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Kamarehei F, Saleh GN. Tissue regeneration therapy by Nano composite scaffolds based on PLGA hydrogel embedded with human dental pulp stem cells: a systematic review. Am J Transl Res 2024; 16:1521-1530. [PMID: 38883345 PMCID: PMC11170567 DOI: 10.62347/qbko6417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 02/28/2024] [Indexed: 06/18/2024]
Abstract
Tissue regeneration is the procedure of renewal, restoration and growth of injured tissues and defective organs including nerve, bone, tooth, cartilage and blood vessels. Repair process of damaged tissues needs non-invasive methods; so, the scientists have recently focused on alternative treatment pathways. Nano gels based on Poly Lactic-co-Glycolic Acid have been designed for different purposes in medicine. It is a biodegradable and biocompatible polymer composite. Also, human dental pulp stem cells embedded in the Poly Lactic-co-Glycolic Acid scaffold have proliferation ability and differentiation potential. They can differentiate into different cell lineages, including bone, cartilage, nerve, tooth and other tissues. So, this treatment technology can be used for tissue engineering in regenerative medicine. On the other hand, this structure is a promising application for targeted cancer therapy. Therefore, this review studied tissue, especially tooth regeneration based on the new designed Nano composite scaffolds embedded with Poly Lactic-co-Glycolic Acid hydrogel and dental pulp stem cells.
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Affiliation(s)
- Farideh Kamarehei
- Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences Hamadan, Iran
| | - Goran Noori Saleh
- Department of Nursing, Tishk International University-Kurdistan Region Iraq
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2
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Santilli F, Fabrizi J, Santacroce C, Caissutti D, Spinello Z, Candelise N, Lancia L, Pulcini F, Delle Monache S, Mattei V. Analogies and Differences Between Dental Stem Cells: Focus on Secretome in Combination with Scaffolds in Neurological Disorders. Stem Cell Rev Rep 2024; 20:159-174. [PMID: 37962698 PMCID: PMC10799818 DOI: 10.1007/s12015-023-10652-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/02/2023] [Indexed: 11/15/2023]
Abstract
Mesenchymal stem cells (MSCs) are well known for their beneficial effects, differentiation capacity and regenerative potential. Dental-derived MSCs (DSCs) are more easily accessible and have a non-invasive isolation method rather than MSCs isolated from other sources (umbilical cord, bone marrow, and adipose tissue). In addition, DSCs appear to have a relevant neuro-regenerative potential due to their neural crest origin. However, it is now known that the beneficial effects of MSCs depend, at least in part, on their secretome, referring to all the bioactive molecules (neurotrophic factors) released in the conditioned medium (CM) or in the extracellular vesicles (EVs) in particular exosomes (Exos). In this review, we described the similarities and differences between various DSCs. Our focus was on the secretome of DSCs and their applications in cell therapy for neurological disorders. For neuro-regenerative purposes, the secretome of different DSCs has been tested. Among these, the secretome of dental pulp stem cells and stem cells from human exfoliated deciduous teeth have been the most widely studied. Both CM and Exos obtained from DSCs have been shown to promote neurite outgrowth and neuroprotective effects as well as their combination with scaffold materials (to improve their functional integration in the tissue). For these reasons, the secretome obtained from DSCs in combination with scaffold materials may represent a promising tissue engineering approach for neuroprotective and neuro-regenerative treatments.
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Affiliation(s)
- Francesca Santilli
- Biomedicine and Advanced Technologies Rieti Center, "Sabina Universitas", Via A.M. Ricci 35/A, 02100, Rieti, Italy
| | - Jessica Fabrizi
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Costantino Santacroce
- Biomedicine and Advanced Technologies Rieti Center, "Sabina Universitas", Via A.M. Ricci 35/A, 02100, Rieti, Italy
| | - Daniela Caissutti
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Zaira Spinello
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Niccolò Candelise
- National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 29900161, Rome, Italy
| | - Loreto Lancia
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy
| | - Fanny Pulcini
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy
| | - Simona Delle Monache
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy.
| | - Vincenzo Mattei
- Dipartimento di Scienze della Vita, della Salute e delle Professioni Sanitarie, Link Campus University, Via del Casale di San Pio V 44, 00165, Rome, Italy.
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Meng Q, Burrell JC, Zhang Q, Le AD. Potential Application of Orofacial MSCs in Tissue Engineering Nerve Guidance for Peripheral Nerve Injury Repair. Stem Cell Rev Rep 2023; 19:2612-2631. [PMID: 37642899 DOI: 10.1007/s12015-023-10609-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/15/2023] [Indexed: 08/31/2023]
Abstract
Injury to the peripheral nerve causes potential loss of sensory and motor functions, and peripheral nerve repair (PNR) remains a challenging endeavor. The current clinical methods of nerve repair, such as direct suture, autografts, and acellular nerve grafts (ANGs), exhibit their respective disadvantages like nerve tension, donor site morbidity, size mismatch, and immunogenicity. Even though commercially available nerve guidance conduits (NGCs) have demonstrated some clinical successes, the overall clinical outcome is still suboptimal, especially for nerve injuries with a large gap (≥ 3 cm) due to the lack of biologics. In the last two decades, the combination of advanced tissue engineering technologies, stem cell biology, and biomaterial science has significantly advanced the generation of a new generation of NGCs incorporated with biological factors or supportive cells, including mesenchymal stem cells (MSCs), which hold great promise to enhance peripheral nerve repair/regeneration (PNR). Orofacial MSCs are emerging as a unique source of MSCs for PNR due to their neural crest-origin and easy accessibility. In this narrative review, we have provided an update on the pathophysiology of peripheral nerve injury and the properties and biological functions of orofacial MSCs. Then we have highlighted the application of orofacial MSCs in tissue engineering nerve guidance for PNR in various preclinical models and the potential challenges and future directions in this field.
