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Yang Y, Akdemir AR, Rashik RA, Shihadeh Khater OA, Weng Z, Wang L, Zhong Y, Gallant ND. Guided neural stem cell differentiation by dynamic loading of 3D printed elastomeric scaffolds. J Mech Behav Biomed Mater 2025; 165:106940. [PMID: 39955829 DOI: 10.1016/j.jmbbm.2025.106940] [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: 12/10/2024] [Revised: 01/22/2025] [Accepted: 02/09/2025] [Indexed: 02/18/2025]
Abstract
The limited regenerative ability of "permanent" cells is a major barrier to treating conditions like spinal cord injury (SCI) and myocardial infarction (MI). The delivery of stem cells, which can generate various cell types, offer potential for personalized therapy with reduced immunoreaction and recovery time. However, restoring function to these tissues also requires new or replacement cells to align properly. Neurons, for example, must organize and extend parallel axons, mimicking their natural structure for directional signal propagation. Current stem cell differentiation methods lack guidance, resulting in randomly distributed axons and limited repair effectiveness. Advancing methods and materials to guide stem cell differentiation into functional, aligned nerve bundles is crucial for improving SCI treatment outcomes. This study aimed to develop an in vitro system to promote aligned neural differentiation by applying cyclic uniaxial tension to PC-12 stem cells adhered to 3D-printed elastic scaffolds. We created a simple loading device which can apply cyclic and controllable stretching force to a scaffold, which in turn transmits uniaxial tension to cells adhered to the scaffold during their differentiation. An elastomer ink for 3D printing scaffolds was formulated and surface treatment processes were investigated to enhance the cell-scaffold adhesion to support the dynamic loading. It was revealed that a corona discharge treatment while the scaffold is soaked with type I collagen can significantly enhance cell adhesion. A range of strain magnitudes and frequencies were revealed to enhance the differentiation of neural tissue derived PC-12 cells to neuron cells and increase the length of their neurites up to 76%. The combination of 3% maximum strain and 1 Hz loading frequency maximized differentiation and neurite extension. These findings demonstrate that dynamic mechanical stimulation enhances neural differentiation and organization, offering an alternative approach for regenerative therapies targeting SCI and similar conditions.
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Affiliation(s)
- Yi Yang
- Department of Mechanical Engineering, University of South Florida, 4202 E. Fowler Ave, Tampa, FL, 33620, USA
| | - Abdullah Revaha Akdemir
- Department of Mechanical Engineering, University of South Florida, 4202 E. Fowler Ave, Tampa, FL, 33620, USA
| | - Rafsan Ahmed Rashik
- Department of Mechanical Engineering, University of South Florida, 4202 E. Fowler Ave, Tampa, FL, 33620, USA
| | - Omar Ahmad Shihadeh Khater
- Department of Mechanical Engineering, University of South Florida, 4202 E. Fowler Ave, Tampa, FL, 33620, USA
| | - Zijian Weng
- Department of Mechanical Engineering, University of South Florida, 4202 E. Fowler Ave, Tampa, FL, 33620, USA
| | - Long Wang
- Department of Civil and Environmental Engineering, California Polytechnic State University, San Luis Obispo, CA, 93407, USA
| | - Ying Zhong
- Sauvage Laboratory for Smart Materials, School of Integrated Circuits, Harbin Institute of Technology (Shenzhen), University Town of Shenzhen, Shenzhen, Guangdong, 518055, China.
| | - Nathan D Gallant
- Department of Mechanical Engineering, University of South Florida, 4202 E. Fowler Ave, Tampa, FL, 33620, USA.
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Sousa CS, Monteiro A, Salgado AJ, Silva NA. Combinatorial therapies for spinal cord injury repair. Neural Regen Res 2025; 20:1293-1308. [PMID: 38845223 PMCID: PMC11624878 DOI: 10.4103/nrr.nrr-d-24-00061] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 03/28/2024] [Accepted: 05/02/2024] [Indexed: 07/31/2024] Open
Abstract
Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.
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Affiliation(s)
- Carla S. Sousa
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar – gualtar, Braga, Portugal
- ICVS/3B’s Associate Lab, PT Government Associated Lab, Campus de Gualtar – gualtar, Braga, Portugal
| | - Andreia Monteiro
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar – gualtar, Braga, Portugal
- ICVS/3B’s Associate Lab, PT Government Associated Lab, Campus de Gualtar – gualtar, Braga, Portugal
| | - António J. Salgado
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar – gualtar, Braga, Portugal
- ICVS/3B’s Associate Lab, PT Government Associated Lab, Campus de Gualtar – gualtar, Braga, Portugal
| | - Nuno A. Silva
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar – gualtar, Braga, Portugal
- ICVS/3B’s Associate Lab, PT Government Associated Lab, Campus de Gualtar – gualtar, Braga, Portugal
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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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Saberian E, Jenča A, Jenča A, Zare-Zardini H, Araghi M, Petrášová A, Jenčová J. Applications of artificial intelligence in regenerative dentistry: promoting stem cell therapy and the scaffold development. Front Cell Dev Biol 2024; 12:1497457. [PMID: 39712572 PMCID: PMC11659669 DOI: 10.3389/fcell.2024.1497457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 11/25/2024] [Indexed: 12/24/2024] Open
Abstract
Tissue repair represents a critical concern within the domain of dentistry. On a daily basis, countless individuals seek dental clinic services due to inadequate dental care. Many of the treatments that patients receive have unfavorable side effects. The employment of innovative methodologies, including gene therapy, tissue engineering, and stem cell (SCs) applications for regenerative purposes, has garnered significant interest over the past years. In recent times, artificial intelligence, particularly neural networks, has emerged as a topic of considerable attention among many medical professionals. Artificial intelligence possesses the capability to analyze data patterns through learning algorithms. Research opportunities in the rapidly expanding field of health sciences have been made possible by the use of artificial intelligence (AI) technologies. Though its uses are not restricted to these situations, artificial intelligence (AI) has the potential to improve and accelerate many aspects of regenerative medicine research and development, especially when working with complicated patterns. This review article is to investigate how artificial intelligence might be used to enhance regenerative processes in dentistry by using scaffolds and stem cells, in light of the continuous advances in artificial intelligence in the fields of medicine and tissue regeneration. It highlights the difficulties that still exist in this developing sector and explores the possible uses of AI with a particular emphasis on dentistry practices.
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Affiliation(s)
- Elham Saberian
- Klinika of Stomatology and Maxillofacial Surgery Akadémia Košice Bacikova, Pavol Jozef Šafárik University, Kosice, Slovakia
| | - Andrej Jenča
- Klinika of Stomatology and Maxillofacial Surgery Akadémia Košice Bacikova, UPJS LF, Kosice, Slovakia
| | - Andrej Jenča
- Klinika of Stomatology and Maxillofacial Surgery Akadémia Košice Bacikova, UPJS LF, Kosice, Slovakia
| | - Hadi Zare-Zardini
- Department of Biomedical Engineering, Meybod University, Meybod, Iran
| | - Mohammad Araghi
- Department of Computer Engineering, The University of Tehran, Tehran, Iran
| | - Adriána Petrášová
- Klinika of Stomatology and Maxillofacial Surgery Akadémia Košice Bacikova, Pavol Jozef Safarik University, Kosice, Slovakia
| | - Janka Jenčová
- Klinika of Stomatology and Maxillofacial Surgery Akadémia Košice Bacikova, UPJS LF, Kosice, Slovakia
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Yu L, Jin H, Xia H, Wang X, Wang L, Li D, Zhao J, Sang Y, Qiu J, Lu N, Liu H, Yang N. Polylactic acid/chitosan-IKVAV Janus film serving as a dual functional platform for spinal cord injury repair. NANOSCALE 2024; 16:21991-22000. [PMID: 39513718 DOI: 10.1039/d4nr02248c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
The repair of traumatic spinal cord injury (SCI) remains a challenge due to the non-regenerative nature of functional neurons in adults. Neural stem cell (NSC)-based therapy has emerged as a promising approach for the treatment of SCI by replacing the damaged neurons with differentiated stem cells. However, directing the neuronal differentiation of implanted stem cells in the injury microenvironment is of great difficulty, especially considering that SCI is generally associated with severe fibrotic tissue infiltration, neuron inflammation, and tissue adhesion. Here, we propose a dual functional Janus film capable of preventing tissue adhesion and promoting the neuronal differentiation of stem cells for the treatment of SCI. The Janus film is composed of a layer of polylactic acid (PLA) and a layer of chitosan (CS) grafted with IKVAV peptides. The PLA layer prevents the invasion of the fibrotic tissue, while the IKVAV peptide-grafted CS layer offers support for NSC implantation and thus the neuronal differentiation of the NSCs. When serving as the dura patch, the Janus films seeded with NSCs promote the recovery of motor function and the regeneration of the injured spinal cord tissue of SCI rats. This dual functional Janus film holds great promise for treating SCI in combination with stem cell therapy.
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Affiliation(s)
- Liyang Yu
- State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, P. R. China.
| | - Haoyong Jin
- Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250100, P. R. China.
- Shandong Key Laboratory of Brain Function Remodeling, Jinan 250117, P. R. China
| | - He Xia
- State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, P. R. China.
| | - Xiaoxiong Wang
- Department of Orthopedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250100, P. R. China
| | - Liang Wang
- State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, P. R. China.
| | - Dezheng Li
- State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, P. R. China.
| | - Jiangli Zhao
- Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250100, P. R. China.
- Shandong Key Laboratory of Brain Function Remodeling, Jinan 250117, P. R. China
| | - Yuanhua Sang
- State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, P. R. China.
| | - Jichuan Qiu
- State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, P. R. China.
| | - Ning Lu
- School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong, 250100, P. R. China.
| | - Hong Liu
- State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, P. R. China.
| | - Ning Yang
- Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250100, P. R. China.
- Shandong Key Laboratory of Brain Function Remodeling, Jinan 250117, P. R. China
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6
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Ait Hamdan Y, El-Mansoury B, Elouali S, Rachmoune K, Belbachir A, Oudadesse H, Rhazi M. A review of chitosan polysaccharides: Neuropharmacological implications and tissue regeneration. Int J Biol Macromol 2024; 279:135356. [PMID: 39244136 DOI: 10.1016/j.ijbiomac.2024.135356] [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: 06/12/2024] [Revised: 08/20/2024] [Accepted: 09/03/2024] [Indexed: 09/09/2024]
Abstract
One of the current challenges in targeting neurological disorders is that many therapeutic molecules cannot cross the blood-brain barrier (BBB), which limits the use of natural molecules in nervous tissue regeneration. Thus, the development of new drugs to effectively treat neurological disorders would be a challenge. Natural resources are well known as a source of several therapeutic agents for the treatment of neurologic disorders. Recently, chitosan (CTS) and its derivatives from arthropod exoskeletons, have attracted much attention as a drug delivery system to transport therapeutic substances across the BBB and thanks to other neuroprotective effects including the participation to the CNS regenerations scaffolds to replicate the extracellular matrix and microenvironment of the body. This review will discuss the place of natural resource therapy in targeting neurological disorders. In particular, it will highlight recent understanding and progress in the applications of CTS as drug delivery systems and their therapeutic effects on these disorders through tissue regeneration, as well as the molecular mechanisms by which they exert these effects.
