow, Russia
- Department of Fundamental and Applied Neurobiology, V. P. Serbsky Federal Medical Research Center for Psychiatry and Narcology, Ministry of Health of the Russian Federation, Moscow, Russia
| | - M A Konoplyannikov
- Federal Research Clinical Center of Specialized Medical Care, Federal Medical-Biological Agency of Russia, Moscow, Russia
- Institute of Regenerative Medicine, I. M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - K R Galimov
- Federal Research Clinical Center of Specialized Medical Care, Federal Medical-Biological Agency of Russia, Moscow, Russia
| | - A G Nikitin
- Federal Research Clinical Center of Specialized Medical Care, Federal Medical-Biological Agency of Russia, Moscow, Russia
| | - A V Troitskiy
- Federal Research Clinical Center of Specialized Medical Care, Federal Medical-Biological Agency of Russia, Moscow, Russia
| | - V P Baklaushev
- Federal Research Clinical Center of Specialized Medical Care, Federal Medical-Biological Agency of Russia, Moscow, Russia
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Wang D, Wang Y, Tian W, Pan J. Advances of tooth-derived stem cells in neural diseases treatments and nerve tissue regeneration. Cell Prolif 2019; 52:e12572. [PMID: 30714230 PMCID: PMC6536383 DOI: 10.1111/cpr.12572] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 12/05/2018] [Accepted: 12/06/2018] [Indexed: 02/05/2023] Open
Abstract
Nerous system diseases, both central and peripheral, bring an incredible burden onto patients and enormously reduce their quality of life. Currently, there are still no effective treatments to repair nerve lesions that do not have side effects. Stem cell-based therapies, especially those using dental stem cells, bring new hope to neural diseases. Dental stem cells, derived from the neural crest, have many characteristics that are similar to neural cells, indicating that they can be an ideal source of cells for neural regeneration and repair. This review summarizes the neural traits of all the dental cell types, including DPSCs, PDLCs, DFCs, APSCs and their potential applications in nervous system diseases. We have summed up the advantages of dental stem cells in neural repair, such as their neurotrophic and neuroprotective traits, easy harvest and low rejective reaction rate, among others. Taken together, dental stem cells are an ideal cell source for neural tissue regeneration and repair.
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Affiliation(s)
- Dianri Wang
- State Key Laboratory of Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
- Department of Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Yuhao Wang
- State Key Laboratory of Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
- Department of Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Weidong Tian
- State Key Laboratory of Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
- Department of Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Jian Pan
- State Key Laboratory of Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
- Department of Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of StomatologySichuan UniversityChengduChina
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35
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Aliaghaei A, Boroujeni ME, Ahmadi H, Bayat AH, Tavirani MR, Abdollahifar MA, Pooyafar MH, Mansouri V. Dental pulp stem cell transplantation ameliorates motor function and prevents cerebellar atrophy in rat model of cerebellar ataxia. Cell Tissue Res 2019; 376:179-187. [PMID: 30635776 DOI: 10.1007/s00441-018-02980-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 12/13/2018] [Indexed: 02/07/2023]
Abstract
Cerebellar ataxias (CA) include a range of neurodegenerative disorders hallmarked by deterioration of the cerebellum. Cell replacement therapy (CRT) offers a potential remedy for the diseases associated with the central nervous system (CNS). This study was designed to assess the neurorestorative/protective effects of dental pulp stem cell (DPSC) implantation on a rat model of CA induced by 3-acetylpyridine (3-AP) as a neurotoxin. To begin, human DPSCs were extracted, cultured and phenotypically characterized. Then, experimental ataxia was induced in 20 male adult rats by a single injection of 3-AP and bilateral DPSC transplantation was performed 3 days after 3-AP administration, followed by stereological analysis of cerebellar layers along with assessment of motor skills and inflammatory response. The findings showed that transplantation of DPSCs in a 3-AP model of ataxia ameliorated motor coordination and muscle activity, increased cerebellar volumes of molecular and granular layers plus white matter, reduced the levels of inflammatory cytokines and thwarted the degeneration of Purkinje cells against 3-AP toxicity. Taken together, human DPSCs could be considered as a suitable candidate for CRT-based therapies with a specific focus on CA.
