|
1
|
Liu M, Lu Y, Sun F, Li Y, Wu J, Zou Q. The Nerve-Induced Adipose Stem Cells Promote Nerve Repair in Stress Urinary Incontinence by Regulating Schwann Cell Repair Phenotype Conversion Through Activation of the Notch Pathway. Mol Neurobiol 2025; 62:7330-7344. [PMID: 39881114 DOI: 10.1007/s12035-025-04704-z] [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: 06/10/2024] [Accepted: 01/13/2025] [Indexed: 01/31/2025]
Abstract
Stress urinary incontinence (SUI) currently lacks effective treatment options, and the restoration of neurological function remains a major challenge, with unmet clinical needs. Research has indicated that adipose-derived stem cells (ADSCs) can be induced to differentiate into neural-induced adipose-derived stem cells (NI-ADSCs) under specific inductive conditions, exhibiting excellent neuroregenerative capabilities. ADSCs were obtained from female SD rats and induced into NI-ADSCs. In vitro, NI-ADSCs were co-cultured with Schwann cells (SCs) to investigate their effects on SC proliferation and repair phenotype transition and further explore its underlying mechanism. In vivo, a rat model of SUI was established using a bilateral pudendal nerve transection method. NI-ADSCs were injected into the urethral sphincter to evaluate their effects on urodynamics, muscle angiogenesis, and neural repair in SUI rats, while also exploring the mechanisms of neural repair. This study used EGF, FGF, and B27 to induce ADSCs into NI-ADSCs expressing neural induction markers (MAP, Nestin, and PAX6). In vitro experiments found no significant difference in the proliferation of L6 and RSC96 between NI-ADSCs and ADSCs (p > 0.05). However, when co-cultured with NI-ADSCs, SCs showed upregulated expression of repair-related phenotypic markers (BDNF, GDNF, and GFAP). In this phenotypic transformation process, the expression of Notch-related pathway proteins (Notch1, NICD, and Hes1) was increased, and the use of DAPT (a Notch pathway inhibitor) could suppress the SC repair phenotype transformation. In vivo, experiments revealed that intraurethral injection of NI-ADSCs significantly promoted the expression of neural marker (S100β) and demyelination markers (GFAP) and urodynamic recovery in SUI rats, while DAPT inhibited its neural repair effect. In summary, our study demonstrates that NI-ADSCs can promote nerve regeneration by promoting and maintaining the repair-related phenotype of SCs. The underlying mechanism may be related to the activation of the Notch signaling pathway.
Collapse
Affiliation(s)
- Ming Liu
- Department of Urology, Yantai Yuhuangding Hospital, Qingdao University, No. 20 East Yuhuangding Road, Yantai, 264000, Shandong, China
- Second Clinical Medical College, Binzhou Medical University, Yantai, 264003, Shandong, China
| | - Youyi Lu
- Department of Urology, Yantai Yuhuangding Hospital, Qingdao University, No. 20 East Yuhuangding Road, Yantai, 264000, Shandong, China
| | - Fengze Sun
- Department of Urology, Yantai Yuhuangding Hospital, Qingdao University, No. 20 East Yuhuangding Road, Yantai, 264000, Shandong, China
| | - Yongwei Li
- Department of Urology, Yantai Yuhuangding Hospital, Qingdao University, No. 20 East Yuhuangding Road, Yantai, 264000, Shandong, China
| | - Jitao Wu
- Department of Urology, Yantai Yuhuangding Hospital, Qingdao University, No. 20 East Yuhuangding Road, Yantai, 264000, Shandong, China.
| | - Qingsong Zou
- Department of Urology, Yantai Yuhuangding Hospital, Qingdao University, No. 20 East Yuhuangding Road, Yantai, 264000, Shandong, China.
| |
Collapse
|
|
2
|
Pi HJ, Huang B, Yuan Q, Jing JJ. Neural regulation of mesenchymal stem cells in craniofacial bone: development, homeostasis and repair. Front Physiol 2024; 15:1423539. [PMID: 39135707 PMCID: PMC11318092 DOI: 10.3389/fphys.2024.1423539] [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: 04/26/2024] [Accepted: 07/15/2024] [Indexed: 08/15/2024] Open
Abstract
Mesenchymal stem cells endow various functions, including proliferation, multipotency, migration, etc. Craniofacial bones originate from the cranial neural crest and are developed mainly through intramembranous ossification, which are different from long bones. There are varied mesenchymal stem cells existing in the craniofacial bone, including Gli1 + cells, Axin2 + cells, Prx1 + cells, etc. Nerves distributed in craniofacial area are also derived from the neural crest, and the trigeminal nerve is the major sensory nerve in craniofacial area. The nerves and the skeleton are tightly linked spatially, and the skeleton is broadly innervated by sensory and sympathetic nerves, which also participate in bone development, homeostasis and healing process. In this review, we summarize mesenchymal stem cells located in craniofacial bone or, to be more specific, in jaws, temporomandibular joint and cranial sutures. Then we discuss the research advance concerning neural regulation of mesenchymal stem cells in craniofacial bone, mainly focused on development, homeostasis and repair. Discovery of neural regulation of mesenchymal stem cells may assist in treatment in the craniofacial bone diseases or injuries.
Collapse
Affiliation(s)
| | | | - Quan Yuan
- *Correspondence: Quan Yuan, ; Jun-Jun Jing,
| | | |
Collapse
|
|
3
|
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.
Collapse
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.
| |
Collapse
|
|
4
|
Xu S, Wei J, Liu Y, Zhang L, Duan M, Li J, Niu Z, Pu X, Huang M, Chen H, Zhou X, Xie J. PDGF-AA guides cell crosstalk between human dental pulp stem cells in vitro via the PDGFR-α/PI3K/Akt axis. Int Endod J 2024; 57:549-565. [PMID: 38332717 DOI: 10.1111/iej.14038] [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: 09/26/2023] [Revised: 01/24/2024] [Accepted: 01/25/2024] [Indexed: 02/10/2024]
Abstract
AIM To explore the influence of PDGF-AA on cell communication between human dental pulp stem cells (DPSCs) by characterizing gap junction intercellular communication (GJIC) and its potential biomechanical mechanism. METHODOLOGY Quantitative real-time PCR was used to measure connexin family member expression in DPSCs. Cell migration and CCK-8 assays were utilized to examine the influence of PDGF-AA on DPSC migration and proliferation. A scrape loading/dye transfer assay was applied to evaluate GJIC triggered by PDGF-AA, a PI3K/Akt signalling pathway blocker (LY294002) and a PDGFR-α blocker (AG1296). Western blotting and immunofluorescence were used to test the expression and distribution of the Cx43 and p-Akt proteins in DPSCs. Scanning electron microscopy (SEM) and immunofluorescence were used to observe the morphology of GJIC in DPSCs. RESULTS PDGF-AA promoted gap junction formation and intercellular communication between human dental pulp stem cells. PDGF-AA upregulates the expression of Cx43 to enhance gap junction formation and intercellular communication. PDGF-AA binds to PDGFR-α and activates PI3K/Akt signalling to regulate cell communication. CONCLUSIONS This research demonstrated that PDGF-AA can enhance Cx43-mediated GJIC in DPSCs via the PDGFR-α/PI3K/Akt axis, which provides new cues for dental pulp regeneration from the perspective of intercellular communication.
Collapse
Affiliation(s)
- Siqun Xu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Jieya Wei
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Yang Liu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Li Zhang
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Mengmeng Duan
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Jiazhou Li
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Zhixing Niu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Xiaohua Pu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Minglei Huang
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Hao Chen
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Xuedong Zhou
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Jing Xie
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| |
Collapse
|
|
5
|
Cabaña-Muñoz ME, Pelaz Fernández MJ, Parmigiani-Cabaña JM, Parmigiani-Izquierdo JM, Merino JJ. Adult Mesenchymal Stem Cells from Oral Cavity and Surrounding Areas: Types and Biomedical Applications. Pharmaceutics 2023; 15:2109. [PMID: 37631323 PMCID: PMC10459416 DOI: 10.3390/pharmaceutics15082109] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 07/28/2023] [Accepted: 08/02/2023] [Indexed: 08/27/2023] Open
Abstract
Adult mesenchymal stem cells are those obtained from the conformation of dental structures (DMSC), such as deciduous and permanent teeth and other surrounding tissues. Background: The self-renewal and differentiation capacities of these adult stem cells allow for great clinical potential. Because DMSC are cells of ectomesenchymal origin, they reveal a high capacity for complete regeneration of dental pulp, periodontal tissue, and other biomedical applications; their differentiation into other types of cells promotes repair in muscle tissue, cardiac, pancreatic, nervous, bone, cartilage, skin, and corneal tissues, among others, with a high predictability of success. Therefore, stem and progenitor cells, with their exosomes of dental origin and surrounding areas in the oral cavity due to their plasticity, are considered a fundamental pillar in medicine and regenerative dentistry. Tissue engineering (MSCs, scaffolds, and bioactive molecules) sustains and induces its multipotent and immunomodulatory effects. It is of vital importance to guarantee the safety and efficacy of the procedures designed for patients, and for this purpose, more clinical trials are needed to increase the efficacy of several pathologies. Conclusion: From a bioethical and transcendental anthropological point of view, the human person as a unique being facilitates better clinical and personalized therapy, given the higher prevalence of dental and chronic systemic diseases.