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Affiliation(s)
- Youssef Ait Hamdan
- Interdisciplinary Laboratory of Research in Bio-Resources, Environment and Materials, Higher Normal School, Cadi Ayyad University, 40000 Marrakech, Morocco; Univ Rennes, CNRS, ISCR-UMR 6226, F-35000 Rennes, France.
| | - Bilal El-Mansoury
- Laboratory of Anthropogenic, Biotechnology and Health, Team physiopathology Nutritional, Neurosciences and Toxicology, Faculty of Sciences, Chouaib Doukkali University, Av. Des facultés, 24000 El Jadida, Morocco
| | - Samia Elouali
- Interdisciplinary Laboratory of Research in Bio-Resources, Environment and Materials, Higher Normal School, Cadi Ayyad University, 40000 Marrakech, Morocco; University of Mons (UMONS) - Laboratory of Polymeric and Composite Materials (LPCM), Center of Innovation and Research in Materials and Polymers (CIRMAP), Place du Parc 20, 7000 Mons, Belgium
| | - Khawla Rachmoune
- Interdisciplinary Laboratory of Research in Bio-Resources, Environment and Materials, Higher Normal School, Cadi Ayyad University, 40000 Marrakech, Morocco; Biotechnology and Biomolecule Engineering Unit, CNESTEN, Rabat, Morocco
| | - Anass Belbachir
- Center for Regenerative Medicine, CHU MOHAMMED VI, Marrakech, Morocco; Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech, Morocco
| | | | - Mohammed Rhazi
- Interdisciplinary Laboratory of Research in Bio-Resources, Environment and Materials, Higher Normal School, Cadi Ayyad University, 40000 Marrakech, Morocco
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Ralph PC, Choi SW, Baek MJ, Lee SJ. Regenerative medicine approaches for the treatment of spinal cord injuries: Progress and challenges. Acta Biomater 2024; 189:57-72. [PMID: 39424019 DOI: 10.1016/j.actbio.2024.10.021] [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: 07/01/2024] [Revised: 10/03/2024] [Accepted: 10/15/2024] [Indexed: 10/21/2024]
Abstract
Spinal cord injury (SCI) is a profound medical condition that significantly hampers motor function, imposing substantial limitations on daily activities and exerting a considerable financial burden on patients and their families. The constrained regenerative capacity of endogenous spinal cord tissue, exacerbated by the inflammatory response following the initial trauma, poses a formidable obstacle to effective therapy. Recent advancements in the field, stem cells, biomaterials, and molecular therapy, show promising outcomes. This review provides a comprehensive analysis of tissue engineering and regenerative medicine approaches for SCI treatment, including cell transplantation, tissue-engineered construct implantation, and other potential therapeutic strategies. Additionally, it sheds light on preclinical animal studies and recent clinical trials incorporating these modalities, providing a glimpse into the evolving landscape of SCI management. STATEMENT OF SIGNIFICANCE: The investigation into spinal cord injury (SCI) treatments focuses on reducing long-term impacts by targeting scar inhibition and enhancing regeneration through stem cells, with or without growth factors. Induced pluripotent stem cells (iPSCs) show promise for autologous use, with clinical trials confirming their safety. Challenges include low cell viability and difficulty in targeted differentiation. Biomaterial scaffolds hold potential for improving cell viability and integration, and extracellular vesicles (EVs) are emerging as a novel therapy. While EV research is in its early stages, stem cell trials demonstrate safety and potential recovery. Advancing tissue engineering approaches with biomaterial scaffolds is crucial for human trials.
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Affiliation(s)
- Patrick C Ralph
- Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, United States
| | - Sung-Woo Choi
- Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, United States; Department of Orthopedic Surgery, Soonchunhyang University Hospital Seoul, Seoul 04401, Republic of Korea
| | - Min Jung Baek
- Department of Obstetrics and Gynecology, CHA University Bundang Medical Center, Seongnam, Gyeonggi-do 13496, Republic of Korea
| | - Sang Jin Lee
- Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, United States.
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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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Wang SH, Wang SR, Luan NN, Sun XQ, Guo YR, Yan YB, Liang SX. Wnt/Ca 2+ pathway inhibits neural differentiation of human dental pulp stem cells in vitro. J Dent Sci 2024; 19:2090-2099. [PMID: 39347028 PMCID: PMC11437312 DOI: 10.1016/j.jds.2024.04.011] [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: 03/09/2024] [Revised: 04/11/2024] [Indexed: 10/01/2024] Open
Abstract
Background/purpose Dental pulp stem cells (DPSCs) have demonstrated significant potential for neuroregeneration. However, a full understanding of the specific mechanism underpinning the neural differentiation of DPSCs is still required. The Wnt signaling is crucial for the development of the embryonic neural system and the maintenance of adult neural homeostasis. This study aimed to investigate the role of the Wnt/Ca2+ pathway in the neural differentiation of human DPSCs (hDPSCs) and its modulation of the Wnt/β-catenin pathway. Materials and methods hDPSCs were cultured and divided into the control group and the neurogenic induction group (Neuro group). The mRNA and protein levels of neurogenic markers, Wnt/Ca2+, and Wnt/β-catenin pathway indicators were determined using Quantitative real-time PCR and Western blotting. After inhibition of the Wnt/Ca2+ pathway using a WNT5A short hairpin RNA (shRNA) plasmid and subsequent neurogenic induction, neurogenic markers and Wnt/β-catenin pathway indicators in the NC-sh-Neuro group and WNT5A-sh-Neuro group were determined using Quantitative real-time PCR and Western blotting. Results Compared with the control group, the expression of the Wnt/Ca2+ pathway indicators (WNT5A, Frizzled 2, calmodulin-dependent protein kinase IIa, and nuclear factor of active T cells 1) decreased in the Neuro group. Conversely, the expression of WNT3A, total β-catenin and active β-catenin in the Wnt/β-catenin pathway increased. Moreover, compared with the NC-sh-Neuro group, the WNT5A-sh-Neuro group exhibited a greater level of mature neural differentiation alongside elevated expression of the Wnt/β-catenin pathway indicators. Conclusion The Wnt/Ca2+ pathway inhibited neural differentiation of hDPSCs and has a negative effect on the Wnt/β-catenin pathway in vitro.
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Affiliation(s)
- Shi-Hua Wang
- Department of Operative Dentistry and Endodontics, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, China
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, China
| | - Shi-Rui Wang
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, China
| | - Na-Na Luan
- Department of Stomatology, Yancheng Third People's Hospital, Yancheng, China
| | - Xiao-Qian Sun
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, China
- Department of Oromaxillofacial-Head and Neck Surgery, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Yi-Ran Guo
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, China
| | - Ying-Bin Yan
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, China
- Department of Oromaxillofacial-Head and Neck Surgery, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Su-Xia Liang
- Department of Operative Dentistry and Endodontics, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, China
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, China
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10
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Haider A, Khan S, Iqbal DN, Khan SU, Haider S, Mohammad K, Mustfa G, Rizwan M, Haider A. Chitosan as a tool for tissue engineering and rehabilitation: Recent developments and future perspectives - A review. Int J Biol Macromol 2024; 278:134172. [PMID: 39111484 DOI: 10.1016/j.ijbiomac.2024.134172] [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: 05/05/2024] [Revised: 07/17/2024] [Accepted: 07/24/2024] [Indexed: 08/17/2024]
Abstract
Chitosan has established itself as a multifunctional and auspicious biomaterial within the domain of tissue engineering, presenting a decade of uninterrupted advancements and novel implementations. This article provides a comprehensive overview of the most recent developments in chitosan-based tissue engineering, focusing on significant progress made in the last ten years. An exploration is conducted of the various techniques utilized in the modification of chitosan and the production of scaffolds, with an analysis of their effects on cellular reactions and tissue regeneration. The investigation focuses on the integration of chitosan with other biomaterials and the addition of bioactive agents to improve their functionalities. Upon careful analysis of the in vitro and in vivo research, it becomes evident that chitosan effectively stimulates cell adhesion, proliferation, and differentiation. Furthermore, we offer valuable perspectives on the dynamic realm of chitosan-based approaches tailored to distinct tissue categories, including nerve, bone, cartilage, and skin. The review concludes with a discussion of prospective developments, with particular attention given to possible directions for additional study, translational implementations, and the utilization of chitosan to tackle existing obstacles in the field of tissue engineering. This extensive examination provides a significant amalgamation of the advancements achieved over the previous decade and directs scholars towards uncharted territories in chitosan-based tissue engineering.
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Affiliation(s)
- Ammar Haider
- Department of Chemistry, The University of Lahore, Lahore 54000, Pakistan
| | - Shabana Khan
- Department of Chemistry, The University of Lahore, Lahore 54000, Pakistan
| | - Dure Najaf Iqbal
- Department of Chemistry, The University of Lahore, Lahore 54000, Pakistan.
| | - Salah Uddin Khan
- Sustainable Energy Technologies Center, College of Engineering, King Saud University, P.O. Box 800, Riyadh 11421, Saudi Arabia; King Salman Center for Disability Research, Riyadh 11614, Saudi Arabia.
| | - Sajjad Haider
- Chemical Engineering Department, College of Engineering, King Saud University, P.O. Box 800, Riyadh 11421, Saudi Arabia
| | - Khaled Mohammad
- Chemical Engineering Department, College of Engineering, King Saud University, P.O. Box 800, Riyadh 11421, Saudi Arabia
| | - Ghulam Mustfa
- Department of Chemistry, The University of Lahore, Lahore 54000, Pakistan
| | - Muhammad Rizwan
- Department of Chemistry, The University of Lahore, Lahore 54000, Pakistan
| | - Adnan Haider
- Department of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, Pakistan
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11
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Zhang S, Yu M, Li M, He M, Xie L, Huo F, Tian W. Notch Signaling Hydrogels Enable Rapid Vascularization and Promote Dental Pulp Tissue Regeneration. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2310285. [PMID: 39013081 PMCID: PMC11425206 DOI: 10.1002/advs.202310285] [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: 12/29/2023] [Revised: 06/07/2024] [Indexed: 07/18/2024]
Abstract
Successful dental pulp regeneration is closely associated with rapid revascularization and angiogenesis, processes driven by the Jagged1(JAG1)/Notch signaling pathway. However, soluble Notch ligands have proven ineffective in activating this pathway. To overcome this limitation, a Notch signaling hydrogel is developed by indirectly immobilizing JAG1, aimed at precisely directing the regeneration of vascularized pulp tissue. This hydrogel displays favorable mechanical properties and biocompatibility. Cultivating dental pulp stem cells (DPSCs) and endothelial cells (ECs) on this hydrogel significantly upregulate Notch target genes and key proangiogenic markers expression. Three-dimensional (3D) culture assays demonstrate Notch signaling hydrogels improve effectiveness by facilitating encapsulated cell differentiation, enhancing their paracrine functions, and promoting capillary lumen formation. Furthermore, it effectively communicates with the Wnt signaling pathway, creating an odontoinductive microenvironment for pulp-dentin complex formation. In vivo studies show that short-term transplantation of the Notch signaling hydrogel accelerates angiogenesis, stabilizes capillary-like structures, and improves cell survival. Long-term transplantation further confirms its capability to promote the formation of pulp-like tissues rich in blood vessels and peripheral nerve-like structures. In conclusion, this study introduces a feasible and effective hydrogel tailored to specifically regulate the JAG1/Notch signaling pathway, showing potential in advancing regenerative strategies for dental pulp tissue.
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Affiliation(s)
- Siyuan Zhang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Oral Regenerative Medicine, Engineering Research Center of Oral Translational Medicine Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Mei Yu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Oral Regenerative Medicine, Engineering Research Center of Oral Translational Medicine Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Maojiao Li
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Oral Regenerative Medicine, Engineering Research Center of Oral Translational Medicine Ministry of Education, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Min He
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Oral Regenerative Medicine, Engineering Research Center of Oral Translational Medicine Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Li Xie
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Oral Regenerative Medicine, Engineering Research Center of Oral Translational Medicine Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Fangjun Huo
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Oral Regenerative Medicine, Engineering Research Center of Oral Translational Medicine Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Weidong Tian
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Oral Regenerative Medicine, Engineering Research Center of Oral Translational Medicine Ministry of Education, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
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12
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Eivazi Zadeh Z, Nour S, Kianersi S, Jonidi Shariatzadeh F, Williams RJ, Nisbet DR, Bruggeman KF. Mining human clinical waste as a rich source of stem cells for neural regeneration. iScience 2024; 27:110307. [PMID: 39156636 PMCID: PMC11326931 DOI: 10.1016/j.isci.2024.110307] [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] [Indexed: 08/20/2024] Open
Abstract
Neural diseases are challenging to treat and are regarded as one of the major causes of disability and morbidity in the world. Stem cells can provide a solution, by offering a mechanism to replace damaged circuitry. However, obtaining sufficient cell sources for neural regeneration remains a significant challenge. In recent years, waste-derived stem(-like) cells (WDS-lCs) extracted from both prenatal and adult clinical waste tissues/products, have gained increasing attention for application in neural tissue repair and remodeling. This often-overlooked pool of cells possesses favorable characteristics; including self-renewal, neural differentiation, secretion of neurogenic factors, cost-effectiveness, and low ethical concerns. Here, we offer a perspective regarding the biological properties, extraction protocols, and preclinical and clinical treatments where prenatal and adult WDS-lCs have been utilized for cell replacement therapy in neural applications, and the challenges involved in optimizing these approaches toward patient led therapies.