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Affiliation(s)
- Abbas Aliaghaei
- Cell Biology & Anatomical Sciences Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahdi Eskandarian Boroujeni
- Department of Stem Cells & Regenerative Medicine, Faculty of Medical Biotechnology, National Institute of Genetic Engineering & Biotechnology, Tehran, Iran
| | - Houssein Ahmadi
- Cell Biology & Anatomical Sciences Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir-Hossein Bayat
- Department of Neurobiology and Neuropsychology, Saveh University of Medical Sciences, Saveh, Iran
| | | | - Mohammad Amin Abdollahifar
- Cell Biology & Anatomical Sciences Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad H Pooyafar
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Vahid Mansouri
- Faculty of Paramedical Science, Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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36
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Preconditioning of Human Dental Pulp Stem Cells with Leukocyte- and Platelet-Rich Fibrin-Derived Factors Does Not Enhance Their Neuroregenerative Effect. Stem Cells Int 2019; 2019:8589149. [PMID: 31089335 PMCID: PMC6476049 DOI: 10.1155/2019/8589149] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Revised: 01/22/2019] [Accepted: 02/12/2019] [Indexed: 12/14/2022] Open
Abstract
Pathologies of the central nervous system are characterized by loss of brain tissue and neuronal function which cannot be adequately restored by endogenous repair processes. This stresses the need for novel treatment options such as cell-based therapies that are able to restore damaged tissue or stimulate repair. This study investigated the neuroregenerative potential of the conditioned medium of human dental pulp stem cells (CM-hDPSCs) on neural stem cell (NSC) proliferation and migration as well as on neurite outgrowth of primary cortical neurons (pCNs). Additionally, the effect of leukocyte- and platelet-rich fibrin (L-PRF) priming on the neuroregenerative potential of the hDPSC secretome on NSCs and pCNs was evaluated. L-PRF contains factors that enhance stem cell-induced regeneration, but its effect on hDPSC-mediated neuroregeneration is unknown. This study demonstrated that CM-hDPSCs enhanced neuritogenesis. Moreover, CM-hDPSCs had a chemoattractant effect on NSCs. Although priming hDPSCs with L-PRF increased brain-derived neurotrophic factor secretion, no additional effects on the paracrine-mediated repair mechanisms were observed. These data support the neuroregenerative potential of hDPSCs, and although priming had no additional effect, the potential of L-PRF-primed hDPSCs on distinct regenerative mechanisms remains to be clarified.
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Abstract
In recent years, stem cell therapy has become a very promising and advanced scientific research topic. The development of treatment methods has evoked great expectations. This paper is a review focused on the discovery of different stem cells and the potential therapies based on these cells. The genesis of stem cells is followed by laboratory steps of controlled stem cell culturing and derivation. Quality control and teratoma formation assays are important procedures in assessing the properties of the stem cells tested. Derivation methods and the utilization of culturing media are crucial to set proper environmental conditions for controlled differentiation. Among many types of stem tissue applications, the use of graphene scaffolds and the potential of extracellular vesicle-based therapies require attention due to their versatility. The review is summarized by challenges that stem cell therapy must overcome to be accepted worldwide. A wide variety of possibilities makes this cutting edge therapy a turning point in modern medicine, providing hope for untreatable diseases.