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Affiliation(s)
- Qingyu Meng
- Department of Oral & Maxillofacial Surgery & Pharmacology, University of Pennsylvania School of Dental Medicine, 240 South 40Th Street, Philadelphia, PA, 19104, USA
| | - Justin C Burrell
- Department of Oral & Maxillofacial Surgery & Pharmacology, University of Pennsylvania School of Dental Medicine, 240 South 40Th Street, Philadelphia, PA, 19104, USA
| | - Qunzhou Zhang
- Department of Oral & Maxillofacial Surgery & Pharmacology, University of Pennsylvania School of Dental Medicine, 240 South 40Th Street, Philadelphia, PA, 19104, USA.
| | - Anh D Le
- Department of Oral & Maxillofacial Surgery & Pharmacology, University of Pennsylvania School of Dental Medicine, 240 South 40Th Street, Philadelphia, PA, 19104, USA.
- Department of Oral & Maxillofacial Surgery, Penn Medicine Hospital of the University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA, 19104, USA.
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4
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Yang C, Du XY, Luo W. Clinical application prospects and transformation value of dental follicle stem cells in oral and neurological diseases. World J Stem Cells 2023; 15:136-149. [PMID: 37181000 PMCID: PMC10173814 DOI: 10.4252/wjsc.v15.i4.136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/18/2023] [Accepted: 03/21/2023] [Indexed: 04/26/2023] Open
Abstract
Since dental pulp stem cells (DPSCs) were first reported, six types of dental SCs (DSCs) have been isolated and identified. DSCs originating from the craniofacial neural crest exhibit dental-like tissue differentiation potential and neuro-ectodermal features. As a member of DSCs, dental follicle SCs (DFSCs) are the only cell type obtained at the early developing stage of the tooth prior to eruption. Dental follicle tissue has the distinct advantage of large tissue volume compared with other dental tissues, which is a prerequisite for obtaining a sufficient number of cells to meet the needs of clinical applications. Furthermore, DFSCs exhibit a significantly higher cell proliferation rate, higher colony-formation capacity, and more primitive and better anti-inflammatory effects than other DSCs. In this respect, DFSCs have the potential to be of great clinical significance and translational value in oral and neurological diseases, with natural advantages based on their origin. Lastly, cryopreservation preserves the biological properties of DFSCs and enables them to be used as off-shelf products for clinical applications. This review summarizes and comments on the properties, application potential, and clinical transformation value of DFSCs, thereby inspiring novel perspectives in the future treatment of oral and neurological diseases.
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Affiliation(s)
- Chao Yang
- Research and Development Department, Shenzhen Uni-medica Technology Co., Ltd, Shenzhen 518051, Guangdong Province, China
- Department of Stomatology, The People’s Hospital of Longhua, Shenzhen 518109, Guangdong Province, China
| | - Xin-Ya Du
- Department of Stomatology, The People’s Hospital of Longhua, Shenzhen 518109, Guangdong Province, China
| | - Wen Luo
- Department of Stomatology, The First Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, China
- School of Stomatology, Hainan Medical University, Haikou 571199, Hainan Province, China
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Yang R, Pan J, Wang Y, Xia P, Tai M, Jiang Z, Chen G. Application and prospects of somatic cell reprogramming technology for spinal cord injury treatment. Front Cell Neurosci 2022; 16:1005399. [PMID: 36467604 PMCID: PMC9712200 DOI: 10.3389/fncel.2022.1005399] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 11/02/2022] [Indexed: 08/10/2023] Open
Abstract
Spinal cord injury (SCI) is a serious neurological trauma that is challenging to treat. After SCI, many neurons in the injured area die due to necrosis or apoptosis, and astrocytes, oligodendrocytes, microglia and other non-neuronal cells become dysfunctional, hindering the repair of the injured spinal cord. Corrective surgery and biological, physical and pharmacological therapies are commonly used treatment modalities for SCI; however, no current therapeutic strategies can achieve complete recovery. Somatic cell reprogramming is a promising technology that has gradually become a feasible therapeutic approach for repairing the injured spinal cord. This revolutionary technology can reprogram fibroblasts, astrocytes, NG2 cells and neural progenitor cells into neurons or oligodendrocytes for spinal cord repair. In this review, we provide an overview of the transcription factors, genes, microRNAs (miRNAs), small molecules and combinations of these factors that can mediate somatic cell reprogramming to repair the injured spinal cord. Although many challenges and questions related to this technique remain, we believe that the beneficial effect of somatic cell reprogramming provides new ideas for achieving functional recovery after SCI and a direction for the development of treatments for SCI.