Collapse
Affiliation(s)
- María Eugenia Cabaña-Muñoz
- CIROM—Centro de Rehabilitación Oral Multidisciplinaria, 30001 Murcia, Spain; (M.E.C.-M.); (J.M.P.-C.); (J.M.P.-I.)
| | | | - José María Parmigiani-Cabaña
- CIROM—Centro de Rehabilitación Oral Multidisciplinaria, 30001 Murcia, Spain; (M.E.C.-M.); (J.M.P.-C.); (J.M.P.-I.)
| | | | - José Joaquín Merino
- Departamento de Farmacología, Farmacognosia y Botánica, Facultad de Farmacia, Universidad Complutense de Madrid (U.C.M), 28040 Madrid, Spain
| |
Collapse
|
|
6
|
Uribe-Etxebarria V, Pineda JR, García-Gallastegi P, Agliano A, Unda F, Ibarretxe G. Notch and Wnt Signaling Modulation to Enhance DPSC Stemness and Therapeutic Potential. Int J Mol Sci 2023; 24:ijms24087389. [PMID: 37108549 PMCID: PMC10138690 DOI: 10.3390/ijms24087389] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/16/2023] [Accepted: 04/16/2023] [Indexed: 04/29/2023] Open
Abstract
The Dental Pulp of permanent human teeth is home to stem cells with remarkable multilineage differentiation ability: human Dental Pulp Stem Cells (DPSCs). These cells display a very notorious expression of pluripotency core factors, and the ability to give rise to mature cell lineages belonging to the three embryonic layers. For these reasons, several researchers in the field have long considered human DPSCs as pluripotent-like cells. Notably, some signaling pathways such as Notch and Wnt contribute to maintaining the stemness of these cells through a complex network involving metabolic and epigenetic regulatory mechanisms. The use of recombinant proteins and selective pharmacological modulators of Notch and Wnt pathways, together with serum-free media and appropriate scaffolds that allow the maintenance of the non-differentiated state of hDPSC cultures could be an interesting approach to optimize the potency of these stem cells, without a need for genetic modification. In this review, we describe and integrate findings that shed light on the mechanisms responsible for stemness maintenance of hDPSCs, and how these are regulated by Notch/Wnt activation, drawing some interesting parallelisms with pluripotent stem cells. We summarize previous work on the stem cell field that includes interactions between epigenetics, metabolic regulations, and pluripotency core factor expression in hDPSCs and other stem cell types.
Collapse
Affiliation(s)
| | - Jose Ramon Pineda
- Cell Biology and Histology Department, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain
- Achucarro Basque Center for Neuroscience Fundazioa Leioa, Sede Building, 3rd Floor, 48940 Leioa, Spain
| | - Patricia García-Gallastegi
- Physiology Department, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain
| | - Alice Agliano
- Division of Radiotherapy and Imaging, Cancer Research UK Cancer Imaging Centre, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London SW7 3RP, UK
- Department of Materials and Department of Bioengineering, Institute of Biomedical Engineering, Imperial College London, Exhibition Road, London SW7 2AZ, UK
| | - Fernando Unda
- Cell Biology and Histology Department, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain
| | - Gaskon Ibarretxe
- Cell Biology and Histology Department, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain
| |
Collapse
|
|
7
|
Dynamic expression of Mage-D1 in rat dental germs and potential role in mineralization of ectomesenchymal stem cells. Sci Rep 2022; 12:22615. [PMID: 36585447 PMCID: PMC9803661 DOI: 10.1038/s41598-022-27197-5] [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: 01/29/2022] [Accepted: 12/28/2022] [Indexed: 12/31/2022] Open
Abstract
Mage-D1 (MAGE family member D1) is involved in a variety of cell biological effects. Recent studies have shown that Mage-D1 is closely related to tooth development, but its specific regulatory mechanism is unclear. The purpose of this study was to investigate the expression pattern of Mage-D1 in rat dental germ development and its differential mineralization ability to ectomesenchymal stem cells (EMSCs), and to explore its potential mechanism. Results showed that the expression of Mage-D1 during rat dental germ development was temporally and spatially specific. Mage-D1 promotes the proliferation ability of EMSCs but inhibits their migration ability. Under induction by mineralized culture medium, Mage-D1 promotes osteogenesis and tooth-forming ability. Furthermore, the expression pattern of Mage-D1 at E19.5 d rat dental germ is similar to p75 neurotrophin receptor (p75NTR), distal-less homeobox 1 (Dlx1) and msh homeobox 1 (Msx1). In addition, Mage-D1 is binding to p75NTR, Dlx1, and Msx1 in vitro. These findings indicate that Mage-D1 is play an important regulatory role in normal mineralization of teeth. p75NTR, Dlx1, and Msx1 seem to be closely related to the underlying mechanism of Mage-D1 action.
Collapse
|
|
8
|
Song W, Bo X, Ma X, Hou K, Li D, Geng W, Zeng J. Craniomaxillofacial derived bone marrow mesenchymal stem/stromal cells (BMSCs) for craniomaxillofacial bone tissue engineering: A literature review. JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2022; 123:e650-e659. [PMID: 35691558 DOI: 10.1016/j.jormas.2022.06.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 04/06/2022] [Accepted: 06/07/2022] [Indexed: 11/20/2022]
Abstract
Craniomaxillofacial bone defects seriously affect the appearance, function, and psychological status of patients. Traditional autologous bone grafting is very challenging due to the limited sources of bone tissue, excessive surgical trauma, and high incidence of related complications. Craniomaxillofacial bone tissue engineering (BTE) strategies based on bone marrow mesenchymal stem cells (BMSCs) are emerging as an alternative. Craniomaxillofacial BMSCs (C-BMSCs) are homologous to craniomaxillofacial bones, which develop from the mesoderm and neural crest. This article aims to compare the differences in osteogenesis, angiogenesis, and immune regulation of C-BMSCs and other sources of BMSCs, and propose ideas and strategies such as 3D printing and mechanotherapy to completely harness the characteristics of C-BMSCs. In conclusion, C-BSMCs are a promising source of stem cells for the repair and reconstruction of craniomaxillofacial bone defects, and more attention should be paid to accelerating their basic research and clinical practices.
Collapse
Affiliation(s)
- Wenpeng Song
- Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China
| | - Xiaowen Bo
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Xiaohan Ma
- Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China
| | - Kegui Hou
- Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China; Department of Stomatology, Shunyi District Hospital affiliated to Capital Medical University, Beijing, China
| | - Dan Li
- Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China
| | - Wei Geng
- Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China
| | - Jianyu Zeng
- Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China.
| |
Collapse
|
|
9
|
Pineda JR, Polo Y, Pardo-Rodríguez B, Luzuriaga J, Uribe-Etxebarria V, García-Gallastegui P, Sarasua JR, Larrañaga A, Ibarretxe G. In vitro preparation of human Dental Pulp Stem Cell grafts with biodegradable polymer scaffolds for nerve tissue engineering. Methods Cell Biol 2022; 170:147-167. [PMID: 35811097 DOI: 10.1016/bs.mcb.2022.02.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Human Dental Pulp Stem Cells (hDPSCs) are one of the most promising stem cell sources for tissue engineering and regeneration, due to their extraordinary multi-lineage differentiation ability, ease of extraction from biological waste in dental clinics, safe non-tumorigenic phenotype, immune-tolerance upon in vivo transplantation, and great possibilities of application in autologous tissue reconstruction. The in vitro manipulation of hDPSCs paves the way for drug screening and tailor-made regeneration of damaged tissues, in the context of personalized medicine. The neural crest phenotype of these stem cells gives them the capacity to differentiate to a large variety of cell types, including neural-lineage cells. In this chapter, we describe various culture methods to generate different cellular phenotypes from hDPSCs, which can not only grow as mesenchymal-like plastic adherent cells, but also as non-adherent neurogenic dentospheres in serum-free medium. Floating dentospheres can be used to generate large populations of mature neuronal and glial marker expressing cells, which may be cultured over a substrate of nanopatterned scaffold based on biodegradable poly(lactide-co-caprolactone) (PLCL) to induce a controlled alignment of neurites and cell migration, to generate in vivo biocompatible constructs for nerve tissue bioengineering.
Collapse
Affiliation(s)
- 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.
| | - Yurena Polo
- Polimerbio SL, Donostia-San Sebastián, 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
| | - 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 Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
| | - Verónica Uribe-Etxebarria
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
| | - Patricia García-Gallastegui
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
| | - José Ramón Sarasua
- Polimerbio SL, Donostia-San Sebastián, 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.
| | - 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.
| | - Gaskon Ibarretxe
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain.
| |
Collapse
|
|
10
|
Dave JR, Chandekar SS, Behera S, Desai KU, Salve PM, Sapkal NB, Mhaske ST, Dewle AM, Pokare PS, Page M, Jog A, Chivte PA, Srivastava RK, Tomar GB. Human gingival mesenchymal stem cells retain their growth and immunomodulatory characteristics independent of donor age. SCIENCE ADVANCES 2022; 8:eabm6504. [PMID: 35749495 PMCID: PMC9232118 DOI: 10.1126/sciadv.abm6504] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 05/06/2022] [Indexed: 05/28/2023]
Abstract
Aging has been reported to deteriorate the quantity and quality of mesenchymal stem cells (MSCs), which affect their therapeutic use in regenerative medicine. A dearth of age-related stem cell research further restricts their clinical applications. The present study explores the possibility of using MSCs derived from human gingival tissues (GMSCs) for studying their ex vivo growth characteristics and differentiation potential with respect to donor age. GMSCs displayed decreased in vitro adipogenesis and in vitro and in vivo osteogenesis with age, but in vitro neurogenesis remained unaffected. An increased expression of p53 and SIRT1 with donor age was correlated to their ability of eliminating tumorigenic events through apoptosis or autophagy, respectively. Irrespective of donor age, GMSCs displayed effective immunoregulation and regenerative potential in a mouse model of LPS-induced acute lung injury. Thus, we suggest the potential of GMSCs for designing cell-based immunomodulatory therapeutic approaches and their further extrapolation for acute inflammatory conditions such as acute respiratory distress syndrome and COVID-19.