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Affiliation(s)
- Wojciech Zakrzewski
- Department of Experimental Surgery and Biomaterials Research, Wroclaw Medical University, Bujwida 44, Wrocław, 50-345 Poland
| | - Maciej Dobrzyński
- Department of Conservative Dentistry and Pedodontics, Krakowska 26, Wrocław, 50-425 Poland
| | - Maria Szymonowicz
- Department of Experimental Surgery and Biomaterials Research, Wroclaw Medical University, Bujwida 44, Wrocław, 50-345 Poland
| | - Zbigniew Rybak
- Department of Experimental Surgery and Biomaterials Research, Wroclaw Medical University, Bujwida 44, Wrocław, 50-345 Poland
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38
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Dos Santos FP, Peruch T, Katami SJV, Martini APR, Crestani TA, Quintiliano K, Maurmann N, Sanches EF, Netto CA, Pranke P, de Souza Pagnussat A. Poly (lactide-co-glycolide) (PLGA) Scaffold Induces Short-term Nerve Regeneration and Functional Recovery Following Sciatic Nerve Transection in Rats. Neuroscience 2018; 396:94-107. [PMID: 30452974 DOI: 10.1016/j.neuroscience.2018.11.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 11/06/2018] [Accepted: 11/08/2018] [Indexed: 01/27/2023]
Abstract
Peripheral nerve injury is an important cause of incapability and has limited available treatment. Autologous donor nerve implant is the golden standard treatment, however, may cause secondary deficits. Stem cells show positive results in preclinical settings, preserving tissue and function. We tested the efficacy of stem cells derived from human exfoliated deciduous teeth seeded in poly (lactide-co-glycolide) scaffolds in sciatic nerve transection model. Seventy-two adult male Wistar rats had 7-mm nerve gap bridge using scaffolds with (or without) stem cells. Animals were randomly divided into: sham-operated; sham-operated without scaffold; sham-operated + scaffold + stem cells; sciatic transection + no treatment; sciatic transection + acellular scaffolds; sciatic transection + scaffold + stem cells. Sciatic Functional Index and Ladder Rung Walking tests were performed before (-1), 14 and 28 days after surgery. Morphometric nerve measurement and muscle weights were assessed. Scaffolds with stem cells improved function in Sciatic Functional Index. Acellular scaffold was effective, promoting functional recovery and nerve regeneration following nerve injury. Scaffolds provide better nerve regeneration and functional recovery after sciatic transection. Despite cell therapy promoting faster recovery after sciatic transection in the Sciatic Index Score, stem cells did not improve functional and morphological recovery after nerve injury. This is the first study testing the potential use of scaffolds combined with stem cells in the early stages after injury. Scaffolds with stem cells could accelerate nerve recovery and favor adjuvant therapies, evidencing the need for further studies to increase the knowledge about stem cells' mechanisms.
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Affiliation(s)
- Franciele Pereira Dos Santos
- Post-graduation Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Thais Peruch
- Department of Physical Therapy, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | | | - Ana Paula Rodrigues Martini
- Post-graduation Program in Neuroscience, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Thayane Antoniolli Crestani
- Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Post-graduation Program in Neuroscience, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Kerlin Quintiliano
- Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Post-graduation Program in Neuroscience, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Natasha Maurmann
- Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Post-graduation Program in Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Eduardo Farias Sanches
- Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Post-graduation Program in Neuroscience, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
| | - Carlos Alexandre Netto
- Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Patricia Pranke
- Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Post-graduation Program in Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Stem Cell Research Institute (SCRI), Porto Alegre, RS, Brazil
| | - Aline de Souza Pagnussat
- Post-graduation Program in Rehabilitation Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil; Department of Physical Therapy, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil; Post-graduation Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
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Raza SS, Wagner AP, Hussain YS, Khan MA. Mechanisms underlying dental-derived stem cell-mediated neurorestoration in neurodegenerative disorders. Stem Cell Res Ther 2018; 9:245. [PMID: 30257724 PMCID: PMC6158826 DOI: 10.1186/s13287-018-1005-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Neurodegenerative disorders have a complex pathology and are characterized by a progressive loss of neuronal architecture in the brain or spinal cord. Neuroprotective agents have demonstrated promising results at the preclinical stage, but this has not been confirmed at the clinical stage. Thus far, no neuroprotective drug that can prevent neuronal degeneration in patients with neurodegenerative disorders is available. MAIN BODY Recent studies have focused on neurorestorative measures, such as cell-based therapy, rather than neuroprotective treatment. The utility of cell-based approaches for the treatment of neurodegenerative disorders has been explored extensively, and the results have been somewhat promising with regard to reversing the outcome. Because of their neural crest origin, ease of harvest, accessibility, ethical suitability, and potential to differentiate into the neurogenic lineage, dental-derived stem cells (DSCs) have become an attractive source for cell-based neurorestoration therapies. In the present review, we summarize the possible use of DSC-based neurorestoration therapy as an alternative treatment for neurodegenerative disorders, with a particular emphasis on the mechanism underlying recovery in neurodegenerative disorders. CONCLUSION Transplantation research in neurodegenerative diseases should aim to understand the mechanism providing benefits both at the molecular and functional level. Due to their ease of accessibility, plasticity, and ethical suitability, DSCs hold promise to overcome the existing challenges in the field of neurodegeneration through multiple mechanisms, such as cell replacement, bystander effect, vasculogenesis, synaptogenesis, immunomodulation, and by inhibiting apoptosis.