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Affiliation(s)
- Zahra Eivazi Zadeh
- Department of Biomedical Engineering, University of Melbourne, Parkville, VIC 3010, Australia
- The Graeme Clark Institute, University of Melbourne, Melbourne, VIC, Australia
| | - Shirin Nour
- Department of Biomedical Engineering, University of Melbourne, Parkville, VIC 3010, Australia
- The Graeme Clark Institute, University of Melbourne, Melbourne, VIC, Australia
- Polymer Science Group, Department of Chemical Engineering, University of Melbourne, Parkville, VIC 3010, Australia
| | - Sogol Kianersi
- Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences, University of Galway, Galway, Ireland
| | | | - Richard J. Williams
- The Graeme Clark Institute, University of Melbourne, Melbourne, VIC, Australia
- iMPACT, School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
| | - David R. Nisbet
- Department of Biomedical Engineering, University of Melbourne, Parkville, VIC 3010, Australia
- The Graeme Clark Institute, University of Melbourne, Melbourne, VIC, Australia
- ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, ANU College of Health & Medicine, Canberra, ACT, Australia
- Research School of Chemistry, ANU College of Science, Canberra, ACT, Australia
- Melbourne Medical School, Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Melbourne, VIC, Australia
- Founder and Scientific Advisory of Nano Status, Building 137, Sullivans Creek Rd, ANU, Acton, Canberra, ACT, Australia
| | - Kiara F. Bruggeman
- Laboratory of Advanced Biomaterials Research, School of Engineering, Australian National University, Canberra, ACT, Australia
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13
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Li K, Chen Z, Chang X, Xue R, Wang H, Guo W. Wnt signaling pathway in spinal cord injury: from mechanisms to potential applications. Front Mol Neurosci 2024; 17:1427054. [PMID: 39114641 PMCID: PMC11303303 DOI: 10.3389/fnmol.2024.1427054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 07/15/2024] [Indexed: 08/10/2024] Open
Abstract
Spinal cord injury (SCI) denotes damage to both the structure and function of the spinal cord, primarily manifesting as sensory and motor deficits caused by disruptions in neural transmission pathways, potentially culminating in irreversible paralysis. Its pathophysiological processes are complex, with numerous molecules and signaling pathways intricately involved. Notably, the pronounced upregulation of the Wnt signaling pathway post-SCI holds promise for neural regeneration and repair. Activation of the Wnt pathway plays a crucial role in neuronal differentiation, axonal regeneration, local neuroinflammatory responses, and cell apoptosis, highlighting its potential as a therapeutic target for treating SCI. However, excessive activation of the Wnt pathway can also lead to negative effects, highlighting the need for further investigation into its applicability and significance in SCI. This paper provides an overview of the latest research advancements in the Wnt signaling pathway in SCI, summarizing the recent progress in treatment strategies associated with the Wnt pathway and analyzing their advantages and disadvantages. Additionally, we offer insights into the clinical application of the Wnt signaling pathway in SCI, along with prospective avenues for future research direction.
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Affiliation(s)
| | | | | | | | - Huaibo Wang
- Department of Spine Surgery, The Second Hospital Affiliated to Guangdong Medical University, Zhanjiang, China
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14
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Jenkner S, Clark JM, Gronthos S, O’Hare Doig RL. Molars to Medicine: A Focused Review on the Pre-Clinical Investigation and Treatment of Secondary Degeneration following Spinal Cord Injury Using Dental Stem Cells. Cells 2024; 13:817. [PMID: 38786039 PMCID: PMC11119219 DOI: 10.3390/cells13100817] [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: 04/01/2024] [Revised: 05/01/2024] [Accepted: 05/07/2024] [Indexed: 05/25/2024] Open
Abstract
Spinal cord injury (SCI) can result in the permanent loss of mobility, sensation, and autonomic function. Secondary degeneration after SCI both initiates and propagates a hostile microenvironment that is resistant to natural repair mechanisms. Consequently, exogenous stem cells have been investigated as a potential therapy for repairing and recovering damaged cells after SCI and other CNS disorders. This focused review highlights the contributions of mesenchymal (MSCs) and dental stem cells (DSCs) in attenuating various secondary injury sequelae through paracrine and cell-to-cell communication mechanisms following SCI and other types of neurotrauma. These mechanistic events include vascular dysfunction, oxidative stress, excitotoxicity, apoptosis and cell loss, neuroinflammation, and structural deficits. The review of studies that directly compare MSC and DSC capabilities also reveals the superior capabilities of DSC in reducing the effects of secondary injury and promoting a favorable microenvironment conducive to repair and regeneration. This review concludes with a discussion of the current limitations and proposes improvements in the future assessment of stem cell therapy through the reporting of the effects of DSC viability and DSC efficacy in attenuating secondary damage after SCI.
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Affiliation(s)
- Sandra Jenkner
- School of Biomedicine, Faculty of Health and Medical Sciences, University of Adelaide, North Terrace, Adelaide 5000, Australia; (S.J.); (S.G.)
- Neil Sachse Centre for Spinal Cord Research, Lifelong Health Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide 5000, Australia;
| | - Jillian Mary Clark
- Neil Sachse Centre for Spinal Cord Research, Lifelong Health Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide 5000, Australia;
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, North Terrace, Adelaide 5000, Australia
| | - Stan Gronthos
- School of Biomedicine, Faculty of Health and Medical Sciences, University of Adelaide, North Terrace, Adelaide 5000, Australia; (S.J.); (S.G.)
- Mesenchymal Stem Cell Laboratory, Precision Medicine Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide 5000, Australia
| | - Ryan Louis O’Hare Doig
- Neil Sachse Centre for Spinal Cord Research, Lifelong Health Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide 5000, Australia;
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, North Terrace, Adelaide 5000, Australia
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Manero-Roig I, Polo Y, Pardo-Rodríguez B, Luzuriaga J, Basanta-Torres R, Martín-Aragón D, Romayor I, Martín-Colomo S, Márquez J, Gomez-Santos L, Lanore F, Humeau Y, Ibarretxe G, Eguizabal C, Larrañaga A, Pineda JR. Intracranial graft of bioresorbable polymer scaffolds loaded with human Dental Pulp Stem Cells in stab wound murine injury model. Methods Cell Biol 2024; 188:237-254. [PMID: 38880526 DOI: 10.1016/bs.mcb.2024.03.011] [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] [Indexed: 06/18/2024]
Abstract
The prevalence of central nervous system (CNS) dysfunction as a result of disease or trauma remains a clinically unsolved problem which is raising increased awareness in our aging society. Human Dental Pulp Stem Cells (hDPSCs) are excellent candidates to be used in tissue engineering and regenerative therapies of the CNS due to their neural differentiation ability and lack of tumorigenicity. Accordingly, they have been successfully used in animal models of spinal cord injury, stroke and peripheral neuropathies. The ideal therapy in brain injury should combine strategies aiming to protect the damaged lesion and, at the same time, accelerate brain tissue regeneration, thus promoting fast recovery while minimizing side or long-term effects. The use of bioresorbable nanopatterned poly(lactide-co-ɛ-caprolactone) (PLCL) polymeric scaffolds as hDPCSs carriers can represent an advantage for tissue regeneration. In this chapter, we describe the surgical procedures to implant functionalized bioresorbable scaffolds loaded with hDPSCs to improve the brain lesion microenvironment in an intracranial stab wound injury model severing the rostral migratory stream (RMS) that connects the brain subventricular zone (SVZ) and the olfactory bulb in nude mice. Additionally, we also describe the technical steps after animal sacrifice for histological tissue observation and characterization.
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Affiliation(s)
- Irene Manero-Roig
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain; University of Bordeaux, CNRS, IINS, UMR 5297, Bordeaux, France
| | - Yurena Polo
- Polimerbio SL, Donostia-San Sebastián, Spain
| | - Beatriz Pardo-Rodríguez
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
| | - Jon Luzuriaga
- Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
| | - Ruth Basanta-Torres
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
| | - Daniel Martín-Aragón
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
| | - Irene Romayor
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain; Cell Therapy, Stem Cells and Tissues Group, Biobizkaia Health Research Institute, Barakaldo, Spain; Advanced Therapies Unit, Basque Center for Blood Transfusion and Human Tissues, Bizkaia, Spain
| | - Sara Martín-Colomo
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain; Group of Science and Engineering of Polymeric Biomaterials (ZIBIO Group), Department of Mining, Metallurgy Engineering and Materials Science, POLYMAT, University of the Basque Country (UPV/EHU), Bilbao, Spain
| | - Joana Márquez
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
| | - Laura Gomez-Santos
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
| | - Frédéric Lanore
- University of Bordeaux, CNRS, IINS, UMR 5297, Bordeaux, France
| | - Yann Humeau
- University of Bordeaux, CNRS, IINS, UMR 5297, Bordeaux, France
| | - Gaskon Ibarretxe
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain.
| | - Cristina Eguizabal
- Cell Therapy, Stem Cells and Tissues Group, Biobizkaia Health Research Institute, Barakaldo, Spain; Advanced Therapies Unit, Basque Center for Blood Transfusion and Human Tissues, Bizkaia, Spain.
| | - Aitor Larrañaga
- Group of Science and Engineering of Polymeric Biomaterials (ZIBIO Group), Department of Mining, Metallurgy Engineering and Materials Science, POLYMAT, University of the Basque Country (UPV/EHU), Bilbao, Spain.
| | - Jose Ramon Pineda
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain; Achucarro Basque Center for Neuroscience Fundazioa, Leioa, Spain.
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16
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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] [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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Ye L, Yu Z, He L, Yuan J, Zhang X, Li L, Huang X, Ma Y, Zhang L. KAT2A-mediated succinylation modification of notch1 promotes the proliferation and differentiation of dental pulp stem cells by activating notch pathway. BMC Oral Health 2024; 24:407. [PMID: 38556862 PMCID: PMC10981825 DOI: 10.1186/s12903-024-03951-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 01/29/2024] [Indexed: 04/02/2024] Open
Abstract
BACKGROUND Dental pulp stem cells (DPSCs) are a kind of undifferentiated dental mesenchymal stem cells with strong self-renewal ability and multi-differentiation potential. This study aimed to investigate the regulatory functions of succinylation modification in DPSCs. METHODS DPSCs were isolated from the dental pulp collected from healthy subjects, and then stem cell surface markers were identified using flow cytometry. The osteogenic differentiation ability of DPSCs was verified by alkaline phosphatase (ALP) and alizarin red staining methods, while adipogenic differentiation was detected by oil red O staining. Meanwhile, the mRNA of two desuccinylases (SIRT5 and SIRT7) and three succinylases (KAT2A, KAT3B, and CPT1A) in DPSCs before and after mineralization induction were detected using quantitative real-time PCR. The cell cycle was measured by flow cytometry, and the expression of bone-specific genes, including COL1a1 and Runx2 were evaluated by western blotting and were combined for the proliferation and differentiation of DPSCs. Co-immunoprecipitation (co-IP) and immunofluorescence were combined to verify the binding relationship between proteins. RESULTS The specific markers of mesenchymal stem cells were highly expressed in DPSCs, while the osteogenic differentiation ability of isolated DPSCs was confirmed via ALP and alizarin red staining. Similarly, the oil red O staining also verified the adipogenic differentiation ability of DPSCs. The levels of KAT2A were found to be significantly upregulated in mineralization induction, which significantly decreased the ratio of G0/G1 phase and increased S phase cells; converse results regarding cell cycle distribution were obtained when KAT2A was inhibited. Moreover, overexpression of KAT2A promoted the differentiation of DPSCs, while its inhibition exerted the opposite effect. The elevated KAT2A was found to activate the Notch1 signaling pathway, which succinylated Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. The co-IP results showed that KAT2A and Notch1 were endogenously bound to each other, while inhibition of Notch1 reversed the effects of KAT2A overexpression on the DPSCs proliferation and differentiation. CONCLUSION KAT2A interacted directly with Notch1, succinylating the Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. Similarly, KAT2A-mediated succinylation modification of Notch1 promotes the DPSCs proliferation and differentiation, suggesting that targeting KAT2A and Notch1 may contribute to tooth regeneration.