Collapse
Affiliation(s)
- Jay R. Dave
- Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune, 411007 Maharashtra, India
| | - Sayali S. Chandekar
- Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune, 411007 Maharashtra, India
| | - Shubhanath Behera
- National Centre for Cell Science, Savitribai Phule Pune University Campus, Pune, 411007 Maharashtra, India
| | - Kaushik U. Desai
- Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune, 411007 Maharashtra, India
| | - Pradnya M. Salve
- Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune, 411007 Maharashtra, India
| | - Neha B. Sapkal
- Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune, 411007 Maharashtra, India
| | - Suhas T. Mhaske
- Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune, 411007 Maharashtra, India
| | - Ankush M. Dewle
- Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune, 411007 Maharashtra, India
| | - Parag S. Pokare
- Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune, 411007 Maharashtra, India
| | - Megha Page
- Department of Dentistry, Deenanath Mangeshkar Hospital and Research Centre, Pune, 411004 Maharashtra, India
| | - Ajay Jog
- Department of Dentistry, Deenanath Mangeshkar Hospital and Research Centre, Pune, 411004 Maharashtra, India
| | - Pankaj A. Chivte
- Saraswati Danwantri Dental College and Hospital, Parbhani, 431401 Maharashtra, India
| | - Rupesh K. Srivastava
- Department of Biotechnology, All India Institute of Medical Science, New Delhi 110029, India
| | - Geetanjali B. Tomar
- Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune, 411007 Maharashtra, India
| |
Collapse
|
|
11
|
Yan Y, Yao R, Zhao J, Chen K, Duan L, Wang T, Zhang S, Guan J, Zheng Z, Wang X, Liu Z, Li Y, Li G. Implantable nerve guidance conduits: Material combinations, multi-functional strategies and advanced engineering innovations. Bioact Mater 2022; 11:57-76. [PMID: 34938913 PMCID: PMC8665266 DOI: 10.1016/j.bioactmat.2021.09.030] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 09/17/2021] [Accepted: 09/26/2021] [Indexed: 01/15/2023] Open
Abstract
Nerve guidance conduits (NGCs) have attracted much attention due to their great necessity and applicability in clinical use for the peripheral nerve repair. Great efforts in recent years have been devoted to the development of high-performance NGCs using various materials and strategies. The present review provides a comprehensive overview of progress in the material innovation, structural design, advanced engineering technologies and multi functionalization of state-of-the-art nerve guidance conduits NGCs. Abundant advanced engineering technologies including extrusion-based system, laser-based system, and novel textile forming techniques in terms of weaving, knitting, braiding, and electrospinning techniques were also analyzed in detail. Findings arising from this review indicate that the structural mimetic NGCs combined with natural and synthetic materials using advanced manufacturing technologies can make full use of their complementary advantages, acquiring better biomechanical properties, chemical stability and biocompatibility. Finally, the existing challenges and future opportunities of NGCs were put forward aiming for further research and applications of NGCs.
Collapse
Affiliation(s)
- Yixin Yan
- National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123, China
- Department of Materials, University of Manchester, Oxford Road, Manchester, M13 9PL, UK
| | - Ruotong Yao
- National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123, China
| | - Jingyuan Zhao
- National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123, China
| | - Kaili Chen
- Department of Materials, Imperial College London, SW7 2AZ, UK
| | - Lirong Duan
- National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123, China
| | - Tian Wang
- Wilson College of Textiles, North Carolina State University, Raleigh, 27695, USA
| | - Shujun Zhang
- Research Centre of Printed Flexible Electronics, School of Materials Science and Engineering, Harbin Institute of Technology, Shenzhen, 518055, China
| | - Jinping Guan
- National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123, China
| | - Zhaozhu Zheng
- National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123, China
| | - Xiaoqin Wang
- National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123, China
| | - Zekun Liu
- Department of Materials, University of Manchester, Oxford Road, Manchester, M13 9PL, UK
| | - Yi Li
- Department of Materials, University of Manchester, Oxford Road, Manchester, M13 9PL, UK
| | - Gang Li
- National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123, China
| |
Collapse
|
|
12
|
Guo L, Zou Z, Smeets R, Kluwe L, Hartjen P, Gosau M, Henningsen A. Attachment and Osteogenic Potential of Dental Pulp Stem Cells on Non-Thermal Plasma and UV Light Treated Titanium, Zirconia and Modified PEEK Surfaces. MATERIALS 2022; 15:ma15062225. [PMID: 35329678 PMCID: PMC8950369 DOI: 10.3390/ma15062225] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 02/21/2022] [Accepted: 02/25/2022] [Indexed: 11/16/2022]
Abstract
Ultraviolet (UV) light and non-thermal plasma (NTP) treatment are chairside methods that can efficiently improve the biological aging of implant material surfaces caused by customary storage. However, the behaviors of stem cells on these treated surfaces of the implant are still unclear. This study aimed to investigate the effects of UV light and NTP treated surfaces of titanium, zirconia and modified polyetheretherketone (PEEK, BioHPP) on the attachment and osteogenic potential of human dental pulp stem cells (DPSCs) in vitro. Machined disks were treated using UV light and argon or oxygen NTP for 12 min each. Untreated disks were set as controls. DPSCs were cultured from the wisdom teeth of adults that gave informed consent. After 24 h of incubation, the attachment and viability of cells on surfaces were assessed. Cells were further osteogenically induced, alkaline phosphatase (ALP) activity was detected via a p-Nitrophenyl phosphate assay (day 14 and 21) and mineralization degree was measured using a Calcium Assay kit (day 21). UV light and NTP treated titanium, zirconia and BioHPP surfaces improved the early attachment and viability of DPSCs. ALP activity and mineralization degree of osteoinductive DPSCs were significantly increased on UV light and NTP treated surfaces of titanium, zirconia and also oxygen plasma treated Bio-HPP (p < 0.05). In conclusion, UV light and NTP treatments may improve the attachment of DPSCs on titanium, zirconia and BioHPP surfaces. Osteogenic differentiation of DPSCs can be enhanced on UV light and NTP treated surfaces of titanium and zirconia, as well as on oxygen plasma treated Bio-HPP.
Collapse
Affiliation(s)
- Linna Guo
- Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha 410011, China
- Department of Oral and Maxillofacial Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany; (Z.Z.); (R.S.); (L.K.); (P.H.); (M.G.)
- Division Regenerative Orofacial Medicine, Department of Oral and Maxillofacial Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany;
- Correspondence:
| | - Ziang Zou
- Department of Oral and Maxillofacial Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany; (Z.Z.); (R.S.); (L.K.); (P.H.); (M.G.)
- Department of Gynecology and Obstetrics, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Ralf Smeets
- Department of Oral and Maxillofacial Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany; (Z.Z.); (R.S.); (L.K.); (P.H.); (M.G.)
- Division Regenerative Orofacial Medicine, Department of Oral and Maxillofacial Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany;
| | - Lan Kluwe
- Department of Oral and Maxillofacial Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany; (Z.Z.); (R.S.); (L.K.); (P.H.); (M.G.)
| | - Philip Hartjen
- Department of Oral and Maxillofacial Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany; (Z.Z.); (R.S.); (L.K.); (P.H.); (M.G.)
- Division Regenerative Orofacial Medicine, Department of Oral and Maxillofacial Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany;
| | - Martin Gosau
- Department of Oral and Maxillofacial Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany; (Z.Z.); (R.S.); (L.K.); (P.H.); (M.G.)
| | - Anders Henningsen
- Division Regenerative Orofacial Medicine, Department of Oral and Maxillofacial Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany;
- Private Practice ELBE MKG, 22587 Hamburg, Germany
| |
Collapse
|
|
13
|
Human Sex Matters: Y-Linked Lysine Demethylase 5D Drives Accelerated Male Craniofacial Osteogenic Differentiation. Cells 2022; 11:cells11050823. [PMID: 35269444 PMCID: PMC8909072 DOI: 10.3390/cells11050823] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 02/16/2022] [Accepted: 02/24/2022] [Indexed: 12/12/2022] Open
Abstract
Female sex is increasingly associated with a loss of bone mass during aging and an increased risk of developing nonunion fractures. Hormonal factors and cell-intrinsic mechanisms are suggested to drive these sexual dimorphisms, although underlying molecular mechanisms are still a matter of debate. Here, we observed a decreased capacity of calvarial bone recovery in female rats and a profound sexually dimorphic osteogenic differentiation in human adult neural crest-derived stem cells (NCSCs). Next to an elevated expression of pro-osteogenic regulators, global transcriptomics revealed Lysine Demethylase 5D (KDM5D) to be highly upregulated in differentiating male NCSCs. Loss of function by siRNA or pharmacological inhibition of KDM5D significantly reduced the osteogenic differentiation capacity of male NCSCs. In summary, we demonstrated craniofacial osteogenic differentiation to be sexually dimorphic with the expression of KDM5D as a prerequisite for accelerated male osteogenic differentiation, emphasizing the analysis of sex-specific differences as a crucial parameter for treating bone defects.