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Affiliation(s)
- Syed Shadab Raza
- Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era Medical College & Hospital, Era University, Lucknow, Uttar Pradesh, 226003, India. .,Department of Stem Cell Biology and Regenerative Medicine, Era University, Lucknow, 226003, India.
| | - Aurel Popa Wagner
- Departmentof Dental Materials, RUHS College of Dental Sciences, Subhash Nagar, Jaipur, Rajasthan, 302002, India.,Center of Clinical and Experimental Medicine, University of Medicine and Pharmacy Craiova, Craiova, Romania.,School of Medicine, Griffith University, Southport, QLD, Australia
| | - Yawer S Hussain
- Department of Neurology, Chair of Vascular Neurology and Dementia, Essen University Hospital, Essen, Germany
| | - Mohsin Ali Khan
- Era Medical College & Hospital, Era University, Lucknow, Uttar Pradesh, 226003, India
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40
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Zhai Q, Dong Z, Wang W, Li B, Jin Y. Dental stem cell and dental tissue regeneration. Front Med 2018; 13:152-159. [PMID: 29971640 DOI: 10.1007/s11684-018-0628-x] [Citation(s) in RCA: 122] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Accepted: 12/14/2017] [Indexed: 12/22/2022]
Abstract
The teeth are highly differentiated chewing organs formed by the development of tooth germ tissue located in the jaw and consist of the enamel, dentin, cementum, pulp, and periodontal tissue. Moreover, the teeth have a complicated regulatory mechanism, special histologic origin, diverse structure, and important function in mastication, articulation, and aesthetics. These characteristics, to a certain extent, greatly complicate the research in tooth regeneration. Recently, new ideas for tooth and tissue regeneration have begun to appear with rapid developments in the theories and technologies in tissue engineering. Numerous types of stem cells have been isolated from dental tissue, such as dental pulp stem cells (DPSCs), stem cells isolated from human pulp of exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAPs), and dental follicle cells (DFCs). All these cells can regenerate the tissue of tooth. This review outlines the cell types and strategies of stem cell therapy applied in tooth regeneration, in order to provide theoretical basis for clinical treatments.
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Affiliation(s)
- Qiming Zhai
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Center for Tissue Engineering, Fourth Military Medical University, Xi'an, 710032, China
| | - Zhiwei Dong
- Department of Oral and Maxillofacial Surgery, General Hospital of Shenyang Military Area Command, Shenyang, 110840, China
| | - Wei Wang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry and Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China
| | - Bei Li
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Center for Tissue Engineering, Fourth Military Medical University, Xi'an, 710032, China. .,Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, 710032, China.
| | - Yan Jin
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Center for Tissue Engineering, Fourth Military Medical University, Xi'an, 710032, China. .,Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, 710032, China.
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41
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Potential Roles of Dental Pulp Stem Cells in Neural Regeneration and Repair. Stem Cells Int 2018; 2018:1731289. [PMID: 29853908 PMCID: PMC5964589 DOI: 10.1155/2018/1731289] [Citation(s) in RCA: 98] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 03/22/2018] [Indexed: 12/22/2022] Open
Abstract
This review summarizes current advances in dental pulp stem cells (DPSCs) and their potential applications in the nervous diseases. Injured adult mammalian nervous system has a limited regenerative capacity due to an insufficient pool of precursor cells in both central and peripheral nervous systems. Nerve growth is also constrained by inhibitory factors (associated with central myelin) and barrier tissues (glial scarring). Stem cells, possessing the capacity of self-renewal and multicellular differentiation, promise new therapeutic strategies for overcoming these impediments to neural regeneration. Dental pulp stem cells (DPSCs) derive from a cranial neural crest lineage, retain a remarkable potential for neuronal differentiation, and additionally express multiple factors that are suitable for neuronal and axonal regeneration. DPSCs can also express immunomodulatory factors that stimulate formation of blood vessels and enhance regeneration and repair of injured nerve. These unique properties together with their ready accessibility make DPSCs an attractive cell source for tissue engineering in injured and diseased nervous systems. In this review, we interrogate the neuronal differentiation potential as well as the neuroprotective, neurotrophic, angiogenic, and immunomodulatory properties of DPSCs and its application in the injured nervous system. Taken together, DPSCs are an ideal stem cell resource for therapeutic approaches to neural repair and regeneration in nerve diseases.