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Affiliation(s)
- Longwei Ye
- Department of Oral Health and Prevention, The First Affiliated Hospital of Harbin Medical University. Harbin Medical University, School of Stomatology, No.143 Yiman Street, Nangang District, Harbin City, 150001, Heilongjiang Province, China
| | - Zeqin Yu
- Department of Oral Health and Prevention, The First Affiliated Hospital of Harbin Medical University. Harbin Medical University, School of Stomatology, No.143 Yiman Street, Nangang District, Harbin City, 150001, Heilongjiang Province, China
| | - Lin He
- Department of Stomatology, Heilongjiang Province Hospital, Harbin City, 150081, Heilongjiang Province, China
| | - Jie Yuan
- Department of Oral Health and Prevention, The First Affiliated Hospital of Harbin Medical University. Harbin Medical University, School of Stomatology, No.143 Yiman Street, Nangang District, Harbin City, 150001, Heilongjiang Province, China
| | - Xiaodan Zhang
- Department of Oral Health and Prevention, The First Affiliated Hospital of Harbin Medical University. Harbin Medical University, School of Stomatology, No.143 Yiman Street, Nangang District, Harbin City, 150001, Heilongjiang Province, China
| | - Lei Li
- Department of Oral Health and Prevention, The First Affiliated Hospital of Harbin Medical University. Harbin Medical University, School of Stomatology, No.143 Yiman Street, Nangang District, Harbin City, 150001, Heilongjiang Province, China
| | - Xin Huang
- Department of Oral Health and Prevention, The First Affiliated Hospital of Harbin Medical University. Harbin Medical University, School of Stomatology, No.143 Yiman Street, Nangang District, Harbin City, 150001, Heilongjiang Province, China
| | - Yanyan Ma
- Pharmaceutical Department, The First Affiliated Hospital of Harbin Medical University, Harbin City, 150001, Heilongjiang Province, China
| | - Lei Zhang
- Department of Oral Health and Prevention, The First Affiliated Hospital of Harbin Medical University. Harbin Medical University, School of Stomatology, No.143 Yiman Street, Nangang District, Harbin City, 150001, Heilongjiang Province, China.
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Yang Y, Fan R, Li H, Chen H, Gong H, Guo G. Polysaccharides as a promising platform for the treatment of spinal cord injury: A review. Carbohydr Polym 2024; 327:121672. [PMID: 38171685 DOI: 10.1016/j.carbpol.2023.121672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 11/20/2023] [Accepted: 12/05/2023] [Indexed: 01/05/2024]
Abstract
Spinal cord injury is incurable and often results in irreversible damage to motor function and autonomic sensory abilities. To enhance the effectiveness of therapeutic substances such as cells, growth factors, drugs, and nucleic acids for treating spinal cord injuries, as well as to reduce the toxic side effects of chemical reagents, polysaccharides have been gained attention due to their immunomodulatory properties and the biocompatibility and biodegradability of polysaccharide scaffolds. Polysaccharides hold potential as drug delivery systems in treating spinal cord injuries. This article aims to present an extensive evaluation of the potential applications of polysaccharide materials in scaffold construction, drug delivery, and immunomodulation over the past five years so that offering new directions and opportunities for the treatment of spinal cord injuries.
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Affiliation(s)
- Yuanli Yang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Rangrang Fan
- Department of Neurosurgery and Institute of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Hui Li
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Haifeng Chen
- Department of Neurosurgery and Institute of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Hanlin Gong
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
| | - Gang Guo
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
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19
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Zawadzka-Knefel A, Rusak A, Mrozowska M, Machałowski T, Żak A, Haczkiewicz-Leśniak K, Kulus M, Kuropka P, Podhorska-Okołów M, Skośkiewicz-Malinowska K. Chitin scaffolds derived from the marine demosponge Aplysina fistularis stimulate the differentiation of dental pulp stem cells. Front Bioeng Biotechnol 2023; 11:1254506. [PMID: 38033818 PMCID: PMC10682193 DOI: 10.3389/fbioe.2023.1254506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 10/24/2023] [Indexed: 12/02/2023] Open
Abstract
The use of stem cells for tissue regeneration is a prominent trend in regenerative medicine and tissue engineering. In particular, dental pulp stem cells (DPSCs) have garnered considerable attention. When exposed to specific conditions, DPSCs have the ability to differentiate into osteoblasts and odontoblasts. Scaffolds are critical for cell differentiation because they replicate the 3D microenvironment of the niche and enhance cell adhesion, migration, and differentiation. The purpose of this study is to present the biological responses of human DPSCs to a purified 3D chitin scaffold derived from the marine demosponge Aplysina fistularis and modified with hydroxyapatite (HAp). Responses examined included proliferation, adhesion, and differentiation. The control culture consisted of the human osteoblast cell line, hFOB 1.19. Electron microscopy was used to examine the ultrastructure of the cells (transmission electron microscopy) and the surface of the scaffold (scanning electron microscopy). Cell adhesion to the scaffolds was determined by neutral red and crystal violet staining methods. An alkaline phosphatase (ALP) assay was used for assessing osteoblast/odontoblast differentiation. We evaluated the expression of osteogenic marker genes by performing ddPCR for ALP, RUNX2, and SPP1 mRNA expression levels. The results show that the chitin biomaterial provides a favorable environment for DPSC and hFOB 1.19 cell adhesion and supports both cell proliferation and differentiation. The chitin scaffold, especially with HAp modification, isolated from A. fistularis can make a significant contribution to tissue engineering and regenerative medicine.
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Affiliation(s)
- Anna Zawadzka-Knefel
- Department of Conservative Dentistry with Endodontics, Wroclaw Medical University, Wroclaw, Poland
| | - Agnieszka Rusak
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Monika Mrozowska
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Tomasz Machałowski
- Institute of Chemical Technology and Engineering, Faculty of Chemical Technology, Poznan University of Technology, Poznan, Poland
| | - Andrzej Żak
- Electron Microscopy Laboratory, Faculty of Chemistry, Wroclaw University of Science and Technology, Wroclaw, Poland
| | | | - Michał Kulus
- Division of Ultrastructural Research, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Piotr Kuropka
- Division of Histology and Embryology, Department of Biostructure and Animal Physiology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland
| | - Marzenna Podhorska-Okołów
- Division of Ultrastructural Research, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
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20
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Rawiwet V, Vijitruth R, Thonabulsombat C, Vongsavan K, Sritanaudomchai H. Evaluation of the Efficacy of Human Dental Pulp Stem Cell Transplantation in Sprague-Dawley Rats with Sensorial Neural Hearing Loss. Eur J Dent 2023; 17:1207-1214. [PMID: 36716786 PMCID: PMC10756831 DOI: 10.1055/s-0043-1761190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
OBJECTIVES The purpose of the present study was to evaluate the efficacy of spiral ganglion neuron (SGN) regeneration after dental pulp stem cell (DPSC) transplantation in a rat sensorineural hearing loss (HL) model. MATERIALS AND METHODS Sham or experimental HL was induced in adult Sprague-Dawley rats by cochlear round window surgery. An HL rat model was established with a single 10 mM ouabain intratympanic injection. After 7 days, the rats received DPSCs, stem cells from human exfoliated deciduous teeth (SHED), or culture medium in the sutural area to establish four groups: sham, HL-DPSC, HL-SHED, and HL-medium. Histological analyses were performed at 4, 7, and 10 weeks after transplantation, and the number of SGNs, specific SGN protein expression, and the function of SGNs were evaluated. STATISTICAL ANALYSIS Data were statistically by MS Excel and SPSS v.15.0. Intergroup level of significance was determined via a one-way analysis of variance and Duncan's multiple range test with 95% confidence intervals. RESULTS New SGN formation was observed in the HL-DPSC and HL-SHED rat groups. The number of SGNs was significantly higher in the HL-DPSC and HL-SHED groups than in the HL-medium group over 4 to 10-week survival period. HL-DPSC rats exhibited higher SGN density compared with that in HL-SHED group, which was statistically significant at week 10. The regenerated SGNs expressed cochlear wiring regulator GATA-binding-protein 3. Moreover, the SGNs from the HL-DPSC group also exhibited a higher expression of synaptic vesicle protein and regulated action potential-dependent neurotransmitter release compared with SGNs from the HL-SHED group. CONCLUSIONS Our findings suggest that DPSCs and SHED repair and regenerate SGNs in rat HL model. Dental pulp stem cells represent a promising treatment strategy for restoring damage to the sensory circuits associated with deafness.
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Affiliation(s)
- Visut Rawiwet
- Central Animal Facility, Faculty of Science, Mahidol University (MUSC-CAF), Bangkok, Thailand
| | | | | | - Kutkao Vongsavan
- Department of Pediatric Dentistry, Faculty of Dentistry, Mahidol University, Bangkok, Thailand
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21
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Piperigkou Z, Bainantzou D, Makri N, Papachristou E, Mantsou A, Choli-Papadopoulou T, Theocharis AD, Karamanos NK. Enhancement of mesenchymal stem cells' chondrogenic potential by type II collagen-based bioscaffolds. Mol Biol Rep 2023; 50:5125-5135. [PMID: 37118382 PMCID: PMC10209287 DOI: 10.1007/s11033-023-08461-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 04/12/2023] [Indexed: 04/30/2023]
Abstract
BACKGROUND Osteoarthritis (OA) is a common degenerative chronic disease accounting for physical pain, tissue stiffness and mobility restriction. Current therapeutic approaches fail to prevent the progression of the disease considering the limited knowledge on OA pathobiology. During OA progression, the extracellular matrix (ECM) of the cartilage is aberrantly remodeled by chondrocytes. Chondrocytes, being the main cell population of the cartilage, participate in cartilage regeneration process. To this end, modern tissue engineering strategies involve the recruitment of mesenchymal stem cells (MSCs) due to their regenerative capacity as to promote chondrocyte self-regeneration. METHODS AND RESULTS In the present study, we evaluated the role of type II collagen, as the main matrix macromolecule in the cartilage matrix, to promote chondrogenic differentiation in two MSC in vitro culture systems. The chondrogenic differentiation of human Wharton's jelly- and dental pulp-derived MSCs was investigated over a 24-day culture period on type II collagen coating to improve the binding affinity of MSCs. Functional assays, demonstrated that type II collagen promoted chondrogenic differentiation in both MSCs tested, which was confirmed through gene and protein analysis of major chondrogenic markers. CONCLUSIONS Our data support that type II collagen contributes as a natural bioscaffold enhancing chondrogenesis in both MSC models, thus enhancing the commitment of MSC-based therapeutic approaches in regenerative medicine to target OA and bring therapy closer to the clinical use.
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Affiliation(s)
- Zoi Piperigkou
- Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece
- Foundation for Research and Technology-Hellas (FORTH)/Institute of Chemical Engineering Sciences (ICE-HT), Patras, Greece
| | - Dimitra Bainantzou
- Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece
| | - Nadia Makri
- Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece
| | - Eleni Papachristou
- Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Aglaia Mantsou
- Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Theodora Choli-Papadopoulou
- Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Achilleas D Theocharis
- Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.
| | - Nikos K Karamanos
- Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.