Collapse
|
|
14
|
Argaez-Sosa AA, Rodas-Junco BA, Carrillo-Cocom LM, Rojas-Herrera RA, Coral-Sosa A, Aguilar-Ayala FJ, Aguilar-Pérez D, Nic-Can GI. Higher Expression of DNA (de)methylation-Related Genes Reduces Adipogenicity in Dental Pulp Stem Cells. Front Cell Dev Biol 2022; 10:791667. [PMID: 35281092 PMCID: PMC8907981 DOI: 10.3389/fcell.2022.791667] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 02/08/2022] [Indexed: 12/17/2022] Open
Abstract
Obesity is a significant health concern that has reached alarming proportions worldwide. The overconsumption of high-energy foods may cause metabolic dysfunction and promote the generation of new adipocytes by contributing to several obesity-related diseases. Such concerns demand a deeper understanding of the origin of adipocytes if we want to develop new therapeutic approaches. Recent findings indicate that adipocyte development is facilitated by tight epigenetic reprogramming, which is required to activate the gene program to change the fate of mesenchymal stem cells (MSCs) into mature adipocytes. Like adipose tissue, different tissues are also potential sources of adipocyte-generating MSCs, so it is interesting to explore whether the epigenetic mechanisms of adipogenic differentiation vary from one depot to another. To investigate how DNA methylation (an epigenetic mark that plays an essential role in controlling transcription and cellular differentiation) contributes to adipogenic potential, dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PLSCs) were analyzed during adipogenic differentiation in vitro. Here, we show that the capacity to differentiate from DPSCs or PLSCs to adipocytes may be associated with the expression pattern of DNA methylation-related genes acquired during the induction of the adipogenic program. Our study provides insights into the details of DNA methylation during the adipogenic determination of dental stem cells, which can be a starting point to identify the factors that affect the differentiation of these cells and provide new strategies to regulate differentiation and adipocyte expansion.
Collapse
Affiliation(s)
- Adaylu A. Argaez-Sosa
- Facultad de Ingeniería Química, Campus de Ciencias Exactas e Ingeniería, Universidad Autónoma de Yucatán, Mérida, Mexico
| | - Beatriz A. Rodas-Junco
- Laboratorio Translacional de Células Troncales, Facultad de Odontología, Universidad Autónoma de Yucatán, Mérida, Mexico
- CONACYT-Facultad de Ingeniería Química, Campus de Ciencias Exactas e Ingeniería, Universidad Autónoma de Yucatán, Mérida, Mexico
| | - Leydi M. Carrillo-Cocom
- Facultad de Ingeniería Química, Campus de Ciencias Exactas e Ingeniería, Universidad Autónoma de Yucatán, Mérida, Mexico
| | - Rafael A. Rojas-Herrera
- Facultad de Ingeniería Química, Campus de Ciencias Exactas e Ingeniería, Universidad Autónoma de Yucatán, Mérida, Mexico
| | - Abel Coral-Sosa
- Facultad de Ingeniería Química, Campus de Ciencias Exactas e Ingeniería, Universidad Autónoma de Yucatán, Mérida, Mexico
| | - Fernando J. Aguilar-Ayala
- Laboratorio Translacional de Células Troncales, Facultad de Odontología, Universidad Autónoma de Yucatán, Mérida, Mexico
| | - David Aguilar-Pérez
- Laboratorio Translacional de Células Troncales, Facultad de Odontología, Universidad Autónoma de Yucatán, Mérida, Mexico
| | - Geovanny I. Nic-Can
- Laboratorio Translacional de Células Troncales, Facultad de Odontología, Universidad Autónoma de Yucatán, Mérida, Mexico
- CONACYT-Facultad de Ingeniería Química, Campus de Ciencias Exactas e Ingeniería, Universidad Autónoma de Yucatán, Mérida, Mexico
- *Correspondence: Geovanny I. Nic-Can, ,
| |
Collapse
|
|
15
|
Dental Pulp Stem Cell Heterogeneity: Finding Superior Quality "Needles" in a Dental Pulpal "Haystack" for Regenerative Medicine-Based Applications. Stem Cells Int 2022; 2022:9127074. [PMID: 35027930 PMCID: PMC8752304 DOI: 10.1155/2022/9127074] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 11/03/2021] [Indexed: 12/14/2022] Open
Abstract
Human dental pulp stem/stromal cells (hDPSCs) derived from the permanent secondary dentition are recognised to possess certain advantageous traits, which support their potential use as a viable source of mesenchymal stem/stromal cells (MSCs) for regenerative medicine-based applications. However, the well-established heterogeneous nature of hDPSC subpopulations, coupled with their limited numbers within dental pulp tissues, has impeded our understanding of hDPSC biology and the translation of sufficient quantities of these cells from laboratory research, through successful therapy development and clinical applications. This article reviews our current understanding of hDPSC biology and the evidence underpinning the molecular basis of their heterogeneity, which may be exploited to distinguish individual subpopulations with specific or superior characteristics for regenerative medicine applications. Pertinent unanswered questions which still remain, regarding the developmental origins, hierarchical organisation, and stem cell niche locations of hDPSC subpopulations and their roles in hDPSC heterogeneity and functions, will further be explored. Ultimately, a greater understanding of how key features, such as specific cell surface, senescence and other relevant genes, and protein and metabolic markers, delineate between hDPSC subpopulations with contrasting stemness, proliferative, multipotency, immunomodulatory, anti-inflammatory, and other relevant properties is required. Such knowledge advancements will undoubtedly lead to the development of novel screening, isolation, and purification strategies, permitting the routine and effective identification, enrichment, and expansion of more desirable hDPSC subpopulations for regenerative medicine-based applications. Furthermore, such innovative measures could lead to improved cell expansion, manufacture, and banking procedures, thereby supporting the translational development of hDPSC-based therapies in the future.
Collapse
|
|
16
|
Kabakov L, Nemcovsky CE, Plasmanik-Chor M, Meir H, Bar DZ, Weinberg E. Fibroblasts from the oral masticatory and lining mucosa have different gene expression profiles and proliferation rates. J Clin Periodontol 2021; 48:1393-1401. [PMID: 34409631 DOI: 10.1111/jcpe.13532] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 08/02/2021] [Indexed: 12/13/2022]
Abstract
AIMS To compare the gene expression profiles and proliferation rates of fibroblasts from the oral lining and masticatory mucosae. MATERIALS AND METHODS Primary human fibroblasts were retrieved from the posterior masticatory hard palate and the lining alveolar mucosa of five individuals. The gene expression profile was evaluated using total RNA sequencing. The proliferation rate was determined colorimetrically. RESULTS Substantial differences in specific gene groups and pathways were observed between fibroblasts from the two tissues. Significantly enriched gene ontology processes were focused on the extracellular components. Lining mucosa fibroblasts exhibited significantly higher expression of the principal structural collagens, cranial neural crest markers, and homeobox genes associated with positional memory. Masticatory mucosa fibroblasts showed greater expression of genes related to transforming growth factor-β signalling, which may be associated with fibrosis. In addition, they expressed higher levels of the EP2 prostaglandin E2 receptor and Toll-like receptor 1. Finally, masticatory mucosa fibroblasts exhibited a 10%-30% higher proliferation rate. CONCLUSIONS Fibroblasts from the lining and masticatory oral mucosae are phenotypically heterogeneous, presenting distinct gene expression profiles and proliferation rates. These features may contribute to their specific physiological functions and have relevance for potential therapeutic applications.