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42
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Ebrahimi M, Botelho M. Adult Stem Cells of Orofacial Origin: Current Knowledge and Limitation and Future Trend in Regenerative Medicine. Tissue Eng Regen Med 2017; 14:719-733. [PMID: 30603522 PMCID: PMC6171671 DOI: 10.1007/s13770-017-0078-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Revised: 07/19/2017] [Accepted: 08/04/2017] [Indexed: 12/21/2022] Open
Abstract
Stem cell research is one of the most rapidly expanding field of medicine which provides significant opportunities for therapeutic and regenerative applications. Different types of stem cells have been isolated investigating their accessibility, control of the differentiation pathway and additional immunomodulatory properties. Bulk of the literature focus has been on the study and potential applications of adult stem cells (ASC) because of their low immunogenicity and reduced ethical considerations. This review paper summarizes the basic available literature on different types of ASC with special focus on stem cells from dental and orofacial origin. ASC have been isolated from different sources, however, isolation of ASC from orofacial tissues has provided a novel promising alternative. These cells offer a great potential in the future of therapeutic and regenerative medicine because of their remarkable availability at low cost while allowing minimally invasive isolation procedures. Furthermore, their immunomodulatory and anti-inflammatory potential is of particular interest. However, there are conflicting reports in the literature regarding their particular biology and full clinical potentials. Sound knowledge and higher control over proliferation and differentiation mechanisms are prerequisites for clinical applications of these cells. Therefore, further standardized basic and translational studies are required to increase the reproducibility and reduce the controversies of studies, which in turn facilitate comparison of related literature and enhance further development in the field.
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Affiliation(s)
- Mehdi Ebrahimi
- Department of Oral Rehabilitation, Faculty of Dentistry, Prince Philip Dental Hospital, The University of Hong Kong, 34 Hospital Road, Sai Ying Pun, Hong Kong
| | - Michael Botelho
- Department of Oral Rehabilitation, Faculty of Dentistry, Prince Philip Dental Hospital, The University of Hong Kong, 34 Hospital Road, Sai Ying Pun, Hong Kong
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Libro R, Bramanti P, Mazzon E. The combined strategy of mesenchymal stem cells and tissue-engineered scaffolds for spinal cord injury regeneration. Exp Ther Med 2017; 14:3355-3368. [PMID: 29042919 PMCID: PMC5639409 DOI: 10.3892/etm.2017.4939] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Accepted: 08/03/2017] [Indexed: 01/02/2023] Open
Abstract
Spinal cord injury (SCI) is a traumatic lesion that can result in the loss of motor or sensory neurons. Stem cell (SC)-based therapies have been demonstrated to promote neuronal regeneration following SCI, by releasing a range of trophic factors that support endogenous repair or by differentiating into neurons, or glial cells in order to replace the damaged cells. However, numerous limitations remain for therapies based on SC transplantion alone, including a low rate of survival/engraftment. Nevertheless, scaffolds are 3-dimentional substrates that have revealed to support cell survival, proliferation and differentiation in vivo, by mimicking a more favorable endogenous microenvironment. A multidisciplinary approach, which combines engineered scaffolds with SCs has been proposed as a promising strategy for encouraging spinal cord regeneration. The present review has focused on the regenerative potential of mesenchymal SCs isolated from different sources and combined with various scaffold types, in preclinical and clinical SCI studies.
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Affiliation(s)
- Rosaliana Libro
- Department of Experimental Neurology, IRCCS Centro Neurolesi ‘Bonino-Pulejo’, I-98124 Messina, Italy
| | - Placido Bramanti
- Department of Experimental Neurology, IRCCS Centro Neurolesi ‘Bonino-Pulejo’, I-98124 Messina, Italy
| | - Emanuela Mazzon
- Department of Experimental Neurology, IRCCS Centro Neurolesi ‘Bonino-Pulejo’, I-98124 Messina, Italy
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44
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Interferon-γ is a master checkpoint regulator of cytokine-induced differentiation. Proc Natl Acad Sci U S A 2017; 114:E6867-E6874. [PMID: 28760993 DOI: 10.1073/pnas.1706915114] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Cytokines are protein mediators that are known to be involved in many biological processes, including cell growth, survival, inflammation, and development. To study their regulation, we generated a library of 209 different cytokines. This was used in a combinatorial format to study the effects of cytokines on each other, with particular reference to the control of differentiation. This study showed that IFN-γ is a master checkpoint regulator for many cytokines. It operates via an autocrine mechanism to elevate STAT1 and induce internalization of gp130, a common component of many heterodimeric cytokine receptors. This targeting of a receptor subunit that is common to all members of an otherwise diverse family solves the problem of how a master regulator can control so many diverse receptors. When one adds an autocrine mechanism, fine control at the level of individual cells is achieved.