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Affiliation(s)
- Riyun Yang
- Department of Histology and Embryology, Medical School of Nantong University, Nantong, China
| | - Jingying Pan
- Department of Histology and Embryology, Medical School of Nantong University, Nantong, China
| | - Yankai Wang
- Center for Basic Medical Research, Medical School of Nantong University, Nantong, China
| | - Panhui Xia
- Center for Basic Medical Research, Medical School of Nantong University, Nantong, China
| | - Mingliang Tai
- Center for Basic Medical Research, Medical School of Nantong University, Nantong, China
| | - Zhihao Jiang
- Center for Basic Medical Research, Medical School of Nantong University, Nantong, China
| | - Gang Chen
- Center for Basic Medical Research, Medical School of Nantong University, Nantong, China
- Key Laboratory of Neuroregeneration of Jiangsu and the Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
- Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, China
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Bi F, Xiong J, Han X, Yang C, Li X, Chen G, Guo W, Tian W. Dental follicle cells show potential for treating Parkinson's disease through dopaminergic-neuronogenic differentiation. Hum Cell 2022; 35:1708-1721. [PMID: 36040643 DOI: 10.1007/s13577-022-00774-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 08/20/2022] [Indexed: 11/04/2022]
Abstract
Among all the adult stem cells, odontogenic stem cells inherit the characterization of neurogenic potential of their precursor ones-the cranial crest cells. Dental follicle cells (DFCs), one of the special kind of odontogenic stem cells, are raising interest in applying to regenerative medicine for they possess multi-differentiation potential, relatively free access and ethic-friendly characteristic. Parkinson's disease (PD), as one of the common neurodegenerative disorders, affects about 0.3% of the general population. Stem cell therapies are thought to be effective to treat it. Aiming at tackling ethical-concernings, confined sources and practically applicational limits, we made use of dopaminergic neurongenic differentiation potential of the DFCs and dedicated every effort to applying them as promising cell source for treating PD. Dental follicle cells were cultured from human dental follicle tissues collected from 12 to 18-year-old teenagers' completely impacted third molars. Our data demonstrated that hDFCs were expressing mesenchymal stem cell-associated surface markers, and possessed the ability of osteogenic, adipogenic and neurogenic differentiation in vitro. Additionally, hDFCs formed neuron-like cells in vitro and in vivo, as well as expressing dopaminergic-neuronogenic marker-TH. Moreover, hDFCs survived in the transplanted areas of the Parkinson's disease model of mouse over six weeks post-surgery, and the number of TH-positive DFCs in the DFCs-Grafted group surpassed its counterpart of the MPTP group with statistically significant difference. This study indicated that hDFCs might be a promising source of dopaminergic neurons for functional transplantation, and encouraged further detailed studies on the potential of hDFCs for treating PD.
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Affiliation(s)
- Fei Bi
- Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, South Peoples Road, Chengdu, 610041, China
- National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, South Peoples Road, Chengdu, 610041, China
| | - Jie Xiong
- Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, South Peoples Road, Chengdu, 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xue Han
- Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, South Peoples Road, Chengdu, 610041, China
- National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, South Peoples Road, Chengdu, 610041, China
| | - Chao Yang
- Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, South Peoples Road, Chengdu, 610041, China
- National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xinghan Li
- Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, South Peoples Road, Chengdu, 610041, China
- National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Guoqing Chen
- Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, South Peoples Road, Chengdu, 610041, China
- National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Weihua Guo
- Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, South Peoples Road, Chengdu, 610041, China.
- National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
- Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, South Peoples Road, Chengdu, 610041, China.
| | - Weidong Tian
- Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, South Peoples Road, Chengdu, 610041, China.
- National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
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Natarajan ABMT, Sivadas VPD, Nair PDPD. 3D-printed biphasic scaffolds for the simultaneous regeneration of osteochondral tissues. Biomed Mater 2021; 16. [PMID: 34265754 DOI: 10.1088/1748-605x/ac14cb] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Accepted: 07/15/2021] [Indexed: 12/19/2022]
Abstract
Osteochondral tissue engineering (OCTE) involves the simulation of highly complex tissues with disparate biomechanical properties. OCTE is regarded as the best option for treating osteochondral defects, most of the drawbacks of current treatment methodologies can be addressed by this method. In recent years, the conventional scaffolds used in cartilage and bone regeneration are gradually being replaced by 3D printed scaffolds (3DP). In the present study, we devised the strategy of 3D printing for fabricating biphasic and integrated scaffolds that are loaded with bioactive factors for enhancing the osteochondral tissue regeneration. Polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA), is used along with bioactive factors (chondroitin sulphate and beta-tricalcium phosphate (βTCP)) for the upper cartilage and lower bone layer respectively. The 3D printed bi-layered scaffolds with varying infill density, to mimic the native tissue, are not previously explored for OCTE. Hence, we tested the simultaneous osteochondrogenic differentiation inducing potential of the aforesaid 3D printed biphasic scaffoldsin vitro, using rabbit adipose derived mesenchymal stem cells (ADMSCs). Further, the biphasic scaffolds were highly cytocompatible, with excellent cell adhesion properties and cellular morphology. Most importantly, these biphasic scaffolds directed the simultaneous differentiation of a single stem cell population in to two cell lineages (simultaneous differentiation of rabbit ADMSCs into chondrocytes and osteoblasts). Further, these scaffolds enhanced the production of ECM and induced robust expression of marker genes that is specific for respective cartilage and bone layers. The 3D printed OCTE scaffold of our study hence can simulate the native osteochondral unit and could be potential futuristic biomimetic scaffold for osteochondral defects. Furtherin vivostudies are warranted.