Collapse
Affiliation(s)
- Liron Kabakov
- Department of Oral Biology, Goldschleger School of Dental Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
| | - Carlos E Nemcovsky
- Department of Periodontology and Oral Implantology, Goldschleger School of Dental Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Metsada Plasmanik-Chor
- Bioinformatics Unit, George S. Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, Israel
| | - Haya Meir
- Department of Periodontology and Oral Implantology, Goldschleger School of Dental Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Daniel Z Bar
- Department of Oral Biology, Goldschleger School of Dental Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
| | - Evgeny Weinberg
- Department of Oral Biology, Goldschleger School of Dental Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.,Department of Periodontology and Oral Implantology, Goldschleger School of Dental Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| |
Collapse
|
|
17
|
Khodabandeh Z, Haghighat S, Tanideh N, Zare S, Farrokhi F, Karandish M, Iraji A. Comparing the effects of Elaegnus Angustifolia, Hypericum Perforatum and Psidium Guajava extracts on metabolic activity of dental pulp-derived mesenchymal stem cells. Cell Tissue Bank 2021; 23:143-155. [PMID: 33843009 DOI: 10.1007/s10561-021-09923-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 03/30/2021] [Indexed: 02/07/2023]
Abstract
Dental pulp derived-mesenchymal stem cells (DP-MSCs) is considered a suitable are candidate for tissue engineering techniques and osseous reconstruction. Based on the hypothesis that Hypericum perforatum, Elaeagnus Angustifolia and Psidium guajava extracts can be used in cell-based bone tissue engineering due to meagre cytotoxicity response in the cell culture medium, their effects on the viability and metabolic activity of DP-MSCs were investigated and compared with each extract. DP-MSCs were extracted from human dental pulp, characterized by flow cytometry, and differentiated into Osteogenic and adipogenic lineages which were then cultured in different concentrations of E. Angustifolia, H. perforatum and P. guajava extracts at different time intervals followed by MTT assay evaluation. The dental pulp mesenchymal stem cells were evaluated for their plastic adherence ability, fibroblast-like and spindle morphology. According to flow cytometry data, isolated cells from DP-MSCs expressed MSCs markers. A comparison of herbal extracts' concentrations revealed that 500 μg/ml was toxic to dental pulp stem cells, a guide to the toxic dose for DP-MSCs. The P.guajava bore low toxicity and increased dental pulp stem cell viability in comparison to the other two herbal extracts. The hydro-alcoholic extracts of E. Angustifolia, H. perforatum, and P. guajava were efficient in DP-MSCs viability, and therefore were concluded to be useful in maintaining structural and functional cell viability. It was also concluded that the co-culture of stem cells with herbal elements could stimulate endogenous factors to enhance the proliferation and viability of MSCs.
Collapse
Affiliation(s)
- Zahra Khodabandeh
- Stem Cells Technology Research Center, Shiraz University of Medical Science, Shiraz, Iran
| | - Sara Haghighat
- School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nader Tanideh
- Stem Cells Technology Research Center, Shiraz University of Medical Science, Shiraz, Iran
- Pharmacology Department, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Shahrokh Zare
- Stem Cells Technology Research Center, Shiraz University of Medical Science, Shiraz, Iran
| | - Farnaz Farrokhi
- School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Karandish
- Orthodontic Department, Dental School, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Aida Iraji
- Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Central Research Laboratory, Shiraz University of Medical Sciences, Ghasrdasht St, Shiraz, Iran
| |
Collapse
|
|
18
|
Weber M, Wehrhan F, Deschner J, Sander J, Ries J, Möst T, Bozec A, Gölz L, Kesting M, Lutz R. The Special Developmental Biology of Craniofacial Tissues Enables the Understanding of Oral and Maxillofacial Physiology and Diseases. Int J Mol Sci 2021; 22:ijms22031315. [PMID: 33525669 PMCID: PMC7866214 DOI: 10.3390/ijms22031315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/21/2021] [Accepted: 01/25/2021] [Indexed: 11/21/2022] Open
Abstract
Maxillofacial hard tissues have several differences compared to bones of other localizations of the human body. These could be due to the different embryological development of the jaw bones compared to the extracranial skeleton. In particular, the immigration of neuroectodermally differentiated cells of the cranial neural crest (CNC) plays an important role. These cells differ from the mesenchymal structures of the extracranial skeleton. In the ontogenesis of the jaw bones, the development via the intermediate stage of the pharyngeal arches is another special developmental feature. The aim of this review was to illustrate how the development of maxillofacial hard tissues occurs via the cranial neural crest and pharyngeal arches, and what significance this could have for relevant pathologies in maxillofacial surgery, dentistry and orthodontic therapy. The pathogenesis of various growth anomalies and certain syndromes will also be discussed.
Collapse
Affiliation(s)
- Manuel Weber
- Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany; (F.W.); (J.R.); (T.M.); (M.K.); (R.L.)
- Correspondence: ; Tel.: +49-9131-854-3749
| | - Falk Wehrhan
- Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany; (F.W.); (J.R.); (T.M.); (M.K.); (R.L.)
- Private Office for Maxillofacial Surgery, 91781 Weißenburg, Germany
| | - James Deschner
- Department of Periodontology and Operative Dentistry, University of Mainz, 55131 Mainz, Germany;
| | - Janina Sander
- Private Office for Oral Surgery, 96049 Bamberg, Germany;
| | - Jutta Ries
- Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany; (F.W.); (J.R.); (T.M.); (M.K.); (R.L.)
| | - Tobias Möst
- Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany; (F.W.); (J.R.); (T.M.); (M.K.); (R.L.)
| | - Aline Bozec
- Department of Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany;
| | - Lina Gölz
- Department of Orthodontics, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany;
| | - Marco Kesting
- Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany; (F.W.); (J.R.); (T.M.); (M.K.); (R.L.)
| | - Rainer Lutz
- Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany; (F.W.); (J.R.); (T.M.); (M.K.); (R.L.)
| |
Collapse
|
|
19
|
Hosmani J, Assiri K, Almubarak HM, Mannakandath ML, Al-Hakami A, Patil S, Babji D, Sarode S, Devaraj A, Chandramoorthy HC. Proteomic profiling of various human dental stem cells - a systematic review. World J Stem Cells 2020; 12:1214-1236. [PMID: 33178402 PMCID: PMC7596439 DOI: 10.4252/wjsc.v12.i10.1214] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 08/06/2020] [Accepted: 09/01/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The proteomic signature or profile best describes the functional component of a cell during its routine metabolic and survival activities. Additional complexity in differentiation and maturation is observed in stem/progenitor cells. The role of functional proteins at the cellular level has long been attributed to anatomical niches, and stem cells do not deflect from this attribution. Human dental stem cells (hDSCs), on the whole, are a combination of mesenchymal and epithelial coordinates observed throughout craniofacial bones to pulp.
AIM To specify the proteomic profile and compare each type of hDSC with other mesenchymal stem cells (MSCs) of various niches. Furthermore, we analyzed the characteristics of the microenvironment and preconditioning changes associated with the proteomic profile of hDSCs and their influence on committed lineage differentiation.
METHODS Literature searches were performed in PubMed, EMBASE, Scopus, and Web of Science databases, from January 1990 to December 2018. An extra inquiry of the grey literature was completed on Google Scholar, ProQuest, and OpenGrey. Relevant MeSH terms (PubMed) and keywords related to dental stem cells were used independently and in combination.
RESULTS The initial search resulted in 134 articles. Of the 134 full-texts assessed, 96 articles were excluded and 38 articles that met the eligibility criteria were reviewed. The overall assessment of hDSCs and other MSCs suggests that differences in the proteomic profile can be due to stem cellular complexity acquired from varied tissue sources during embryonic development. However, our comparison of the proteomic profile suffered inconsistencies due to the heterogeneity of various hDSCs. We believe that the existence of a heterogeneous population of stem cells at a given niche determines the modalities of regeneration or tissue repair. Added prominences to the differences present between various hDSCs have been reasoned out.
CONCLUSION Systematic review on proteomic studies of various hDSCs are promising as an eye-opener for revisiting the proteomic profile and in-depth analysis to elucidate more refined mechanisms of hDSC functionalities.
Collapse
Affiliation(s)
- Jagadish Hosmani
- Diagnostic Dental Sciences, College of Dentistry, King Khalid University, Abha 61471, Asir, Saudi Arabia
| | - Khalil Assiri
- Diagnostic Dental Sciences, King Khalid University, Abha 61471, Asir, Saudi Arabia
| | | | | | - Ahmed Al-Hakami
- Center for Stem Cell Research and Department of Microbiology and Clinical Parasitology, King Khalid University, Abha 61421, Asir, Saudi Arabia
| | - Shankargouda Patil
- Maxillofacial Surgery and Diagnostic Sciences, Division of oral Pathology, Jazan 45142, Jazan, Saudi Arabia
| | - Deepa Babji
- Department of Oral Pathology and Microbiology, Maratha Mandal's NG Halgekar Institute of Dental Sciences and Research Centre, Belgaun 590 010, Karnataka, India
| | - Sachin Sarode
- Department of Oral Pathology, Y Patil Dental College and Hospital, Pune 411018, Maharashtra, India
| | - Anantharam Devaraj
- Center for Stem Cell Research and Department of Microbiology and Clinical Parasitology, King Khalid University, Abha 61421, Asir, Saudi Arabia
| | - Harish C Chandramoorthy
- Center for Stem Cell Research and Department of Microbiology and Clinical Parasitology, King Khalid University, Abha 61421, Asir, Saudi Arabia
| |
Collapse
|
|
20
|
Alfonso García SL, Parada-Sanchez MT, Arboleda Toro D. The phenotype of gingival fibroblasts and their potential use in advanced therapies. Eur J Cell Biol 2020; 99:151123. [PMID: 33070040 DOI: 10.1016/j.ejcb.2020.151123] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 08/13/2020] [Accepted: 08/15/2020] [Indexed: 02/06/2023] Open
Abstract
Advanced therapies in medicine use stem cells, gene editing, and tissues to treat a wide range of conditions. One of their goals is to stimulate endogenous repair of tissues and organs by manipulating stem cells and their niche, as well as to optimize the intrinsic characteristics and plasticity of differentiated cells in adult tissues. In this context, fibroblasts emerge as an alternative source to stem cells because they share phenotypic and regenerative characteristics. Specifically, fibroblasts of the oral mucosae have been shown to have improved regenerative capacity compared to other fibroblast populations. Additionally, their easy access by means of minimally invasive procedures without generating aesthetic problems, with easy and rapid in vitro expansion and with great capacity to respond to extrinsic factors, make oral fibroblasts an attractive and interesting resource for regenerative medicine. This review summarizes current concepts regarding the phenotypic and functional aspects of human Gingival Fibroblasts and their niche, differentiating them from other fibroblast populations of oral-lining mucosa and skin fibroblasts. Furthermore, some applications are presented in regenerative medicine, emphasizing on the biological potential of human Gingival Fibroblasts.