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45
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Gervois P, Wolfs E, Dillen Y, Hilkens P, Ratajczak J, Driesen R, Vangansewinkel T, Bronckaers A, Brône B, Struys T, Lambrichts I. Paracrine Maturation and Migration of SH-SY5Y Cells by Dental Pulp Stem Cells. J Dent Res 2017; 96:654-662. [DOI: 10.1177/0022034517690491] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Neurological disorders are characterized by neurodegeneration and/or loss of neuronal function, which cannot be adequately repaired by the host. Therefore, there is need for novel treatment options such as cell-based therapies that aim to salvage or reconstitute the lost tissue or that stimulate host repair. The present study aimed to evaluate the paracrine effects of human dental pulp stem cells (hDPSCs) on the migration and neural maturation of human SH-SY5Y neuroblastoma cells. The hDPSC secretome had a significant chemoattractive effect on SH-SY5Y cells as shown by a transwell assay. To evaluate neural maturation, SH-SY5Y cells were first induced toward neuronal cells, after which they were exposed to the hDPSC secretome. In addition, SH-SY5Y cells subjected to the hDPSC secretome showed increased neuritogenesis compared with nonexposed cells. Maturated cells were shown to increase immune reactivity for neuronal markers compared with controls. Ultrastructurally, retinoic acid (RA) signaling and subsequent exposure to the hDPSC secretome induced a gradual rise in metabolic activity and neuronal features such as multivesicular bodies and cytoskeletal elements associated with cellular communication. In addition, electrophysiological recordings of differentiating cells demonstrated a transition toward a neuronal electrophysiological profile based on the maximum tetrodotoxin (TTX)–sensitive, Na+ current. Moreover, conditioned medium (CM)–hDPSC–maturated SH-SY5Y cells developed distinct features including, Cd2+-sensitive currents, which suggests that CM-hDPSC–maturated SH-SY5Y acquired voltage-gated Ca2+ channels. The results reported in this study demonstrate the potential of hDPSCs to support differentiation and recruitment of cells with neuronal precursor characteristics in a paracrine manner. Moreover, this in vitro experimental design showed that the widely used SH-SY5Y cell line can improve and simplify the preclinical in vitro research on the molecular mechanisms of stem cell–mediated neuronal regeneration.
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Affiliation(s)
- P. Gervois
- Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - E. Wolfs
- Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - Y. Dillen
- Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - P. Hilkens
- Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - J. Ratajczak
- Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - R.B. Driesen
- Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - T. Vangansewinkel
- Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - A. Bronckaers
- Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - B. Brône
- Group of Physiology, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - T. Struys
- Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - I. Lambrichts
- Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
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46
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Nozaki T, Ohura K. Inhibition of <i>miR-183</i> Induces Insulin in Dental Pulp Cells. J HARD TISSUE BIOL 2017. [DOI: 10.2485/jhtb.26.319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Tadashige Nozaki
- Department of Pharmacology, Faculty of Dentistry, Osaka Dental University
| | - Kiyoshi Ohura
- Department of Pharmacology, Faculty of Dentistry, Osaka Dental University
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47
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Chalisserry EP, Nam SY, Park SH, Anil S. Therapeutic potential of dental stem cells. J Tissue Eng 2017; 8:2041731417702531. [PMID: 28616151 PMCID: PMC5461911 DOI: 10.1177/2041731417702531] [Citation(s) in RCA: 123] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 03/12/2017] [Indexed: 12/13/2022] Open
Abstract
Stem cell biology has become an important field in regenerative medicine and tissue engineering therapy since the discovery and characterization of mesenchymal stem cells. Stem cell populations have also been isolated from human dental tissues, including dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla, dental follicle progenitor cells, and periodontal ligament stem cells. Dental stem cells are relatively easily obtainable and exhibit high plasticity and multipotential capabilities. The dental stem cells represent a gold standard for neural-crest-derived bone reconstruction in humans and can be used for the repair of body defects in low-risk autologous therapeutic strategies. The bioengineering technologies developed for tooth regeneration will make substantial contributions to understand the developmental process and will encourage future organ replacement by regenerative therapies in a wide variety of organs such as the liver, kidney, and heart. The concept of developing tooth banking and preservation of dental stem cells is promising. Further research in the area has the potential to herald a new dawn in effective treatment of notoriously difficult diseases which could prove highly beneficial to mankind in the long run.