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Affiliation(s)
- Amrita Bds MTech Natarajan
- Division of Tissue Engineering and Regeneration Technologies, Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012, India
| | - Vp Ph D Sivadas
- Division of Tissue Engineering and Regeneration Technologies, Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012, India
| | - Prabha D Ph D Nair
- Division of Tissue Engineering and Regeneration Technologies, Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012, India
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Function of Dental Follicle Progenitor/Stem Cells and Their Potential in Regenerative Medicine: From Mechanisms to Applications. Biomolecules 2021; 11:biom11070997. [PMID: 34356621 PMCID: PMC8301812 DOI: 10.3390/biom11070997] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/04/2021] [Accepted: 07/04/2021] [Indexed: 02/06/2023] Open
Abstract
Dental follicle progenitor/stem cells (DFPCs) are a group of dental mesenchyme stem cells that lie in the dental follicle and play a critical role in tooth development and maintaining function. Originating from neural crest, DFPCs harbor a multipotential differentiation capacity. More importantly, they have superiorities, including the easy accessibility and abundant sources, active self-renewal ability and noncontroversial sources compared with other stem cells, making them an attractive candidate in the field of tissue engineering. Recent advances highlight the excellent properties of DFPCs in regeneration of orofacial tissues, including alveolar bone repair, periodontium regeneration and bio-root complex formation. Furthermore, they play a unique role in maintaining a favorable microenvironment for stem cells, immunomodulation and nervous related tissue regeneration. This review is intended to summarize the current knowledge of DFPCs, including their stem cell properties, physiological functions and clinical application potential. A deep understanding of DFPCs can thus inspire novel perspectives in regenerative medicine in the future.
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Key Markers and Epigenetic Modifications of Dental-Derived Mesenchymal Stromal Cells. Stem Cells Int 2021; 2021:5521715. [PMID: 34046069 PMCID: PMC8128613 DOI: 10.1155/2021/5521715] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/08/2021] [Accepted: 04/17/2021] [Indexed: 12/13/2022] Open
Abstract
As a novel research hotspot in tissue regeneration, dental-derived mesenchymal stromal cells (MSCs) are famous for their accessibility, multipotent differentiation ability, and high proliferation. However, cellular heterogeneity is a major obstacle to the clinical application of dental-derived MSCs. Here, we reviewed the heterogeneity of dental-derived MSCs firstly and then discussed the key markers and epigenetic modifications related to the proliferation, differentiation, immunomodulation, and aging of dental-derived MSCs. These messages help to control the composition and function of dental-derived MSCs and thus accelerate the translation of cell therapy into clinical practice.
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10
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Granz CL, Gorji A. Dental stem cells: The role of biomaterials and scaffolds in developing novel therapeutic strategies. World J Stem Cells 2020; 12:897-921. [PMID: 33033554 PMCID: PMC7524692 DOI: 10.4252/wjsc.v12.i9.897] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 06/05/2020] [Accepted: 08/16/2020] [Indexed: 02/06/2023] Open
Abstract
Dental stem cells (DSCs) are self-renewable cells that can be obtained easily from dental tissues, and are a desirable source of autologous stem cells. The use of DSCs for stem cell transplantation therapeutic approaches is attractive due to their simple isolation, high plasticity, immunomodulatory properties, and multipotential abilities. Using appropriate scaffolds loaded with favorable biomolecules, such as growth factors, and cytokines, can improve the proliferation, differentiation, migration, and functional capacity of DSCs and can optimize the cellular morphology to build tissue constructs for specific purposes. An enormous variety of scaffolds have been used for tissue engineering with DSCs. Of these, the scaffolds that particularly mimic tissue-specific micromilieu and loaded with biomolecules favorably regulate angiogenesis, cell-matrix interactions, degradation of extracellular matrix, organized matrix formation, and the mineralization abilities of DSCs in both in vitro and in vivo conditions. DSCs represent a promising cell source for tissue engineering, especially for tooth, bone, and neural tissue restoration. The purpose of the present review is to summarize the current developments in the major scaffolding approaches as crucial guidelines for tissue engineering using DSCs and compare their effects in tissue and organ regeneration.
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Affiliation(s)
- Cornelia Larissa Granz
- Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster 48149, Germany
| | - Ali Gorji
- Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster 48149, Germany
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11
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Xiang Y, Wang W, Gao Y, Zhang J, Zhang J, Bai Z, Zhang S, Yang Y. Production and Characterization of an Integrated Multi-Layer 3D Printed PLGA/GelMA Scaffold Aimed for Bile Duct Restoration and Detection. Front Bioeng Biotechnol 2020; 8:971. [PMID: 32984274 PMCID: PMC7479063 DOI: 10.3389/fbioe.2020.00971] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Accepted: 07/27/2020] [Indexed: 11/28/2022] Open
Abstract
We successfully fabricated artificial bile duct via 3D printing technique which was composed of poly (lactic-co-glycolic acid) (PLGA) and gelatin methacrylate (GelMA). The PLGA-inner layer provided sufficient strength to support the bile duct contraction, the GelMA-outer layer possessed good biocompatibility to provide a good living environment for the cells. Moreover, IKVAV laminin peptide (Ile-Lys-Val-Ala-Val) and ultrasmall superparamagnetic iron oxide (USPIO) were used to regulate scaffold cell adhesion and magnetic resonance imaging (MRI) detection, respectively. After BMSCs co-culture with IKVAV at a certain concentration, the survival rate and adhesion of BMSCs was increased obviously. Meanwhile, the fabricated scaffold exhibited the tensile modulus in the range of 17.19 - 29.05 MPa and the compressive modulus in the range of 0.042 - 0.066 MPa, which could meet the needs of human implantation. In an animal experiment in vivo pig bile duct regeneration, PLGA/GelMA/IKVAV/USPIO duct conduits could promote bile duct regeneration and enhance cytokeratin 19 (CK19) expression. In summary, the composite bile duct scaffold with excellent MRI imaging function and biocompatibility could be used to develop bioactive artificial bile ducts.