- Foundation for Research and Technology-Hellas (FORTH)/Institute of Chemical Engineering Sciences (ICE-HT), Patras, Greece.
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22
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Pourkhodadad S, Hosseinkazemi H, Bonakdar S, Nekounam H. Biomimetic engineered approaches for neural tissue engineering: Spinal cord injury. J Biomed Mater Res B Appl Biomater 2023; 111:701-716. [PMID: 36214332 DOI: 10.1002/jbm.b.35171] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 07/16/2022] [Accepted: 09/03/2022] [Indexed: 01/21/2023]
Abstract
The healing process for spinal cord injuries is complex and presents many challenges. Current advances in nerve regeneration are based on promising tissue engineering techniques, However, the chances of success depend on better mimicking the extracellular matrix (ECM) of neural tissue and better supporting neurons in a three-dimensional environment. The ECM provides excellent biological conditions, including desirable morphological features, electrical conductivity, and chemical compositions for neuron attachment, proliferation and function. This review outlines the rationale for developing a construct for neuron regrowth in spinal cord injury using appropriate biomaterials and scaffolding techniques.
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Affiliation(s)
| | - Hessam Hosseinkazemi
- Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran
| | - Shahin Bonakdar
- National Cell Bank Department, Pasteur Institute of Iran, Tehran, Iran
| | - Houra Nekounam
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
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23
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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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24
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Suzuki H, Imajo Y, Funaba M, Ikeda H, Nishida N, Sakai T. Current Concepts of Biomaterial Scaffolds and Regenerative Therapy for Spinal Cord Injury. Int J Mol Sci 2023; 24:ijms24032528. [PMID: 36768846 PMCID: PMC9917245 DOI: 10.3390/ijms24032528] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/05/2023] [Accepted: 01/11/2023] [Indexed: 02/03/2023] Open
Abstract
Spinal cord injury (SCI) is a catastrophic condition associated with significant neurological deficit and social and financial burdens. It is currently being managed symptomatically, with no real therapeutic strategies available. In recent years, a number of innovative regenerative strategies have emerged and have been continuously investigated in preclinical research and clinical trials. In the near future, several more are expected to come down the translational pipeline. Among ongoing and completed trials are those reporting the use of biomaterial scaffolds. The advancements in biomaterial technology, combined with stem cell therapy or other regenerative therapy, can now accelerate the progress of promising novel therapeutic strategies from bench to bedside. Various types of approaches to regeneration therapy for SCI have been combined with the use of supportive biomaterial scaffolds as a drug and cell delivery system to facilitate favorable cell-material interactions and the supportive effect of neuroprotection. In this review, we summarize some of the most recent insights of preclinical and clinical studies using biomaterial scaffolds in regenerative therapy for SCI and summarized the biomaterial strategies for treatment with simplified results data. One hundred and sixty-eight articles were selected in the present review, in which we focused on biomaterial scaffolds. We conducted our search of articles using PubMed and Medline, a medical database. We used a combination of "Spinal cord injury" and ["Biomaterial", or "Scaffold"] as search terms and searched articles published up until 30 April 2022. Successful future therapies will require these biomaterial scaffolds and other synergistic approaches to address the persistent barriers to regeneration, including glial scarring, the loss of a structural framework, and biocompatibility. This database could serve as a benchmark to progress in future clinical trials for SCI using biomaterial scaffolds.
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25
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Mattei V, Delle Monache S. Dental Pulp Stem Cells (DPSCs) and Tissue Regeneration: Mechanisms Mediated by Direct, Paracrine, or Autocrine Effects. Biomedicines 2023; 11:biomedicines11020386. [PMID: 36830923 PMCID: PMC9953448 DOI: 10.3390/biomedicines11020386] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 01/18/2023] [Indexed: 01/31/2023] Open
Abstract
Among mesenchymal stem cells, dental pulp stem cells (DPSCs) were discovered most recently [...].
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Affiliation(s)
- Vincenzo Mattei
- Biomedicine and Advanced Technologies Rieti Center, Sabina Universitas, 02100 Rieti, Italy
- Correspondence: (V.M.); (S.D.M.)
| | - Simona Delle Monache
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
- Correspondence: (V.M.); (S.D.M.)
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26
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Neural Regeneration in Regenerative Endodontic Treatment: An Overview and Current Trends. Int J Mol Sci 2022; 23:ijms232415492. [PMID: 36555133 PMCID: PMC9779866 DOI: 10.3390/ijms232415492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 11/24/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022] Open
Abstract
Pulpal and periapical diseases are the most common dental diseases. The traditional treatment is root canal therapy, which achieves satisfactory therapeutic outcomes-especially for mature permanent teeth. Apexification, pulpotomy, and pulp revascularization are common techniques used for immature permanent teeth to accelerate the development of the root. However, there are obstacles to achieving functional pulp regeneration. Recently, two methods have been proposed based on tissue engineering: stem cell transplantation, and cell homing. One of the goals of functional pulp regeneration is to achieve innervation. Nerves play a vital role in dentin formation, nutrition, sensation, and defense in the pulp. Successful neural regeneration faces tough challenges in both animal studies and clinical trials. Investigation of the regeneration and repair of the nerves in the pulp has become a serious undertaking. In this review, we summarize the current understanding of the key stem cells, signaling molecules, and biomaterials that could promote neural regeneration as part of pulp regeneration. We also discuss the challenges in preclinical or clinical neural regeneration applications to guide deep research in the future.
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27
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Dieterle MP, Gross T, Steinberg T, Tomakidi P, Becker K, Vach K, Kremer K, Proksch S. Characterization of a Stemness-Optimized Purification Method for Human Dental-Pulp Stem Cells: An Approach to Standardization. Cells 2022; 11:cells11203204. [PMID: 36291072 PMCID: PMC9600643 DOI: 10.3390/cells11203204] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 10/06/2022] [Accepted: 10/09/2022] [Indexed: 11/16/2022] Open
Abstract
Human dental pulp stem cells (hDPSCs) are promising for oral/craniofacial regeneration, but their purification and characterization is not yet standardized. hDPSCs from three donors were purified by magnetic activated cell sorting (MACS)-assisted STRO-1-positive cell enrichment (+), colony derivation (c), or a combination of both (c/+). Immunophenotype, clonogenicity, stemness marker expression, senescence, and proliferation were analyzed. Multilineage differentiation was assessed by qPCR, immunohistochemistry, and extracellular matrix mineralization. To confirm the credibility of the results, repeated measures analysis and post hoc p-value adjustment were applied. All hDPSC fractions expressed STRO-1 and were similar for several surface markers, while their clonogenicity and expression of CD10/44/105/146, and 166 varied with the purification method. (+) cells proliferated significantly faster than (c/+), while (c) showed the highest increase in metabolic activity. Colony formation was most efficient in (+) cells, which also exhibited the lowest cellular senescence. All hDPSCs produced mineralized extracellular matrix. Regarding osteogenic induction, (c/+) revealed a significant increase in mRNA expression of COL5A1 and COL6A1, while osteogenic marker genes were detected at varying levels. (c/+) were the only population missing BDNF gene transcription increase during neurogenic induction. All hDPSCs were able to differentiate into chondrocytes. In summary, the three hDPSCs populations showed differences in phenotype, stemness, proliferation, and differentiation capacity. The data suggest that STRO-1-positive cell enrichment is the optimal choice for hDPSCs purification to maintain hDPSCs stemness. Furthermore, an (immuno) phenotypic characterization is the minimum requirement for quality control in hDPSCs studies.
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Affiliation(s)
- Martin Philipp Dieterle
- Division of Oral Biotechnology, Center for Dental Medicine, Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany
| | - Tara Gross
- Department of Operative Dentistry and Periodontology, Centre for Dental Medicine Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79106 Freiburg, Germany
- G.E.R.N. Center for Tissue Replacement, Regeneration & Neogenesis, Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79108 Freiburg, Germany
| | - Thorsten Steinberg
- Division of Oral Biotechnology, Center for Dental Medicine, Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany
- Correspondence: ; Tel.: +49-761-27047460
| | - Pascal Tomakidi
- Division of Oral Biotechnology, Center for Dental Medicine, Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany
| | - Kathrin Becker
- Department of Operative Dentistry and Periodontology, Centre for Dental Medicine Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79106 Freiburg, Germany
| | - Kirstin Vach
- Institute of Medical Biometry and Statistics, Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79104 Freiburg, Germany
| | - Katrin Kremer
- Department of Oral and Maxillofacial Surgery, Center for Dental Medicine, Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79106 Freiburg, Germany
| | - Susanne Proksch
- Department of Operative Dentistry and Periodontology, Centre for Dental Medicine Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79106 Freiburg, Germany
- G.E.R.N. Center for Tissue Replacement, Regeneration & Neogenesis, Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79108 Freiburg, Germany
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28
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Pourhadi M, Zali H, Ghasemi R, Vafaei-Nezhad S. Promising Role of Oral Cavity Mesenchymal Stem Cell-Derived Extracellular Vesicles in Neurodegenerative Diseases. Mol Neurobiol 2022; 59:6125-6140. [PMID: 35867205 DOI: 10.1007/s12035-022-02951-y] [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: 09/21/2021] [Accepted: 06/28/2022] [Indexed: 10/17/2022]
Abstract
Mesenchymal stem cells (MSCs) and mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been regarded as the beneficial and available tools to treat various hereditary, multifactorial, acute, and chronic diseases. Mesenchymal stem cells can be extracted from numerous sources for clinical purposes while oral cavity-derived mesenchymal stem cells seem to be more effective in neuroregeneration than other sources due to their similar embryonic origins to neuronal tissues. In various studies and different neurodegenerative diseases (NDs), oral cavity mesenchymal stem cells have been applied to prove their promising capacities in disease improvement. Moreover, oral cavity mesenchymal stem cells' secretion is regarded as a novel and practical approach to neuroregeneration; hence, extracellular vesicles (EVs), especially exosomes, may provide promising results to improve CNS defects. This review article focuses on how oral cavity-derived stem cells and their extracellular vesicles can improve neurodegenerative conditions and tries to show which molecules are involved in the recovery process.
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Affiliation(s)
- Masoumeh Pourhadi
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hakimeh Zali
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Rasoul Ghasemi
- Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeed Vafaei-Nezhad
- Cellular & Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.,Department of Anatomical Sciences, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
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29
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Zou J, Mao J, Shi X. Influencing factors of pulp-dentin complex regeneration and related biological strategies. Zhejiang Da Xue Xue Bao Yi Xue Ban 2022; 51:350-361. [PMID: 36207838 PMCID: PMC9511472 DOI: 10.3724/zdxbyxb-2022-0046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 04/12/2022] [Indexed: 06/16/2023]
Abstract
Regenerative endodontic therapy (RET) utilizing tissue engineering approach can promote the regeneration of pulp-dentin complex to restore pulp vascularization, neuralization, immune function and tubular dentin, therefore the regenerated pulp-dentin complex will have normal function. Multiple factors may significantly affect the efficacy of RET, including stem cells, biosignaling molecules and biomaterial scaffolds. Stem cells derived from dental tissues (such as dental pulp stem cells) exhibit certain advantages in RET. Combined application of multiple signaling molecules and activation of signal transduction pathways such as Wnt/β-catenin and BMP/Smad play pivotal roles in enhancing the potential of stem cell migration, proliferation, odontoblastic differentiation, and nerve and blood vessel regeneration. Biomaterials suitable for RET include naturally-derived materials and artificially synthetic materials. Artificially synthetic materials should imitate natural tissues for biomimetic modification in order to realize the temporal and spatial regulation of pulp-dentin complex regeneration. The realization of pulp-dentin complex regeneration depends on two strategies: stem cell transplantation and stem cell homing. Stem cell homing strategy does not require the isolation and culture of stem cells in vitro, so is better for clinical application. However, in order to achieve the true regeneration of pulp-dentin complex, problems related to improving the success rate of stem cell homing and promoting their proliferation and differentiation need to be solved. This article reviews the influencing factors of pulp-dentin complex regeneration and related biological strategies, and discusses the future research direction of RET, to provide reference for clinical translation and application of RET.