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Affiliation(s)
- Elna Paul Chalisserry
- Interdisciplinary Program of Marine-Bio, Electrical & Mechanical Engineering, Pukyong National University, Busan, Korea
- Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, Korea
| | - Seung Yun Nam
- Interdisciplinary Program of Marine-Bio, Electrical & Mechanical Engineering, Pukyong National University, Busan, Korea
- Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, Korea
- Department of Biomedical Engineering, Pukyong National University, Busan, South Korea
| | - Sang Hyug Park
- Interdisciplinary Program of Marine-Bio, Electrical & Mechanical Engineering, Pukyong National University, Busan, Korea
- Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, Korea
- Department of Biomedical Engineering, Pukyong National University, Busan, South Korea
| | - Sukumaran Anil
- Division of Periodontics, Department of Preventive Dental Sciences, College of Dentistry Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
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48
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Ahmed NEMB, Murakami M, Kaneko S, Nakashima M. The effects of hypoxia on the stemness properties of human dental pulp stem cells (DPSCs). Sci Rep 2016; 6:35476. [PMID: 27739509 PMCID: PMC5064411 DOI: 10.1038/srep35476] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2016] [Accepted: 09/30/2016] [Indexed: 12/21/2022] Open
Abstract
Recent studies have demonstrated that culture under hypoxia has beneficial effects on mesenchymal stem cells (MSCs). However, there are limitations to achieving a stable condition in conventional hypoxic CO2 incubators. DPSCs are a unique type of MSCs which are promising in many regenerative therapies. In this study, we investigated the ideal hypoxic culture environment for DPSCs using a new system that can provide controlled O2 environment. The effects of hypoxia (3%, 5%) on the stemness properties of DPSCs. Their morphology, proliferation rate, expression of stem cell markers, migration ability, mRNA expression of angiogenic/neurotrophic factors and immunomodulatory genes were evaluated and compared. Additionally, the effect of the discrete secretome on proliferation, migration, and neurogenic induction was assessed. Hypoxic DPSCs were found to be smaller in size and exhibited larger nuclei. 5% O2 significantly increased the proliferation rate, migration ability, expression of stem cell markers (CXCR4 and G-CSFR), and expression of SOX2, VEGF, NGF, and BDNF genes of DPSCs. Moreover, secretome collected from 5%O2 cultures displayed higher stimulatory effects on proliferation and migration of NIH3T3 cells and on neuronal differentiation of SH-SY5Y cells. These results demonstrate that 5%O2 may be ideal for enhancing DPSCs growth, stem cell properties, and secretome trophic effect.