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Affiliation(s)
- Yang Xiang
- Department of Hepatobiliary Surgery, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, China
- Department of Urology Surgery, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, China
| | - Weijia Wang
- School of Metallurgy and Environment, Central South University, Changsha, China
| | - Yuanhui Gao
- Central Laboratory, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, China
| | - Jianquan Zhang
- Department of Hepatobiliary Surgery, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, China
| | - Jing Zhang
- Department of Obstetrics and Gynecology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, China
| | - Zhiming Bai
- Department of Urology Surgery, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, China
| | - Shufang Zhang
- Central Laboratory, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, China
| | - Yijun Yang
- Department of Hepatobiliary Surgery, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, China
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12
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Yao S, He F, Cao Z, Sun Z, Chen Y, Zhao H, Yu X, Wang X, Yang Y, Rosei F, Wang LN. Mesenchymal Stem Cell-Laden Hydrogel Microfibers for Promoting Nerve Fiber Regeneration in Long-Distance Spinal Cord Transection Injury. ACS Biomater Sci Eng 2020; 6:1165-1175. [PMID: 33464837 DOI: 10.1021/acsbiomaterials.9b01557] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Mesenchymal stem cell (MSC)-based regenerative medicine is widely considered as a promising approach for repairing tissue and re-establishing function in spinal cord injury (SCI). However, low survival rate, uncontrollable migration, and differentiation of stem cells after implantation represent major challenges toward the clinical deployment of this approach. In this study, we fabricated three-dimensional MSC-laden microfibers via electrospinning in a rotating cell culture to mimic nerve tissue, control stem cell behavior, and promote integration with the host tissue. The hierarchically aligned fibrin hydrogel was used as the MSC carrier though a rotating method and the aligned fiber structure induced the MSC-aligned adhesion on the surface of the hydrogel to form microscale cell fibers. The MSC-laden microfiber implantation enhanced the donor MSC neural differentiation, encouraged the migration of host neurons into the injury gap and significantly promoted nerve fiber regeneration across the injury site. Abundant GAP-43- and NF-positive nerve fibers were observed to regenerate in the caudal, rostral, and middle sites of the injury position 8 weeks after the surgery. The NF fiber density reached to 29 ± 6 per 0.25 mm2 at the middle site, 82 ± 13 per 0.25 mm2 at the adjacent caudal site, and 70 ± 23 at the adjacent rostral site. Similarly, motor axons labeled with 5-hydroxytryptamine were significantly regenerated in the injury gap, which was 122 ± 22 at the middle injury site that was beneficial for motor function recovery. Most remarkably, the transplantation of MSC-laden microfibers significantly improved electrophysiological expression and re-established limb motor function. These findings highlight the combination of MSCs with microhydrogel fibers, the use of which may become a promising method for MSC implantation and SCI repair.
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Affiliation(s)
- Shenglian Yao
- Beijing Advanced Innovation Center for Materials Genome Engineering, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China.,Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China
| | - Feng He
- Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Zheng Cao
- Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China
| | - Zhenxing Sun
- Department of Neurosurgery, Beijing Tsinghua Changgeng Hospital, School of Clinical Medicine, Tsinghua University, Beijing 100084, China
| | - Yingzhi Chen
- Beijing Advanced Innovation Center for Materials Genome Engineering, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China
| | - He Zhao
- Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China.,Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Xing Yu
- Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Xiumei Wang
- Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China
| | - Yongdong Yang
- Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Federico Rosei
- Beijing Advanced Innovation Center for Materials Genome Engineering, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China.,INRS Centre for Energy, Materials and Telecommunications, 1650 Boul. Lionel Boulet, Varennes J3X 1S2, Canada
| | - Lu-Ning Wang
- Beijing Advanced Innovation Center for Materials Genome Engineering, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China
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Nikolova MP, Chavali MS. Recent advances in biomaterials for 3D scaffolds: A review. Bioact Mater 2019; 4:271-292. [PMID: 31709311 PMCID: PMC6829098 DOI: 10.1016/j.bioactmat.2019.10.005] [Citation(s) in RCA: 463] [Impact Index Per Article: 77.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 10/07/2019] [Accepted: 10/15/2019] [Indexed: 02/06/2023] Open
Abstract
Considering the advantages and disadvantages of biomaterials used for the production of 3D scaffolds for tissue engineering, new strategies for designing advanced functional biomimetic structures have been reviewed. We offer a comprehensive summary of recent trends in development of single- (metal, ceramics and polymers), composite-type and cell-laden scaffolds that in addition to mechanical support, promote simultaneous tissue growth, and deliver different molecules (growth factors, cytokines, bioactive ions, genes, drugs, antibiotics, etc.) or cells with therapeutic or facilitating regeneration effect. The paper briefly focuses on divers 3D bioprinting constructs and the challenges they face. Based on their application in hard and soft tissue engineering, in vitro and in vivo effects triggered by the structural and biological functionalized biomaterials are underlined. The authors discuss the future outlook for the development of bioactive scaffolds that could pave the way for their successful imposing in clinical therapy.