Collapse
Affiliation(s)
- Sandra Liliana Alfonso García
- Department of Integrated Basic Studies, Faculty of Dentistry, Universidad de Antioquia, Medellín, 050010, Colombia; Department of Oral Health, Faculty of Dentistry, Universidad Nacional de Colombia, Bogotá, 111311, Colombia.
| | | | - David Arboleda Toro
- Department of Integrated Basic Studies, Faculty of Dentistry, Universidad de Antioquia, Medellín, 050010, Colombia
| |
Collapse
|
|
21
|
Abuarqoub D, Aslam N, Almajali B, Shajrawi L, Jafar H, Awidi A. Neuro-regenerative potential of dental stem cells: a concise review. Cell Tissue Res 2020; 382:267-279. [PMID: 32725424 DOI: 10.1007/s00441-020-03255-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 07/06/2020] [Indexed: 10/23/2022]
Abstract
This review will summarize the research information regarding the regenerative potential of dental stem cells for the treatment of neurodegenerative disorders. As compared to existing treatment modalities, the stem cell therapy seems promising, and accumulating evidences about the differentiation of stem cells into various lineages are proving it. The incidence of neurodegenerative diseases such as Alzheimer's, Parkinson's, stroke, and peripheral neuropathy is increasing due to the rise in life expectancies of people which have put a huge burden on economies. Finding a promising treatment could benefit not only the patients but also the communities. Dental stem cells hold a great potential to differentiate into neuronal cells. Many studies have reported the differentiation potential of the dental stem cells with the presence of neuronal lineage markers. In this review, we conferred how the use of dental stem cells can benefit the above-mentioned bedridden diseases.
Collapse
Affiliation(s)
- Duaa Abuarqoub
- Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan. .,Cell Therapy Center, The University of Jordan, Amman, Jordan.
| | - Nazneen Aslam
- Cell Therapy Center, The University of Jordan, Amman, Jordan
| | - Bayan Almajali
- School of Medicine, The University of Jordan, Amman, Jordan
| | - Leen Shajrawi
- School of Medicine, The University of Jordan, Amman, Jordan
| | - Hanan Jafar
- Cell Therapy Center, The University of Jordan, Amman, Jordan.,School of Medicine, The University of Jordan, Amman, Jordan
| | - Abdalla Awidi
- Cell Therapy Center, The University of Jordan, Amman, Jordan. .,School of Medicine, The University of Jordan, Amman, Jordan.
| |
Collapse
|
|
22
|
Pagella P, Miran S, Neto E, Martin I, Lamghari M, Mitsiadis TA. Human dental pulp stem cells exhibit enhanced properties in comparison to human bone marrow stem cells on neurites outgrowth. FASEB J 2020; 34:5499-5511. [PMID: 32096581 DOI: 10.1096/fj.201902482r] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 01/22/2020] [Accepted: 02/12/2020] [Indexed: 12/17/2022]
Abstract
Mesenchymal stem cells (MSCs) have the capacity to self-renew and differentiate into specific cell types and are, therefore, key players during tissue repair and regeneration. The use of MSCs for the regeneration of tissues in vivo is increasingly being explored and already constitutes a promising alternative to existing clinical treatments. MSCs also exert paracrine and trophic functions, including the promotion of innervation that plays fundamental roles in regeneration and in restoration of the function of organs. Human bone marrow stem cells (hBMSCs) and human dental pulp stem cells (hDPSCs) have been used in studies that aimed at the repair and/or regeneration of bone or other tissues of the craniofacial complex. However, the capabilities of hBMSCs and hDPSCs to elicit the growth of specific axons in order to reestablish functional innervation of the healing tissues are not known. Here, we compared the neurotrophic effects of hDPSCs and hBMSCs on trigeminal and dorsal root ganglia neurons using microfluidic organs-on-chips devices. We found that hDPSCs express significantly higher levels of neurotrophins than hBMSCs and consequently neurons cocultured with hDPSCs develop longer axons in the microfluidic co-culture system when compared to neurons cocultured with hBMSCs. Moreover, hDPSCs elicited the formation of extensive axonal networks and established close contacts with neurons, a phenomenon not observed in presence of hBMSCs. Taken together, these findings indicate that hDPSCs constitute a superior option for restoring the functionality of damaged craniofacial tissues, as they are able to support and promote extensive trigeminal innervation.
Collapse
Affiliation(s)
- Pierfrancesco Pagella
- Orofacial Development and Regeneration, Institute of Oral Biology, Centre of Dental Medicine, University of Zurich, Zurich, Switzerland
| | - Shayee Miran
- Orofacial Development and Regeneration, Institute of Oral Biology, Centre of Dental Medicine, University of Zurich, Zurich, Switzerland
| | - Estrela Neto
- i3S, University of Porto, Porto, Portugal.,Institute of Biomedical Engineering (INEB), University of Porto, Porto, Portugal
| | - Ivan Martin
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Meriem Lamghari
- i3S, University of Porto, Porto, Portugal.,Institute of Biomedical Engineering (INEB), University of Porto, Porto, Portugal
| | - Thimios A Mitsiadis
- Orofacial Development and Regeneration, Institute of Oral Biology, Centre of Dental Medicine, University of Zurich, Zurich, Switzerland
| |
Collapse
|
|
23
|
Liu Y, Dong R, Zhang C, Yang Y, Xu Y, Wang H, Zhang M, Zhu J, Wang Y, Sun Y, Zhang Z. Therapeutic effects of nerve leachate-treated adipose-derived mesenchymal stem cells on rat sciatic nerve injury. Exp Ther Med 2019; 19:223-231. [PMID: 31853293 PMCID: PMC6909684 DOI: 10.3892/etm.2019.8203] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Accepted: 09/26/2019] [Indexed: 02/06/2023] Open
Abstract
Peripheral nerve injury (PNI) is a common condition, often resulting from physical nerve injury and trauma. Successful repair of the peripheral nerve is dependent on the regenerative activity of Schwann cells (SCs). Application of SC-like adipose-derived mesenchymal stem cells (ADSCs) may be a suitable cell-based therapy for PNI. In the present study, nerve leachate derived from the rat sciatic nerve was used to induce the differentiation of ADSCs. These cells were placed in an acellular biological scaffold, which was then grafted to a rat sciatic nerve to bridge a 1-cm gap. Sprague-Dawley rats were divided into four groups: Scaffold only, untreated ADSCs + scaffold, nerve leachate-treated ADSCs + scaffold and autograft. Two-months post-transplant, the structure and function of the regenerated nerves and the recovery of the innervated muscles was analyzed. After transplant, there was a significant increase in the average area (15.86%; P<0.05), density (23.13%; P<0.05) and thickness (43.24%; P<0.05) of regenerated nerve fibers in the nerve leachate-treated ADSCs + scaffold group compared with the untreated ADSCs + scaffold group. The nerve conduction velocity in the nerve leachate-treated ADSCs + scaffold and autograft groups was superior to that in the other groups. In the nerve leachate-treated ADSCs + scaffold group, the cross-sectional area of the gastrocnemius increased by 39.28% (P<0.05) and the cross-sectional area of collagen fibers decreased by 29.87% (P<0.05) compared with the ADSCs + scaffold group. Moreover, the therapeutic effect of nerve leachate-treated ADSCs + scaffold on PNI was similar to that of an autograft. These results suggest that nerve leachate-treated ADSCs may promote the repair of PNI.
Collapse
Affiliation(s)
- Yumei Liu
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471023, P.R. China
| | - Ruiqi Dong
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471023, P.R. China
| | - Chunyan Zhang
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471023, P.R. China
| | - Yuxiang Yang
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471023, P.R. China
| | - Yaolu Xu
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471023, P.R. China
| | - Haojie Wang
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471023, P.R. China
| | - Mengyu Zhang
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471023, P.R. China
| | - Jiamin Zhu
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471023, P.R. China
| | - Yuqin Wang
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471023, P.R. China.,Engineering Research Center for Mutton Sheep Breeding of Henan Province, Luoyang, Henan 471023, P.R. China
| | - Yanhong Sun
- Department of Physiology, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010110, P.R. China
| | - Ziqiang Zhang
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471023, P.R. China
| |
Collapse
|
|
24
|
Wnt Signaling in Neural Crest Ontogenesis and Oncogenesis. Cells 2019; 8:cells8101173. [PMID: 31569501 PMCID: PMC6829301 DOI: 10.3390/cells8101173] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 09/23/2019] [Accepted: 09/25/2019] [Indexed: 02/06/2023] Open
Abstract
Neural crest (NC) cells are a temporary population of multipotent stem cells that generate a diverse array of cell types, including craniofacial bone and cartilage, smooth muscle cells, melanocytes, and peripheral neurons and glia during embryonic development. Defective neural crest development can cause severe and common structural birth defects, such as craniofacial anomalies and congenital heart disease. In the early vertebrate embryos, NC cells emerge from the dorsal edge of the neural tube during neurulation and then migrate extensively throughout the anterior-posterior body axis to generate numerous derivatives. Wnt signaling plays essential roles in embryonic development and cancer. This review summarizes current understanding of Wnt signaling in NC cell induction, delamination, migration, multipotency, and fate determination, as well as in NC-derived cancers.