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Affiliation(s)
- Jielin Zou
- 1. Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- 2. School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- 3. Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Jing Mao
- 1. Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- 2. School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- 3. Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Xin Shi
- 1. Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- 2. School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- 3. Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
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30
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Lv Z, Dong C, Zhang T, Zhang S. Hydrogels in Spinal Cord Injury Repair: A Review. Front Bioeng Biotechnol 2022; 10:931800. [PMID: 35800332 PMCID: PMC9253563 DOI: 10.3389/fbioe.2022.931800] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 05/26/2022] [Indexed: 12/18/2022] Open
Abstract
Traffic accidents and falling objects are responsible for most spinal cord injuries (SCIs). SCI is characterized by high disability and tends to occur among the young, seriously affecting patients' lives and quality of life. The key aims of repairing SCI include preventing secondary nerve injury, inhibiting glial scarring and inflammatory response, and promoting nerve regeneration. Hydrogels have good biocompatibility and degradability, low immunogenicity, and easy-to-adjust mechanical properties. While providing structural scaffolds for tissues, hydrogels can also be used as slow-release carriers in neural tissue engineering to promote cell proliferation, migration, and differentiation, as well as accelerate the repair of damaged tissue. This review discusses the characteristics of hydrogels and their advantages as delivery vehicles, as well as expounds on the progress made in hydrogel therapy (alone or combined with cells and molecules) to repair SCI. In addition, we discuss the prospects of hydrogels in clinical research and provide new ideas for the treatment of SCI.
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Affiliation(s)
- Zhenshan Lv
- The Department of Spinal Surgery, 1st Hospital, Jilin University, Jilin Engineering Research Center for Spine and Spine Cord Injury, Changchun, China
| | - Chao Dong
- Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Tianjiao Zhang
- Medical Insurance Management Department, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Shaokun Zhang
- The Department of Spinal Surgery, 1st Hospital, Jilin University, Jilin Engineering Research Center for Spine and Spine Cord Injury, Changchun, China
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Gao Y, Tian Z, Liu Q, Wang T, Ban LK, Lee HHC, Umezawa A, Almansour AI, Arumugam N, Kumar RS, Ye Q, Higuchi A, Chen H, Sung TC. Neuronal Cell Differentiation of Human Dental Pulp Stem Cells on Synthetic Polymeric Surfaces Coated With ECM Proteins. Front Cell Dev Biol 2022; 10:893241. [PMID: 35774224 PMCID: PMC9237518 DOI: 10.3389/fcell.2022.893241] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 04/01/2022] [Indexed: 01/09/2023] Open
Abstract
Stem cells serve as an ideal source of tissue regeneration therapy because of their high stemness properties and regenerative activities. Mesenchymal stem cells (MSCs) are considered an excellent source of stem cell therapy because MSCs can be easily obtained without ethical concern and can differentiate into most types of cells in the human body. We prepared cell culture materials combined with synthetic polymeric materials of poly-N-isopropylacrylamide-co-butyl acrylate (PN) and extracellular matrix proteins to investigate the effect of cell culture biomaterials on the differentiation of dental pulp stem cells (DPSCs) into neuronal cells. The DPSCs cultured on poly-L-ornithine (PLO)-coated (TPS-PLO) plates and PLO and PN-coated (TPS-PLO-PN) plates showed excellent neuronal marker (βIII-tubulin and nestin) expression and the highest expansion rate among the culture plates investigated in this study. This result suggests that the TPS-PLO and TPS-PN-PLO plates maintained stable DPSCs proliferation and had good capabilities of differentiating into neuronal cells. TPS-PLO and TPS-PN-PLO plates may have high potentials as cell culture biomaterials for the differentiation of MSCs into several neural cells, such as cells in the central nervous system, retinal cells, retinal organoids and oligodendrocytes, which will expand the sources of cells for stem cell therapies in the future.
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Affiliation(s)
- Yan Gao
- School of Biomedical Engineering, The Eye Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China
| | - Zeyu Tian
- School of Biomedical Engineering, The Eye Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China
| | - Qian Liu
- School of Biomedical Engineering, The Eye Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China
| | - Ting Wang
- School of Biomedical Engineering, The Eye Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China
| | - Lee-Kiat Ban
- Department of Surgery, Hsinchu Cathay General Hospital, Hsinchu, Taiwan
| | - Henry Hsin-Chung Lee
- Department of Surgery, Hsinchu Cathay General Hospital, Hsinchu, Taiwan
- Graduate Institute of Translational and Interdisciplinary Medicine, National Central University, Taoyuan, Taiwan
| | - Akihiro Umezawa
- Department of Reproduction, National Center for Child Health and Development, Tokyo, Japan
| | | | - Natarajan Arumugam
- Department of Chemistry, College of Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Raju Suresh Kumar
- Department of Chemistry, College of Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Qingsong Ye
- Center of Regenerative Medicine, Renmin Hospital of Wuhan University, Wuhan, China
- School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
- *Correspondence: Qingsong Ye, ; Akon Higuchi, ; Hao Chen, ; Tzu-Cheng Sung,
| | - Akon Higuchi
- School of Biomedical Engineering, The Eye Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China
- Department of Reproduction, National Center for Child Health and Development, Tokyo, Japan
- Department of Chemical and Materials Engineering, National Central University, Taoyuan, Taiwan
- Department of Chemical Engineering and R&D Center for Membrane Technology, Chung Yuan Christian University, Taoyuan, Taiwan
- *Correspondence: Qingsong Ye, ; Akon Higuchi, ; Hao Chen, ; Tzu-Cheng Sung,
| | - Hao Chen
- School of Biomedical Engineering, The Eye Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China
- *Correspondence: Qingsong Ye, ; Akon Higuchi, ; Hao Chen, ; Tzu-Cheng Sung,
| | - Tzu-Cheng Sung
- School of Biomedical Engineering, The Eye Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China
- *Correspondence: Qingsong Ye, ; Akon Higuchi, ; Hao Chen, ; Tzu-Cheng Sung,
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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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Kovacevic B, Jones M, Ionescu C, Walker D, Wagle S, Chester J, Foster T, Brown D, Mikov M, Mooranian A, Al-Salami H. The emerging role of bile acids as critical components in nanotechnology and bioengineering: Pharmacology, formulation optimizers and hydrogel-biomaterial applications. Biomaterials 2022; 283:121459. [PMID: 35303546 DOI: 10.1016/j.biomaterials.2022.121459] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 02/27/2022] [Accepted: 03/04/2022] [Indexed: 12/16/2022]
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Kim GJ, Lee KJ, Choi JW, An JH. Modified Industrial Three-Dimensional Polylactic Acid Scaffold Cell Chip Promotes the Proliferation and Differentiation of Human Neural Stem Cells. Int J Mol Sci 2022; 23:ijms23042204. [PMID: 35216320 PMCID: PMC8879874 DOI: 10.3390/ijms23042204] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 02/11/2022] [Accepted: 02/15/2022] [Indexed: 02/01/2023] Open
Abstract
In this study, we fabricated a three-dimensional (3D) scaffold using industrial polylactic acid (PLA), which promoted the proliferation and differentiation of human neural stem cells. An industrial PLA 3D scaffold (IPTS) cell chip with a square-shaped pattern was fabricated via computer-aided design and printed using a fused deposition modeling technique. To improve cell adhesion and cell differentiation, we coated the IPTS cell chip with gold nanoparticles (Au-NPs), nerve growth factor (NGF) protein, an NGF peptide fragment, and sonic hedgehog (SHH) protein. The proliferation of F3.Olig2 neural stem cells was increased in the IPTS cell chips coated with Au-NPs and NGF peptide fragments when compared with that of the cells cultured on non-coated IPTS cell chips. Cells cultured on the IPTS-SHH cell chip also showed high expression of motor neuron cell-specific markers, such as HB9 and TUJ-1. Therefore, we suggest that the newly engineered industrial PLA scaffold is an innovative tool for cell proliferation and motor neuron differentiation.
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Affiliation(s)
- Gyeong-Ji Kim
- Department of Biomedical Engineering, Sogang University, Seoul 04107, Korea;
- Department of Food and Nutrition, KC University, Seoul 07661, Korea
| | - Kwon-Jai Lee
- College of H-LAC, Daejeon University, Daejeon 34520, Korea;
| | - Jeong-Woo Choi
- Department of Biomedical Engineering, Sogang University, Seoul 04107, Korea;
- Department of Chemical and Biomolecular Engineering, Sogang University, Seoul 04107, Korea
- Correspondence: (J.-W.C.); (J.H.A.); Tel.: +82-2-705-8480 (J.-W.C.); +82-2-2600-2566 (J.H.A.)
| | - Jeung Hee An
- Department of Food and Nutrition, KC University, Seoul 07661, Korea
- Correspondence: (J.-W.C.); (J.H.A.); Tel.: +82-2-705-8480 (J.-W.C.); +82-2-2600-2566 (J.H.A.)
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Chen Y, Huang H, Li G, Yu J, Fang F, Qiu W. Dental-derived mesenchymal stem cell sheets: a prospective tissue engineering for regenerative medicine. Stem Cell Res Ther 2022; 13:38. [PMID: 35093155 PMCID: PMC8800229 DOI: 10.1186/s13287-022-02716-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 12/28/2021] [Indexed: 12/16/2022] Open
Abstract
Stem cells transplantation is the main method of tissue engineering regeneration treatment, the viability and therapeutic efficiency are limited. Scaffold materials also play an important role in tissue engineering, whereas there are still many limitations, such as rejection and toxic side effects caused by scaffold materials. Cell sheet engineering is a scaffold-free tissue technology, which avoids the side effects of traditional scaffolds and maximizes the function of stem cells. It is increasingly being used in the field of tissue regenerative medicine. Dental-derived mesenchymal stem cells (DMSCs) are multipotent cells that exist in various dental tissues and can be used in stem cell-based therapy, which is impactful in regenerative medicine. Emerging evidences show that cell sheets derived from DMSCs have better effects in the field of regenerative medicine applications. Extracellular matrix (ECM) is the main component of cell sheets, which is a dynamic repository of signalling biological molecules and has a variety of biological functions and may play an important role in the application of cell sheets. In this review, we summarized the application status, mechanisms that sheets and ECM may play and future prospect of DMSC sheets on regeneration medicine.
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Affiliation(s)
- Yuanting Chen
- Department of Stomatology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, People's Republic of China
| | - Huacong Huang
- School of Stomatology, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, People's Republic of China
| | - Gaoxing Li
- School of Stomatology, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, People's Republic of China
| | - Jianyu Yu
- School of Stomatology, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, People's Republic of China
| | - Fuchun Fang
- Department of Stomatology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, People's Republic of China.
| | - Wei Qiu
- Department of Stomatology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, People's Republic of China.
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Gao J, Zhang J, Xia L, Liang X, Ding W, Song M, Li L, Jia Z. Up-regulation of caveolin 1 mediated by chitosan activates Wnt/ β-catenin pathway in chronic refractory wound diabetic rat model. Bioengineered 2022; 13:1388-1398. [PMID: 35000526 PMCID: PMC8805831 DOI: 10.1080/21655979.2021.2017625] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Diabetes mellitus (DM) can be implicated in the perturbations of vascular integrity and the dysfunction of angiogenesis. Chitosan has the advantage of promoting the vascular endothelial cell proliferation. However, the molecular mechanism of action in the promotion of wound healing by chitosan derivatives is still debated. In the current study, DM with chronic wound (CW) model rats were prepared and treated with chitosan. Vascular endothelial cells isolated from granulation tissues were conducted by RNA sequencing. Two thousand three hundred and sixteen genes were up-regulated, while 1,864 genes were down-regulated after chitosan treatment compared to CW group. Here, we observed that caveolin 1 (CAV1) was highly expressed induced by chitosan. Furthermore, we observed that CAV1 knockdown could compromise the activation of Wnt pathway by reduction of β-catenin in rat aortic endothelial cells (RAOECs) and brain endothelium four cells (RBE4s). Moreover, we determined a direct interaction between CAV1 and β-catenin by IP assay. The C-terminus of CAV1 and β-catenin (24 to 586 amino acids) contributed to the interaction of these two proteins. Finally, the protein docking analysis indicated that the fragments of β-catenin (253–261 ‘FYAITTLHN’ and 292–303 ‘KFLAITTDCLQI’) might have affected the structure by CAV1 and facilitated the resistance to degradation. Taken together, our study demonstrates that chitosan can up-regulate CAV1 expression, and CAV1 can interact with β-catenin for promotion of canonical Wnt signaling pathway activity. Our results deepens the molecular mechanism of the Wnt pathway in vascular endothelial cells and is beneficial to developing new targets to assist in enhancing the pharmacological effect of chitosan on wound healing and angiogenesis against DM.