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Affiliation(s)
- Maria P. Nikolova
- Department of Material Science and Technology, University of Ruse “A. Kanchev”, 8 Studentska Str., 7000, Ruse, Bulgaria
| | - Murthy S. Chavali
- Shree Velagapudi Ramakrishna Memorial College (PG Studies, Autonomous), Nagaram, 522268, Guntur District, India
- PG Department of Chemistry, Dharma Appa Rao College, Nuzvid, 521201, Krishna District, India
- MCETRC, Tenali, 522201, Guntur District, Andhra Pradesh, India
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14
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Ashammakhi N, Kim HJ, Ehsanipour A, Bierman RD, Kaarela O, Xue C, Khademhosseini A, Seidlits SK. Regenerative Therapies for Spinal Cord Injury. TISSUE ENGINEERING PART B-REVIEWS 2019; 25:471-491. [PMID: 31452463 DOI: 10.1089/ten.teb.2019.0182] [Citation(s) in RCA: 103] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Spinal cord injury (SCI) is a serious problem that primarily affects younger and middle-aged adults at its onset. To date, no effective regenerative treatment has been developed. Over the last decade, researchers have made significant advances in stem cell technology, biomaterials, nanotechnology, and immune engineering, which may be applied as regenerative therapies for the spinal cord. Although the results of clinical trials using specific cell-based therapies have proven safe, their efficacy has not yet been demonstrated. The pathophysiology of SCI is multifaceted, complex and yet to be fully understood. Thus, combinatorial therapies that simultaneously leverage multiple approaches will likely be required to achieve satisfactory outcomes. Although combinations of biomaterials with pharmacologic agents or cells have been explored, few studies have combined these modalities in a systematic way. For most strategies, clinical translation will be facilitated by the use of minimally invasive therapies, which are the focus of this review. In addition, this review discusses previously explored therapies designed to promote neuroregeneration and neuroprotection after SCI, while highlighting present challenges and future directions. Impact Statement To date there are no effective treatments that can regenerate the spinal cord after injury. Although there have been significant preclinical advances in bioengineering and regenerative medicine over the last decade, these have not translated into effective clinical therapies for spinal cord injury. This review focuses on minimally invasive therapies, providing extensive background as well as updates on recent technological developments and current clinical trials. This review is a comprehensive resource for researchers working towards regenerative therapies for spinal cord injury that will help guide future innovation.
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Affiliation(s)
- Nureddin Ashammakhi
- Division of Plastic Surgery, Department of Surgery, Oulu University, Oulu, Finland.,Center for Minimally Invasive Therapeutics (C-MIT), Los Angeles, California.,California NanoSystems Institute (CNSI), Los Angeles, California.,Department of Radiological Sciences, University of California, Los Angeles, Los Angeles, California.,Department of Bioengineering, University of California, Los Angeles, Los Angeles, California
| | - Han-Jun Kim
- Center for Minimally Invasive Therapeutics (C-MIT), Los Angeles, California.,California NanoSystems Institute (CNSI), Los Angeles, California.,Department of Bioengineering, University of California, Los Angeles, Los Angeles, California
| | | | | | - Outi Kaarela
- Division of Plastic Surgery, Department of Surgery, Oulu University, Oulu, Finland
| | - Chengbin Xue
- Center for Minimally Invasive Therapeutics (C-MIT), Los Angeles, California.,California NanoSystems Institute (CNSI), Los Angeles, California.,Department of Bioengineering, University of California, Los Angeles, Los Angeles, California.,Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, P.R. China.,Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, P.R. China
| | - Ali Khademhosseini
- Center for Minimally Invasive Therapeutics (C-MIT), Los Angeles, California.,California NanoSystems Institute (CNSI), Los Angeles, California.,Department of Radiological Sciences, University of California, Los Angeles, Los Angeles, California.,Department of Bioengineering, University of California, Los Angeles, Los Angeles, California.,Center of Nanotechnology, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Chemical and Biological Engineering, University of California, Los Angeles, California
| | - Stephanie K Seidlits
- Center for Minimally Invasive Therapeutics (C-MIT), Los Angeles, California.,California NanoSystems Institute (CNSI), Los Angeles, California.,Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California.,Broad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, California.,Brain Research Institute, University of California, Los Angeles, Los Angeles, California
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15
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Dental Follicle Cells: Roles in Development and Beyond. Stem Cells Int 2019; 2019:9159605. [PMID: 31636679 PMCID: PMC6766151 DOI: 10.1155/2019/9159605] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Accepted: 08/16/2019] [Indexed: 02/05/2023] Open
Abstract
Dental follicle cells (DFCs) are a group of mesenchymal progenitor cells surrounding the tooth germ, responsible for cementum, periodontal ligament, and alveolar bone formation in tooth development. Cascades of signaling pathways and transcriptional factors in DFCs are involved in directing tooth eruption and tooth root morphogenesis. Substantial researches have been made to decipher multiple aspects of DFCs, including multilineage differentiation, senescence, and immunomodulatory ability. DFCs were proved to be multipotent progenitors with decent amplification, immunosuppressed and acquisition ability. They are able to differentiate into osteoblasts/cementoblasts, adipocytes, neuron-like cells, and so forth. The excellent properties of DFCs facilitated clinical application, as exemplified by bone tissue engineering, tooth root regeneration, and periodontium regeneration. Except for the oral and maxillofacial regeneration, DFCs were also expected to be applied in other tissues such as spinal cord defects (SCD), cardiomyocyte destruction. This article reviewed roles of DFCs in tooth development, their properties, and clinical application potentials, thus providing a novel guidance for tissue engineering.