Collapse
|
|
25
|
Rasch A, Naujokat H, Wang F, Seekamp A, Fuchs S, Klüter T. Evaluation of bone allograft processing methods: Impact on decellularization efficacy, biocompatibility and mesenchymal stem cell functionality. PLoS One 2019; 14:e0218404. [PMID: 31220118 PMCID: PMC6586299 DOI: 10.1371/journal.pone.0218404] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 05/31/2019] [Indexed: 12/19/2022] Open
Abstract
In an ever-aging society the demand for bone-defect filling grafts continues to gain in importance. While autologous grafting still prevails as the gold standard, allografts and xenografts present viable alternatives with promising results. Physiochemical properties of a graft strongly depend on the processing method such as the decellularization protocol. In addition, the physiochemical characteristics are critical factors for a successful integration of the graft after the implantation and might influence mesenchymal stem cell function in therapeutic approaches combining grafts and autologous mesenchymal stem cells (MSCs). Several decellularization methods have been proposed, however it still remains unclear which method results in favorable physiochemical properties or might be preferred in stem cell applications. In the first part of this study we compared two decellularization approaches resulting in chemically processed allografts (CPAs) or sonication-based processed allografts (SPAs). Each decellularization approach was compared for its decellularization efficacy and its influence on the grafts' surface texture and composition. In the second part of this study biocompatibility of grafts was assessed by testing the effect of extraction medium on MSC viability and comparing them to commercially available allografts and xenografts. Additionally, grafts' performance in terms of MSC functionality was assessed by reseeding with MSCs pre-differentiated in osteogenic medium and determining cell adhesion, proliferation, as well as alkaline phosphatase (ALP) activity and the degree of mineralization. In summary, results indicate a more effective decellularization for the SPA approach in comparison to the CPA approach. Even though SPA extracts induced a decrease in MSC viability, MSC performance after reseeding was comparable to commercially available grafts based on DNA quantification, alkaline phosphatase activity and quantification of mineralization. Commercial Tutoplast allografts showed overall the best effects on MSC functionality as indicated by extraction biocompatibility testing as well as by comparing proliferation and osteogenic differentiation.
Collapse
Affiliation(s)
- Alexander Rasch
- Experimental Trauma Surgery, Department of Trauma and Orthopedic Surgery, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Hendrik Naujokat
- Experimental Trauma Surgery, Department of Trauma and Orthopedic Surgery, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
- Department of Oral and Maxillofacial Surgery, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Fanlu Wang
- Experimental Trauma Surgery, Department of Trauma and Orthopedic Surgery, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Andreas Seekamp
- Experimental Trauma Surgery, Department of Trauma and Orthopedic Surgery, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Sabine Fuchs
- Experimental Trauma Surgery, Department of Trauma and Orthopedic Surgery, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
- * E-mail:
| | - Tim Klüter
- Experimental Trauma Surgery, Department of Trauma and Orthopedic Surgery, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
| |
Collapse
|
|
26
|
Martín-de-Llano JJ, Mata M, Peydró S, Peydró A, Carda C. Dentin tubule orientation determines odontoblastic differentiation in vitro: A morphological study. PLoS One 2019; 14:e0215780. [PMID: 31071116 PMCID: PMC6508697 DOI: 10.1371/journal.pone.0215780] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 04/08/2019] [Indexed: 01/09/2023] Open
Abstract
Odontoblasts are post-mitotic cells responsible for maintenance of the dentin, and are therefore important for dental health. In some cases, irreversible pulpitis leads to necrosis and consequently death of odontoblasts. Regenerative endodontics (RE) uses the concept of tissue engineering to restore the root canals to a healthy state, allowing for continued development of the root and surrounding tissue. Human dental pulp stem cells (hDPSCs) have been successfully used in RE to restore odontoblast function. Surface microgeometry is one of the most important factors involved in the induction of differentiation of hDPSCs into odontoblast-like cells. Although different authors have demonstrated the importance of a dentin-like surface with accessible dentin tubules to induce differentiation of hDPSCs, the ultrastructural characteristics of the cells and the secreted extracellular matrix have not been studied in depth. Here, we used an acellular dentin scaffold containing dentin tubules in different spatial geometries, which regulated their accessibility to cells. hDPSCs were cultured on the scaffolds for up to 6 weeks. Systematic characterization of differentiated cells was performed using both optical (hematoxylin and eosin, Masson trichrome, and immunohistochemical determination of dentin sialoprotein [DSSP]) and transmission electron microscopy. The results presented here indicated that cells grown on the dentin surface containing accessible dentin tubules developed a characteristic odontoblastic phenotype, with cellular processes similar to native odontoblasts. The cell organization and characteristics of secreted extracellular matrix were also similar to those of native dentin tissue. Cells grown on non-accessible dentin tubule surfaces secreted a more abundant and dense extracellular matrix, and developed a different phenotype consisting of secretory flat cells organized in layers. Cells grown far from the scaffold, i.e., directly on the culture well surface, developed a secretory phenotype probably influenced by biochemical factors released by the dentin scaffold or differentiated cells. The results presented here support the use of hDPSCs to regenerate dentin and show the utility of scaffold microgeometry for determining the differentiation and secretory phenotype of cultured cells.
Collapse
Affiliation(s)
- José Javier Martín-de-Llano
- Department of Pathology. Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
- Fundación para la Investigación del Hospital Clínico de la Comunidad Valenciana (INCLIVA), Valencia, Spain
| | - Manuel Mata
- Department of Pathology. Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
- Fundación para la Investigación del Hospital Clínico de la Comunidad Valenciana (INCLIVA), Valencia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
- * E-mail:
| | - Santiago Peydró
- Department of Pathology. Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
| | - Amando Peydró
- Department of Pathology. Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
| | - Carmen Carda
- Department of Pathology. Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
- Fundación para la Investigación del Hospital Clínico de la Comunidad Valenciana (INCLIVA), Valencia, Spain
- Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBERBBN), Madrid, Spain
| |
Collapse
|
|
27
|
Collignon AM, Castillo-Dali G, Gomez E, Guilbert T, Lesieur J, Nicoletti A, Acuna-Mendoza S, Letourneur D, Chaussain C, Rochefort GY, Poliard A. Mouse Wnt1-CRE
-Rosa
Tomato
Dental Pulp Stem Cells Directly Contribute to the Calvarial Bone Regeneration Process. Stem Cells 2019; 37:701-711. [DOI: 10.1002/stem.2973] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 12/14/2018] [Accepted: 12/19/2018] [Indexed: 01/08/2023]
Affiliation(s)
- Anne-Margaux Collignon
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
- University Hospitals, AP-HP; Paris France
| | - Gabriel Castillo-Dali
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
| | - Eduardo Gomez
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
| | - Thomas Guilbert
- Plateforme IMAG'IC, Institut Cochin, Inserm U1016-CNRS UMR8104; University Paris Descartes; Paris France
| | - Julie Lesieur
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
| | - Antonino Nicoletti
- INSERM U1148, Laboratory of Vascular Translational Science; University Paris Diderot, University Paris 13, Bichat Hospital, and Département Hospitalo-Universitaire (DHU) FIRE; Paris France
| | - Soledad Acuna-Mendoza
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
| | - Didier Letourneur
- INSERM U1148, Laboratory of Vascular Translational Science; University Paris Diderot, University Paris 13, Bichat Hospital, and Département Hospitalo-Universitaire (DHU) FIRE; Paris France
| | - Catherine Chaussain
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
- University Hospitals, AP-HP; Paris France
| | - Gael Y. Rochefort
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
| | - Anne Poliard
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
| |
Collapse
|
|
28
|
Proteasomal inhibition attenuates craniofacial malformations in a zebrafish model of Treacher Collins Syndrome. Biochem Pharmacol 2019; 163:362-370. [PMID: 30849304 DOI: 10.1016/j.bcp.2019.03.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 03/04/2019] [Indexed: 01/07/2023]
Abstract
Treacher Collins Syndrome (TCS) is a congenital disease characterized by defects in the craniofacial skeleton and absence of mental alterations. Recently we modelled TCS in zebrafish (Danio rerio) embryos through the microinjection of Morpholino® oligonucleotides blocking the translation of the ortholog of the main causative gene (TCOF1). We showed that Cnbp, a key cytoprotective protein involved in normal rostral head development, was detected in lower levels (without changes in its mRNA expression) in TCS-like embryos. As previous reports suggested that Cnbp is degraded through the proteasomal pathway, we tested whether proteasome inhibitors (MG132 and Bortezomib (Velcade®, Millennium laboratories)) were able to ameliorate cranial skeleton malformations in TCS. Here we show that treatment with both proteasome inhibitors produced a robust craniofacial cartilage phenotype recovery. This recovery seems to be consequence of a decreased degradation of Cnbp in TCS-like embryos. Critical TCS manifestations, such as neuroepithelial cell death and cell redox imbalance were attenuated. Thus, proteasome inhibitors may offer an opportunity for TCS molecular and phenotypic manifestation's prevention. Although further development of new safe inhibitors compatible with administration during pregnancy is required, our results encourage this therapeutic approach.