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Affiliation(s)
- Jie Gao
- Department of peripheral vascular diseases, First Affiliated hospital, Heilongjiang University of Traditional Chinese Medicine, Harbin City, Heilongjiang, China
| | - Jiayuan Zhang
- School of Stomatology, Qiqihar Medical University, Qiqihar, China
| | - Lianheng Xia
- Department of peripheral vascular diseases, First Affiliated hospital, Heilongjiang University of Traditional Chinese Medicine, Harbin City, Heilongjiang, China
| | - Xuewei Liang
- Department of peripheral vascular diseases, First Affiliated hospital, Heilongjiang University of Traditional Chinese Medicine, Harbin City, Heilongjiang, China
| | - Wukun Ding
- Department of peripheral vascular diseases, First Affiliated hospital, Heilongjiang University of Traditional Chinese Medicine, Harbin City, Heilongjiang, China
| | - Meiyu Song
- Department of peripheral vascular diseases, First Affiliated hospital, Heilongjiang University of Traditional Chinese Medicine, Harbin City, Heilongjiang, China
| | - Linggen Li
- Department of peripheral vascular diseases, First Affiliated hospital, Heilongjiang University of Traditional Chinese Medicine, Harbin City, Heilongjiang, China
| | - Zhen Jia
- Department of peripheral vascular diseases, First Affiliated hospital, Heilongjiang University of Traditional Chinese Medicine, Harbin City, Heilongjiang, China
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Pilbauerova N, Schmidt J, Soukup T, Duska J, Suchanek J. Intra-Individual Variability of Human Dental Pulp Stem Cell Features Isolated from the Same Donor. Int J Mol Sci 2021; 22:ijms222413515. [PMID: 34948330 PMCID: PMC8709021 DOI: 10.3390/ijms222413515] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 12/10/2021] [Accepted: 12/13/2021] [Indexed: 02/07/2023] Open
Abstract
It is primarily important to define the standard features and factors that affect dental pulp stem cells (DPSCs) for their broader use in tissue engineering. This study aimed to verify whether DPSCs isolated from various teeth extracted from the same donor exhibit intra-individual variability and what the consequences are for their differentiation potential. The heterogeneity determination was based on studying the proliferative capacity, viability, expression of phenotypic markers, and relative length of telomere chromosomes. The study included 14 teeth (6 molars and 8 premolars) from six different individuals ages 12 to 16. We did not observe any significant intra-individual variability in DPSC size, proliferation rate, viability, or relative telomere length change within lineages isolated from different teeth but the same donor. The minor non-significant variances in phenotype were probably mainly because DPSC cell lines comprised heterogeneous groups of undifferentiated cells independent of the donor. The other variances were seen in DPSC lineages isolated from the same donor, but the teeth were in different stages of root development. We also did not observe any changes in the ability of cells to differentiate into mature cell lines—chondrocytes, osteocytes, and adipocytes. This study is the first to analyze the heterogeneity of DPSC dependent on a donor.
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Affiliation(s)
- Nela Pilbauerova
- Department of Dentistry, Charles University, Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic; (N.P.); (J.D.); (J.S.)
| | - Jan Schmidt
- Department of Dentistry, Charles University, Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic; (N.P.); (J.D.); (J.S.)
- Correspondence: ; Tel.: +420-495-832-634
| | - Tomas Soukup
- Department of Histology and Embryology, Charles University, Faculty of Medicine in Hradec Kralove, Simkova 870, 500 03 Hradec Kralove, Czech Republic;
| | - Jan Duska
- Department of Dentistry, Charles University, Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic; (N.P.); (J.D.); (J.S.)
| | - Jakub Suchanek
- Department of Dentistry, Charles University, Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic; (N.P.); (J.D.); (J.S.)
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Advanced approaches to regenerate spinal cord injury: The development of cell and tissue engineering therapy and combinational treatments. Biomed Pharmacother 2021; 146:112529. [PMID: 34906773 DOI: 10.1016/j.biopha.2021.112529] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 12/07/2021] [Accepted: 12/08/2021] [Indexed: 12/13/2022] Open
Abstract
Spinal cord injury (SCI) is a central nervous system (CNS) devastate event that is commonly caused by traumatic or non-traumatic events. The reinnervation of spinal cord axons is hampered through a myriad of devices counting on the damaged myelin, inflammation, glial scar, and defective inhibitory molecules. Unfortunately, an effective treatment to completely repair SCI and improve functional recovery has not been found. In this regard, strategies such as using cells, biomaterials, biomolecules, and drugs have been reported to be effective for SCI recovery. Furthermore, recent advances in combinatorial treatments, which address various aspects of SCI pathophysiology, provide optimistic outcomes for spinal cord regeneration. According to the global importance of SCI, the goal of this article review is to provide an overview of the pathophysiology of SCI, with an emphasis on the latest modes of intervention and current advanced approaches for the treatment of SCI, in conjunction with an assessment of combinatorial approaches in preclinical and clinical trials. So, this article can give scientists and clinicians' clues to help them better understand how to construct preclinical and clinical studies that could lead to a breakthrough in spinal cord regeneration.
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Bar JK, Lis-Nawara A, Grelewski PG. Dental Pulp Stem Cell-Derived Secretome and Its Regenerative Potential. Int J Mol Sci 2021; 22:ijms222112018. [PMID: 34769446 PMCID: PMC8584775 DOI: 10.3390/ijms222112018] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 11/02/2021] [Accepted: 11/04/2021] [Indexed: 12/11/2022] Open
Abstract
The therapeutic potential of the dental pulp stem (DSC) cell-derived secretome, consisting of various biomolecules, is undergoing intense research. Despite promising in vitro and in vivo studies, most DSC secretome-based therapies have not been implemented in human medicine because the paracrine effect of the bioactive factors secreted by human dental pulp stem cells (hDPSCs) and human exfoliated deciduous teeth (SHEDs) is not completely understood. In this review, we outline the current data on the hDPSC- and SHED-derived secretome as a potential candidate in the regeneration of bone, cartilage, and nerve tissue. Published reports demonstrate that the dental MSC-derived secretome/conditional medium may be effective in treating neurodegenerative diseases, neural injuries, cartilage defects, and repairing bone by regulating neuroprotective, anti-inflammatory, antiapoptotic, and angiogenic processes through secretome paracrine mechanisms. Dental MSC-secretomes, similarly to the bone marrow MSC-secretome activate molecular and cellular mechanisms, which determine the effectiveness of cell-free therapy. Many reports emphasize that dental MSC-derived secretomes have potential application in tissue-regenerating therapy due to their multidirectional paracrine effect observed in the therapy of many different injured tissues.
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Lai BQ, Zeng X, Han WT, Che MT, Ding Y, Li G, Zeng YS. Stem cell-derived neuronal relay strategies and functional electrical stimulation for treatment of spinal cord injury. Biomaterials 2021; 279:121211. [PMID: 34710795 DOI: 10.1016/j.biomaterials.2021.121211] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 10/09/2021] [Accepted: 10/20/2021] [Indexed: 01/06/2023]
Abstract
The inability of adult mammals to recover function lost after severe spinal cord injury (SCI) has been known for millennia and is mainly attributed to a failure of brain-derived nerve fiber regeneration across the lesion. Potential approaches to re-establishing locomotor function rely on neuronal relays to reconnect the segregated neural networks of the spinal cord. Intense research over the past 30 years has focused on endogenous and exogenous neuronal relays, but progress has been slow and the results often controversial. Treatments with stem cell-derived neuronal relays alone or together with functional electrical stimulation offer the possibility of improved repair of neuronal networks. In this review, we focus on approaches to recovery of motor function in paralyzed patients after severe SCI based on novel therapies such as implantation of stem cell-derived neuronal relays and functional electrical stimulation. Recent research progress offers hope that SCI patients will one day be able to recover motor function and sensory perception.
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Affiliation(s)
- Bi-Qin Lai
- Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China
| | - Xiang Zeng
- Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China
| | - Wei-Tao Han
- Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China
| | - Ming-Tian Che
- Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China
| | - Ying Ding
- Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China
| | - Ge Li
- Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China
| | - Yuan-Shan Zeng
- Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China; Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China; Institute of Spinal Cord Injury, Sun Yat-sen University, Guangzhou, 510120, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan, School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
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Jiang R, Wang M, Shen X, Huang S, Han J, Li L, Xu Z, Jiang C, Zhou Q, Feng X. SUMO1 modification of IGF-1R combining with SNAI2 inhibited osteogenic differentiation of PDLSCs stimulated by high glucose. Stem Cell Res Ther 2021; 12:543. [PMID: 34663464 PMCID: PMC8522165 DOI: 10.1186/s13287-021-02618-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 06/15/2021] [Indexed: 01/09/2023] Open
Abstract
Background Periodontal disease, an oral disease characterized by loss of alveolar bone and progressive teeth loss, is the sixth major complication of diabetes. It is spreading worldwide as it is difficult to be cured. The insulin-like growth factor 1 receptor (IGF-1R) plays an important role in regulating functional impairment associated with diabetes. However, it is unclear whether IGF-1R expression in periodontal tissue is related to alveolar bone destruction in diabetic patients. SUMO modification has been reported in various diseases and is associated with an increasing number of biological processes, but previous studies have not focused on diabetic periodontitis. This study aimed to explore the role of IGF-1R in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in high glucose and control the multiple downstream damage signal factors. Methods PDLSCs were isolated and cultured after extraction of impacted teeth from healthy donors or subtractive orthodontic extraction in adolescents. PDLSCs were cultured in the osteogenic medium with different glucose concentrations prepared by medical 5% sterile glucose solution. The effects of different glucose concentrations on the osteogenic differentiation ability of PDLSCs were studied at the genetic and cellular levels by staining assay, Western Blot, RT-PCR, Co-IP and cytofluorescence. Results We found that SNAI2, RUNX2 expression decreased in PDLSCs cultured in high glucose osteogenic medium compared with that in normal glucose osteogenic medium, which were osteogenesis-related marker. In addition, the IGF-1R expression, sumoylation of IGF-1R and osteogenic differentiation in PDLSCs cultured in high glucose osteogenic medium were not consistent with those cultured in normal glucose osteogenic medium. However, osteogenic differentiation of PDLCSs enhanced after adding IGF-1R inhibitors to high glucose osteogenic medium. Conclusion Our data demonstrated that SUMO1 modification of IGF-1R inhibited osteogenic differentiation of PDLSCs by binding to SNAI2 in high glucose environment, a key factor leading to alveolar bone loss in diabetic patients. Thus we could maximize the control of multiple downstream damage signaling factors and bring new hope for alveolar bone regeneration in diabetic patients.
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Affiliation(s)
- Rongrong Jiang
- Department of Stomatology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, China
| | - Miao Wang
- Department of Stomatology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, China
| | - Xiaobo Shen
- Department of Stomatology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, China
| | - Shuai Huang
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, Nantong, 226001, Jiangsu, China
| | - Jianpeng Han
- Department of Stomatology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, China
| | - Lei Li
- Department of Stomatology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, China
| | - Zhiliang Xu
- Department of Stomatology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, China
| | - Chengfeng Jiang
- Department of Stomatology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, China
| | - Qiao Zhou
- Department of Stomatology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, China.
| | - Xingmei Feng
- Department of Stomatology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, China.