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16
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Wang D, Wang Y, Tian W, Pan J. Advances of tooth-derived stem cells in neural diseases treatments and nerve tissue regeneration. Cell Prolif 2019; 52:e12572. [PMID: 30714230 PMCID: PMC6536383 DOI: 10.1111/cpr.12572] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 12/05/2018] [Accepted: 12/06/2018] [Indexed: 02/05/2023] Open
Abstract
Nerous system diseases, both central and peripheral, bring an incredible burden onto patients and enormously reduce their quality of life. Currently, there are still no effective treatments to repair nerve lesions that do not have side effects. Stem cell-based therapies, especially those using dental stem cells, bring new hope to neural diseases. Dental stem cells, derived from the neural crest, have many characteristics that are similar to neural cells, indicating that they can be an ideal source of cells for neural regeneration and repair. This review summarizes the neural traits of all the dental cell types, including DPSCs, PDLCs, DFCs, APSCs and their potential applications in nervous system diseases. We have summed up the advantages of dental stem cells in neural repair, such as their neurotrophic and neuroprotective traits, easy harvest and low rejective reaction rate, among others. Taken together, dental stem cells are an ideal cell source for neural tissue regeneration and repair.
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Affiliation(s)
- Dianri Wang
- State Key Laboratory of Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
- Department of Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Yuhao Wang
- State Key Laboratory of Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
- Department of Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Weidong Tian
- State Key Laboratory of Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
- Department of Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Jian Pan
- State Key Laboratory of Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
- Department of Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of StomatologySichuan UniversityChengduChina
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17
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Peng C, Zheng J, Chen D, Zhang X, Deng L, Chen Z, Wu L. Response of hPDLSCs on 3D printed PCL/PLGA composite scaffolds in vitro. Mol Med Rep 2018; 18:1335-1344. [PMID: 29845276 PMCID: PMC6072152 DOI: 10.3892/mmr.2018.9076] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Accepted: 04/13/2018] [Indexed: 12/24/2022] Open
Abstract
Three-dimensional printed (3DP) scaffolds have become an excellent resource in alveolar bone regeneration. However, selecting suitable printable materials remains a challenge. In the present study, 3DP scaffolds were fabricated using three different ratios of poly (ε-caprolactone) (PCL) and poly-lactic-co-glycolic acid (PLGA), which were 0.1PCL/0.9PLGA, 0.5PCL/0.5PLGA and 0.9PCL/0.1PLGA. The surface characteristics and degradative properties of the scaffolds, and the response of human periodontal ligament stem cells (hPDLSCs) on the scaffolds, were assessed to examine the preferable ratio of PCL and PLGA for alveolar bone regeneration. The results demonstrated that the increased proportion of PLGA markedly accelerated the degradation, smoothed the surface and increased the wettability of the hybrid scaffold. Furthermore, the flow cytometry and Cell Counting Kit-8 assay revealed that the adhesion and proliferation of hPDLSCs were markedlyincreased on the 0.5PCL/0.5PLGA and 0.1PCL/0.9PLGA scaffolds. Additionally, the alkaline phosphatase activity detection and reverse-transcription quantitative polymerase chain reaction demonstrated that the hPDLSCs on the 0.5PCL/0.5PLGA scaffold exhibited the best osteogenic capacity. Consequently, PCL/PLGA composite scaffolds may represent a candidate focus for future bone regeneration studies, and the 0.5PCL/0.5PLGA scaffold demonstrated the best bio-response from the hPDLSCs.
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Affiliation(s)
- Caixia Peng
- Department of Orthodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Jinxuan Zheng
- Department of Orthodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Dongru Chen
- Department of Orthodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Xueqin Zhang
- Department of Orthodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Lidi Deng
- Department of Orthodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Zhengyuan Chen
- Department of Orthodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Liping Wu
- Department of Orthodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China
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18
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Abstract
Spinal cord injury (SCI) represents one of the most complicated and heterogeneous pathological processes of central nervous system (CNS) impairments, which is still beyond functional regeneration. Transplantation of mesenchymal stem cells (MSCs) has been shown to promote the repair of the injured spinal cord tissues in animal models, and therefore, there is much interest in the clinical use of these cells. However, many questions which are essential to improve the therapy effects remain unanswered. For instance, the functional roles and related molecular regulatory mechanisms of MSCs in vivo are not yet completely determined. It is important for transplanted cells to migrate into the injured tissue, to survive and undergo neural differentiation, or to play neural protection roles by various mechanisms after SCI. In this review, we will focus on some of the recent knowledge about the biological behavior and function of MSCs in SCI. Meanwhile, we highlight the function of biomaterials to direct the behavior of MSCs based on our series of work on silk fibroin biomaterials and attempt to emphasize combinational strategies such as tissue engineering for functional improvement of SCI.