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Affiliation(s)
- Nermeen El-Moataz Bellah Ahmed
- Department of Stem Cell Biology and Regenerative Medicine, National Center for Geriatrics and Gerontology, Research Institute, Obu, Aichi, Japan.,Department of Oro-dental genetics, Division of Human Genetics and Human Genome, National research center, Cairo, Egypt
| | - Masashi Murakami
- Department of Stem Cell Biology and Regenerative Medicine, National Center for Geriatrics and Gerontology, Research Institute, Obu, Aichi, Japan
| | - Satoru Kaneko
- Reproduction Center, Gynecology, Ichikawa General Hospital, Tokyo Dental College, Sugano, Ichikawa, Chiba, Japan
| | - Misako Nakashima
- Department of Stem Cell Biology and Regenerative Medicine, National Center for Geriatrics and Gerontology, Research Institute, Obu, Aichi, Japan
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49
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Hirata M, Ishigami M, Matsushita Y, Ito T, Hattori H, Hibi H, Goto H, Ueda M, Yamamoto A. Multifaceted Therapeutic Benefits of Factors Derived From Dental Pulp Stem Cells for Mouse Liver Fibrosis. Stem Cells Transl Med 2016; 5:1416-1424. [PMID: 27280796 DOI: 10.5966/sctm.2015-0353] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Accepted: 05/10/2016] [Indexed: 02/07/2023] Open
Abstract
: Chronic liver injury from various causes often results in liver fibrosis (LF). Although the liver possesses endogenous tissue-repairing activities, these can be overcome by sustained inflammation and excessive fibrotic scar formation. Advanced LF leads to irreversible cirrhosis and subsequent liver failure and/or hepatic cancer. Here, using the mouse carbon tetrachloride (CCl4)-induced LF model, we showed that a single intravenous administration of stem cells derived from human exfoliated deciduous teeth (SHEDs) or of SHED-derived serum-free conditioned medium (SHED-CM) resulted in fibrotic scar resolution. SHED-CM suppressed the gene expression of proinflammatory mediators, such as TNF-α, IL-1β, and iNOS, and eliminated activated hepatic stellate cells by inducing their apoptosis, but protected parenchymal hepatocytes from undergoing apoptosis. In addition, SHED-CM induced tissue-repairing macrophages that expressed high levels of the profibrinolytic factor, matrix metalloproteinase 13. Furthermore, SHED-CM suppressed the CCl4-induced apoptosis of primary cultured hepatocytes. SHED-CM contained a high level of hepatocyte growth factor (HGF). Notably, HGF-depleted SHED-CM (dHGF-CM) did not suppress the proinflammatory response or resolve fibrotic scarring. Furthermore, SHED-CM, but not dHGF-CM, inhibited CCl4-induced hepatocyte apoptosis. These results suggest that HGF plays a central role in the SHED-CM-mediated resolution of LF. Taken together, our findings suggest that SHED-CM provides multifaceted therapeutic benefits for the treatment of LF. SIGNIFICANCE This study demonstrated that a single intravenous administration of stem cells from human exfoliated deciduous teeth (SHEDs) or of the serum-free conditioned medium (CM) derived from SHEDs markedly improved mouse liver fibrosis (LF). SHED-CM suppressed chronic inflammation, eliminated activated hepatic stellate cells by inducing their apoptosis, protected hepatocytes from undergoing apoptosis, and induced differentiation of tissue-repairing macrophages expressing high levels of the profibrinolytic factor matrix metalloproteinase 13. Furthermore, hepatocyte growth factor played a central role in the SHED-CM-mediated resolution of LF. This is the first report demonstrating the multifaceted therapeutic benefits of secreted factors derived from SHEDs for LF.
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Affiliation(s)
- Marina Hirata
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshihiro Matsushita
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hisashi Hattori
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hideharu Hibi
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hidemi Goto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Minoru Ueda
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Akihito Yamamoto
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
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50
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Clonal Heterogeneity in the Neuronal and Glial Differentiation of Dental Pulp Stem/Progenitor Cells. Stem Cells Int 2016; 2016:1290561. [PMID: 27313623 PMCID: PMC4899607 DOI: 10.1155/2016/1290561] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Revised: 03/24/2016] [Accepted: 05/08/2016] [Indexed: 12/22/2022] Open
Abstract
Cellular heterogeneity presents an important challenge to the development of cell-based therapies where there is a fundamental requirement for predictable and reproducible outcomes. Transplanted Dental Pulp Stem/Progenitor Cells (DPSCs) have demonstrated early promise in experimental models of spinal cord injury and stroke, despite limited evidence of neuronal and glial-like differentiation after transplantation. Here, we report, for the first time, on the ability of single cell-derived clonal cultures of murine DPSCs to differentiate in vitro into immature neuronal-like and oligodendrocyte-like cells. Importantly, only DPSC clones with high nestin mRNA expression levels were found to successfully differentiate into Map2 and NF-positive neuronal-like cells. Neuronally differentiated DPSCs possessed a membrane capacitance comparable with primary cultured striatal neurons and small inward voltage-activated K(+) but not outward Na(+) currents were recorded suggesting a functionally immature phenotype. Similarly, only high nestin-expressing clones demonstrated the ability to adopt Olig1, Olig2, and MBP-positive immature oligodendrocyte-like phenotype. Together, these results demonstrate that appropriate markers may be used to provide an early indication of the suitability of a cell population for purposes where differentiation into a specific lineage may be beneficial and highlight that further understanding of heterogeneity within mixed cellular populations is required.
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