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Mukherjee S, Yadav G, Kumar R. Recent trends in stem cell-based therapies and applications of artificial intelligence in regenerative medicine. World J Stem Cells 2021; 13:521-541. [PMID: 34249226 PMCID: PMC8246250 DOI: 10.4252/wjsc.v13.i6.521] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/22/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
Stem cells are undifferentiated cells that can self-renew and differentiate into diverse types of mature and functional cells while maintaining their original identity. This profound potential of stem cells has been thoroughly investigated for its significance in regenerative medicine and has laid the foundation for cell-based therapies. Regenerative medicine is rapidly progressing in healthcare with the prospect of repair and restoration of specific organs or tissue injuries or chronic disease conditions where the body’s regenerative process is not sufficient to heal. In this review, the recent advances in stem cell-based therapies in regenerative medicine are discussed, emphasizing mesenchymal stem cell-based therapies as these cells have been extensively studied for clinical use. Recent applications of artificial intelligence algorithms in stem cell-based therapies, their limitation, and future prospects are highlighted.
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Affiliation(s)
- Sayali Mukherjee
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow 226028, Uttar Pradesh, India
| | - Garima Yadav
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow 226028, Uttar Pradesh, India
| | - Rajnish Kumar
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow 226028, Uttar Pradesh, India
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43
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Trends of Chitosan Based Delivery Systems in Neuroregeneration and Functional Recovery in Spinal Cord Injuries. POLYSACCHARIDES 2021. [DOI: 10.3390/polysaccharides2020031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Spinal cord injury (SCI) is one of the most complicated nervous system injuries with challenging treatment and recovery. Regenerative biomaterials such as chitosan are being reported for their wide use in filling the cavities, deliver curative drugs, and also provide adsorption sites for transplanted stem cells. Biomaterial scaffolds utilizing chitosan have shown certain therapeutic effects on spinal cord injury repair with some limitations. Chitosan-based delivery in stem cell transplantation is another strategy that has shown decent success. Stem cells can be directed to differentiate into neurons or glia in vitro. Stem cell-based therapy, biopolymer chitosan delivery strategies, and scaffold-based therapeutic strategies have been advancing as a combinatorial approach for spinal cord injury repair. In this review, we summarize the recent progress in the treatment strategies of SCI due to the use of bioactivity of chitosan-based drug delivery systems. An emphasis on the role of chitosan in neural regeneration has also been highlighted.
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Takeshita S, Zhao S, Malfait WJ, Koebel MM. Chemie der Chitosan‐Aerogele: Lenkung der dreidimensionalen Poren für maßgeschneiderte Anwendungen. Angew Chem Int Ed Engl 2021. [DOI: 10.1002/ange.202003053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Satoru Takeshita
- Building Energy Materials & Components Laboratory Eidgenössische Materialprüfungs- und Forschungsanstalt (Empa) Überlandstrasse 129 CH-8600 Dübendorf Schweiz
- Research Institute for Chemical Process Technology National Institute of Advanced Industrial Science and Technology (AIST) Tsukuba Central 5, 1-1-1 Higashi 3058565 Tsukuba Japan
| | - Shanyu Zhao
- Building Energy Materials & Components Laboratory Eidgenössische Materialprüfungs- und Forschungsanstalt (Empa) Überlandstrasse 129 CH-8600 Dübendorf Schweiz
| | - Wim J. Malfait
- Building Energy Materials & Components Laboratory Eidgenössische Materialprüfungs- und Forschungsanstalt (Empa) Überlandstrasse 129 CH-8600 Dübendorf Schweiz
| | - Matthias M. Koebel
- Building Energy Materials & Components Laboratory Eidgenössische Materialprüfungs- und Forschungsanstalt (Empa) Überlandstrasse 129 CH-8600 Dübendorf Schweiz
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45
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Advances and Perspectives in Dental Pulp Stem Cell Based Neuroregeneration Therapies. Int J Mol Sci 2021; 22:ijms22073546. [PMID: 33805573 PMCID: PMC8036729 DOI: 10.3390/ijms22073546] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/25/2021] [Accepted: 03/26/2021] [Indexed: 02/06/2023] Open
Abstract
Human dental pulp stem cells (hDPSCs) are some of the most promising stem cell types for regenerative therapies given their ability to grow in the absence of serum and their realistic possibility to be used in autologous grafts. In this review, we describe the particular advantages of hDPSCs for neuroregenerative cell therapies. We thoroughly discuss the knowledge about their embryonic origin and characteristics of their postnatal niche, as well as the current status of cell culture protocols to maximize their multilineage differentiation potential, highlighting some common issues when assessing neuronal differentiation fates of hDPSCs. We also review the recent progress on neuroprotective and immunomodulatory capacity of hDPSCs and their secreted extracellular vesicles, as well as their combination with scaffold materials to improve their functional integration on the injured central nervous system (CNS) and peripheral nervous system (PNS). Finally, we offer some perspectives on the current and possible future applications of hDPSCs in neuroregenerative cell therapies.
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Thermosensitive quaternized chitosan hydrogel scaffolds promote neural differentiation in bone marrow mesenchymal stem cells and functional recovery in a rat spinal cord injury model. Cell Tissue Res 2021; 385:65-85. [PMID: 33760948 DOI: 10.1007/s00441-021-03430-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 01/26/2021] [Indexed: 12/24/2022]
Abstract
A thermosensitive quaternary ammonium chloride chitosan/β-glycerophosphate (HACC/β-GP) hydrogel scaffold combined with bone marrow mesenchymal stem cells (BMSCs) transfected with an adenovirus containing the glial cell-derived neurotrophic factor (GDNF) gene (Ad-rGDNF) was applied to spinal cord injury (SCI) repair. The BMSCs from rats were transfected with Ad-rGDNF, resulting in the expression of GDNF mRNA in the BMSCs increasing and their spontaneous differentiation into neural-like cells expressing neural markers such as NF-200 and GFAP. After incubation with HACC/β-GP hydrogel scaffolds for 2 weeks, neuronal differentiation of the BMSCs was confirmed using immunofluorescence (IF), and the expression of GDNF by the BMSCs was detected by Western blot at different time points. MTT assay and scanning electron microscopy confirmed that the HACC scaffold provides a non-cytotoxic microenvironment that supports cell adhesion and growth. Rats with SCI were treated with BMSCs, BMSCs carried by the HACC/β-GP hydrogel (HACC/BMSCs), Ad-rGDNF-BMSCs, or Ad-rGDNF-BMSCs carried by the hydrogel (HACC/GDNF-BMSCs). Animals were sacrificed at 2, 4, and 6 weeks of treatment. IF staining and Western blot were performed to detect the expression of NeuN, NF-200, GFAP, CS56, and Bax in the lesion sites of the injured spinal cord. Upon treatment with HACC/BMSCs, NF200 and GFAP were upregulated but CS56 and Bax were downregulated in the SCI lesion site. Furthermore, transplantation of HACC/GDNF-BMSCs into an SCI rat model significantly improved BBB scores and regeneration of the spinal cord. Thus, HACC/β-GP hydrogel scaffolds show promise for functional recovery in spinal cord injury patients.
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Amini S, Salehi H, Setayeshmehr M, Ghorbani M. Natural and synthetic polymeric scaffolds used in peripheral nerve tissue engineering: Advantages and disadvantages. POLYM ADVAN TECHNOL 2021. [DOI: 10.1002/pat.5263] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- Shahram Amini
- Department of Anatomical Sciences and Molecular Biology, School of Medicine Isfahan University of Medical Sciences hezarjerib Isfahan Iran
- Student Research Committee Baqiyatallah University of Medical Sciences Tehran Iran
| | - Hossein Salehi
- Department of Anatomical Sciences and Molecular Biology, School of Medicine Isfahan University of Medical Sciences hezarjerib Isfahan Iran
| | - Mohsen Setayeshmehr
- Department of Biomaterials, Tissue Engineering and Nanotechnology, School of Advanced Technologies in Medicine Isfahan University of Medical Sciences Isfahan Iran
| | - Masoud Ghorbani
- Applied Biotechnology Research Center Baqiyatallah University of Medical Sciences Tehran Iran
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48
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Electrospraying: A facile technology unfolding the chitosan based drug delivery and biomedical applications. Eur Polym J 2021. [DOI: 10.1016/j.eurpolymj.2021.110326] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Physical and Biological Properties of a Chitosan Hydrogel Scaffold Associated to Photobiomodulation Therapy for Dental Pulp Regeneration: An In Vitro and In Vivo Study. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6684667. [PMID: 33575339 PMCID: PMC7857869 DOI: 10.1155/2021/6684667] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 01/07/2021] [Accepted: 01/12/2021] [Indexed: 01/06/2023]
Abstract
Background The regeneration of dental pulp, especially in cases of pulp death of immature teeth, is the goal of the regenerative endodontic procedures (REPs) that are based on tissue engineering principles, consisting of stem cells, growth factors, and scaffolds. Photobiomodulation therapy (PBMT) showed to improve dental pulp regeneration through cell homing approaches in preclinical studies and has been proposed as the fourth element of tissue engineering. However, when a blood clot was used as a scaffold in one of these previous studies, only 30% of success was achieved. The authors pointed out the instability of the blood clot as the regeneration shortcoming. Then, to circumvent this problem, a new scaffold was developed to be applied with the blood clot. The hypothesis of the present study was that an experimental injectable chitosan hydrogel would facilitate the three-dimensional spatial organization of endogenous stem cells in dental pulp regeneration with no interference on the positive influence of PBMT. Methods For the in vitro analysis, stem cells from the apical papilla (SCAPs) were characterized by flow cytometry and applied in the chitosan scaffold for evaluating adhesion, migration, and proliferation. For the in vivo analysis, the chitosan scaffold was applied in a rodent orthotopic dental pulp regeneration model under the influence of PBMT (660 nm; power output of 20 mW, beam area of 0.028 cm2, and energy density of 5 J/cm2). Results The scaffold tested in this study allowed significantly higher viability, proliferation, and migration of SCAPs in vitro when PBMT was applied, especially with the energy density of 5 J/cm2. These results were in consonance to those of the in vivo data, where pulp-like tissue formation was observed inside the root canal. Conclusion Chitosan hydrogel when applied with a blood clot and PBMT could in the future improve previous results of dental pulp regeneration through cell homing approaches.
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Stem Cell-based Dental Pulp Regeneration: Insights From Signaling Pathways. Stem Cell Rev Rep 2021; 17:1251-1263. [PMID: 33459973 DOI: 10.1007/s12015-020-10117-3] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/29/2020] [Indexed: 02/05/2023]
Abstract
Deep caries, trauma, and severe periodontitis result in pulpitis, pulp necrosis, and eventually pulp loss. However, no clinical therapy can regenerate lost pulp. A novel pulp regeneration strategy for clinical application is urgently needed. Signaling transduction plays an essential role in regulating the regenerative potentials of dental stem cells. Cytokines or growth factors, such as stromal cell-derived factor (SDF), fibroblast growth factor (FGF), bone morphogenetic protein (BMP), vascular endothelial growth factor (VEGF), WNT, can promote the migration, proliferation, odontogenic differentiation, pro-angiogenesis, and pro-neurogenesis potentials of dental stem cells respectively. Using the methods of signaling modulation including growth factors delivery, genetic modification, and physical stimulation has been applied in multiple preclinical studies of pulp regeneration based on cell transplantation or cell homing. Transplanting dental stem cells and growth factors encapsulated into scaffold regenerated vascularized pulp-like tissue in the root canal. Also, injecting a flowable scaffold only with chemokines recruited endogenous stem/progenitor cells for pulp regeneration. Notably, dental pulp regeneration has gradually developed into the clinical phase. These findings enlightened us on a novel strategy for structural and functional pulp regeneration through elaborate modulation of signaling transduction spatially and temporally via clinically applicable growth factors delivery. But challenges, such as the adverse effects of unphysiological signaling activation, the controlled drug release system, and the safety of gene modulation, are necessary to be tested in future works for promoting the clinical translation of pulp regeneration.
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