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19
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Yang C, Li X, Sun L, Guo W, Tian W. Potential of human dental stem cells in repairing the complete transection of rat spinal cord. J Neural Eng 2017; 14:026005. [PMID: 28085005 DOI: 10.1088/1741-2552/aa596b] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE The adult spinal cord of mammals contains a certain amount of neural precursor cells, but these endogenous cells have a limited capacity for replacement of lost cells after spinal cord injury. The exogenous stem cells transplantation has become a therapeutic strategy for spinal cord repairing because of their immunomodulatory and differentiation capacity. In addition, dental stem cells originating from the cranial neural crest might be candidate cell sources for neural engineering. APPROACH Human dental follicle stem cells (DFSCs), stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) were isolated and identified in vitro, then green GFP-labeled stem cells with pellets were transplanted into completely transected spinal cord. The functional recovery of rats and multiple neuro-regenerative mechanisms were explored. MAIN RESULTS The dental stem cells, especially DFSCs, demonstrated the potential in repairing the completely transected spinal cord and promote functional recovery after injury. The major involved mechanisms were speculated below: First, dental stem cells inhibited the expression of interleukin-1β to reduce the inflammatory response; second, they inhibited the expression of ras homolog gene family member A (RhoA) to promote neurite regeneration; third, they inhibited the sulfonylurea receptor1 (SUR-1) expression to reduce progressive hemorrhagic necrosis; lastly, parts of the transplanted cells survived and differentiated into mature neurons and oligodendrocytes but not astrocyte, which is beneficial for promoting axons growth. SIGNIFICANCE Dental stem cells presented remarkable tissue regenerative capability after spinal cord injury through immunomodulatory, differentiation and protection capacity.
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Affiliation(s)
- Chao Yang
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China
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20
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Salem N, Salem MY, Elmaghrabi MM, Elawady MA, Elawady MA, Sabry D, Shamaa A, Elkasapy AHH, Ibrhim N, Elamir A. Does vitamin C have the ability to augment the therapeutic effect of bone marrow-derived mesenchymal stem cells on spinal cord injury? Neural Regen Res 2017; 12:2050-2058. [PMID: 29323045 PMCID: PMC5784354 DOI: 10.4103/1673-5374.221163] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Methylprednisolone (MP) is currently the only drug confirmed to exhibit a neuroprotective effect on acute spinal cord injury (SCI). Vitamin C (VC) is a natural water-soluble antioxidant that exerts neuroprotective effects through eliminating free radical damage to nerve cells. Bone marrow mesenchymal stem cells (BMMSCs), as multipotent stem cells, are promising candidates in SCI repair. To evaluate the therapeutic effects of MP, VC and BMMSCs on traumatic SCI, 80 adult male rats were randomly divided into seven groups: control, SCI (SCI induction by weight-drop method), MP (SCI induction, followed by administration of 30 mg/kg MP via the tail vein, once every other 6 hours, for five times), VC (SCI induction, followed by intraperitoneal administration of 100 mg/kg VC once a day, for 28 days), MP + VC (SCI induction, followed by administration of MP and VC as the former), BMMSCs (SCI induction, followed by injection of 3 × 106 BMMSCs at the injury site), and BMMSCs + VC (SCI induction, followed by BMMSCs injection and VC administration as the former). Locomotor recovery was assessed using the Basso Mouse Scale. Injured spinal cord tissue was evaluated using hematoxylin-eosin staining and immunohistochemical staining. Expression of transforming growth factor-beta, tumor necrosis factor-alpha, and matrix metalloproteinase-2 genes was determined using real-time quantitative PCR. BMMSCs intervention better promoted recovery of nerve function of rats with SCI, mitigated nerve cell damage, and decreased expression of transforming growth factor-beta, tumor necrosis factor-alpha, and matrix metalloproteinase-2 genes than MP and/or VC. More importantly, BMMSCs in combination with VC induced more obvious improvements. These results suggest that VC can enhance the neuroprotective effects of BMMSCs against SCI.
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Affiliation(s)
- Nesrine Salem
- Department of Histology and Cell Biology, Faculty of Medicine, Banha University, Banha, Egypt
| | - Mohamed Y Salem
- Department of Histology and Cell Biology, Faculty of Medicine, Banha University, Banha, Egypt
| | | | - Moataz A Elawady
- Department of Neurosurgery, Faculty of Medicine, Banha University, Banha, Egypt
| | - Mona A Elawady
- Department of Community Medicine, Faculty of Medicine, Banha University, Banha, Egypt
| | - Dina Sabry
- Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Ashraf Shamaa
- Department of Surgery and Radiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | | | - Noha Ibrhim
- Department of Medical Physiology, Faculty of Medicine, Banha University, Banha, Egypt
| | - Azza Elamir
- Department of Medical Biochemistry, Faculty of Medicine, El Fayoum University, Egyptian, Egypt
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21
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The Neurovascular Properties of Dental Stem Cells and Their Importance in Dental Tissue Engineering. Stem Cells Int 2016; 2016:9762871. [PMID: 27688777 PMCID: PMC5027319 DOI: 10.1155/2016/9762871] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Accepted: 08/01/2016] [Indexed: 12/16/2022] Open
Abstract
Within the field of tissue engineering, natural tissues are reconstructed by combining growth factors, stem cells, and different biomaterials to serve as a scaffold for novel tissue growth. As adequate vascularization and innervation are essential components for the viability of regenerated tissues, there is a high need for easily accessible stem cells that are capable of supporting these functions. Within the human tooth and its surrounding tissues, different stem cell populations can be distinguished, such as dental pulp stem cells, stem cells from human deciduous teeth, stem cells from the apical papilla, dental follicle stem cells, and periodontal ligament stem cells. Given their straightforward and relatively easy isolation from extracted third molars, dental stem cells (DSCs) have become an attractive source of mesenchymal-like stem cells. Over the past decade, there have been numerous studies supporting the angiogenic, neuroprotective, and neurotrophic effects of the DSC secretome. Together with their ability to differentiate into endothelial cells and neural cell types, this makes DSCs suitable candidates for dental tissue engineering and nerve injury repair.
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22
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Cryopreservation and Banking of Dental Stem Cells. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2016; 951:199-235. [DOI: 10.1007/978-3-319-45457-3_17] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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