Collapse
|
|
29
|
Salehi MS, Borhani-Haghighi A, Pandamooz S, Safari A, Dargahi L, Dianatpour M, Tanideh N. Dimethyl fumarate up-regulates expression of major neurotrophic factors in the epidermal neural crest stem cells. Tissue Cell 2019; 56:114-120. [PMID: 30736899 DOI: 10.1016/j.tice.2019.01.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 01/20/2019] [Accepted: 01/21/2019] [Indexed: 02/07/2023]
Abstract
There is an agreement that combining treatments can lead to substantial improvement, therefore the present study assessed the effects of different concentrations of dimethyl fumarate (DMF) on viability of epidermal neural crest stem cells (EPI-NCSCs). In addition, this investigation was designed to evaluate the effects of DMF on relative expression of major trophic factors mainly the ones with neurotrophic effects, expressed in EPI-NCSCs in order to enhance their therapeutic potential. To determine the appropriate concentration of DMF for EPI-NCSCs treatment, the MTT assay was employed and based on the obtained data, EPI-NCSCs treated with 10μM DMF for 6, 24, 72 or 168 h. In each time point, quantitative RT-PCR technique was used to evaluate NGF, NT-3, BDNF, GDNF and VEGF transcripts. The acquired data showed that 10μM DMF significantly increased the mRNA expression of NGF, NT-3 and BDNF, 72 h following treatment; however, DMF inhibitory effect on GDNF mRNA expression was observed in various time points. No significant changes were detected for VEGF transcript. Our findings reveled that expression of major neurotrophic factors were up-regulated by dimethyl fumarate treatment. Therefore, combining EPI-NCSCs with DMF treatment might be a valuable strategy to improve their therapeutic functions in vivo.
Collapse
Affiliation(s)
- Mohammad Saied Salehi
- Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Sareh Pandamooz
- Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Anahid Safari
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Leila Dargahi
- Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Dianatpour
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nader Tanideh
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| |
Collapse
|
|
30
|
Aquino-Martínez R, Monroe DG, Ventura F. Calcium mimics the chemotactic effect of conditioned media and is an effective inducer of bone regeneration. PLoS One 2019; 14:e0210301. [PMID: 30608979 PMCID: PMC6319750 DOI: 10.1371/journal.pone.0210301] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Accepted: 12/18/2018] [Indexed: 12/22/2022] Open
Abstract
Background After bone resorption, ions and degraded organic components are co-released into the extracellular space. Ions and growth factors, although different in their biological nature, induce a common and coordinated chemotactic effect. Conditioned media has been used successfully in bone regeneration by promoting endogenous cell recruitment. Likewise, calcium alone act as a paracrine chemotactic signal, inducing the host’s undifferentiated progenitor cell infiltration into the implanted biomaterials. The aim of the present study was to compare the chemotactic effect of calcium and conditioned media in primary calvarial cells. Methods The chemotactic cell response was evaluated in vitro using an agarose spot and a wound healing assay. In addition, we used a calvarial bone explant model ex-vivo. The healing potential was also tested through an in vivo model, a critical-size calvarial bone defect in mice. For the in vivo experiment, cell-free calcium-containing or conditioned media-containing scaffolds were implanted, and MSC’s seeded scaffolds were used as positive control. After seven weeks post-implantation, samples were retrieved, and bone regeneration was evaluated by μCT and histological analysis. Osteogenic gene expression was evaluated by qPCR. Results We found that chemotactic cell migration in response to either calcium or conditioned media was equivalent in vitro and ex vivo. Accordingly, μCT analysis showed that bone regeneration induced by the MSC’s seeded scaffolds was similar to that obtained with cell-free calcium or conditioned media-containing scaffolds. Pre-treatment with SB202190, a highly selective p38 inhibitor, abrogated the chemotactic effect induced by conditioned media. In contrast, p38 activity was not essential for the calcium-induced chemotaxis. Moreover, BAPTA-AM treatment, a cytosolic calcium chelator, decreased the chemotactic effect and the expression of key osteogenic genes induced by calcium or conditioned media. Conclusion We show that calcium ions alone not only mimic the conditioned media chemotactic effect, but also induce an osteogenic effect similar to that produced by transplanted MSC’s in vivo. Furthermore, the chemotactic effect induced by conditioned media is calcium and p38 dependent. The rise in cytosolic calcium might integrate the different signaling pathways triggered by conditioned media and extracellular Ca2+. This calcium-driven in situ bone regeneration is a promising and convenient alternative to promote endogenous cell recruitment into the injured bone site. This pre-clinical cell-free and growth factor-free approach might avoid the disadvantages of the ex vivo cell manipulation.
Collapse
Affiliation(s)
- Rubén Aquino-Martínez
- Departament de Ciències Fisiològiques, Universitat de Barcelona, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain
- Department of Medicine, Division of Endocrinology, Mayo Clinic College of Medicine, Rochester, MN, United States of America
| | - David G. Monroe
- Department of Medicine, Division of Endocrinology, Mayo Clinic College of Medicine, Rochester, MN, United States of America
| | - Francesc Ventura
- Departament de Ciències Fisiològiques, Universitat de Barcelona, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain
- * E-mail:
| |
Collapse
|
|
31
|
Petridis X, Beems BP, Tomson PL, Scheven B, Giepmans BNG, Kuipers J, van der Sluis LWM, Harmsen MC. Effect of Dentin Matrix Components on the Mineralization of Human Mesenchymal Stromal Cells. Tissue Eng Part A 2018; 25:1104-1115. [PMID: 30444193 DOI: 10.1089/ten.tea.2018.0192] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
IMPACT STATEMENT This research has been conducted with the aim to contribute to the development of treatment modalities for the reconstruction of lost/damaged mineralized tissues. Currently, determining the most appropriate stromal cell population and signaling cues stands at the core of developing effective treatments. We provide new insights into the effect of innate inductive cues found in human dentin matrix components, on the osteogenic differentiation of various human stromal cell types. The effects of dentin extracellular matrix components on umbilical cord mesenchymal stromal cells have not been investigated before. The findings of this study could underpin translational research based on the development of techniques for mineralized tissue engineering and will be of great interest for the readership of Tissue Engineering Part A.
Collapse
Affiliation(s)
- Xenos Petridis
- 1Center for Dentistry and Oral Hygiene, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Bas P Beems
- 1Center for Dentistry and Oral Hygiene, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Phillip L Tomson
- 2School of Dentistry, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Ben Scheven
- 2School of Dentistry, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Ben N G Giepmans
- 3Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Jeroen Kuipers
- 3Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Luc W M van der Sluis
- 1Center for Dentistry and Oral Hygiene, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Martin C Harmsen
- 4Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| |
Collapse
|
|
32
|
Tsuruta T, Sakai K, Watanabe J, Katagiri W, Hibi H. Dental pulp-derived stem cell conditioned medium to regenerate peripheral nerves in a novel animal model of dysphagia. PLoS One 2018; 13:e0208938. [PMID: 30533035 PMCID: PMC6289419 DOI: 10.1371/journal.pone.0208938] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Accepted: 11/26/2018] [Indexed: 12/27/2022] Open
Abstract
In nerve regeneration studies, various animal models are used to assess nerve regeneration. However, because of the difficulties in functional nerve assessment, a visceral nerve injury model is yet to be established. The superior laryngeal nerve (SLN) plays an essential role in swallowing. Although a treatment for SLN injury following trauma and surgery is desirable, no such treatment is reported in the literature. We recently reported that stem cells derived from human exfoliated deciduous teeth (SHED) have a therapeutic effect on various tissues via macrophage polarization. Here, we established a novel animal model of SLN injury. Our model was characterized as having weight loss and drinking behavior changes. In addition, the SLN lesion caused a delay in the onset of the swallowing reflex and gain of laryngeal residue in the pharynx. Systemic administration of SHED-conditioned media (SHED-CM) promoted functional recovery of the SLN and significantly promoted axonal regeneration by converting of macrophages to the anti-inflammatory M2 phenotype. In addition, SHED-CM enhanced new blood vessel formation at the injury site. Our data suggest that the administration of SHED-CM may provide therapeutic benefits for SLN injury.
Collapse
Affiliation(s)
- Takeshi Tsuruta
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kiyoshi Sakai
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
- * E-mail:
| | - Junna Watanabe
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Wataru Katagiri
- Division of Reconstructive Surgery for Oral and Maxillofacial Region, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Hideharu Hibi
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| |
Collapse
|
|
33
|
Zhang Y, Kato H, Sato H, Yamaza H, Hirofuji Y, Han X, Masuda K, Nonaka K. Folic acid-mediated mitochondrial activation for protection against oxidative stress in human dental pulp stem cells derived from deciduous teeth. Biochem Biophys Res Commun 2018; 508:850-856. [PMID: 30528238 DOI: 10.1016/j.bbrc.2018.11.169] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 11/27/2018] [Indexed: 12/18/2022]
Abstract
Enzymatic antioxidant systems, mainly involving mitochondria, are critical for minimizing the harmful effects of reactive oxygen species, and these systems are enhanced by interactions with nonenzymatic antioxidant nutrients. Because fetal growth requires extensive mitochondrial respiration, pregnant women and fetuses are at high risk of exposure to excessive reactive oxygen species. The enhancement of the antioxidant system, e.g., by nutritional management, is therefore critical for both the mother and fetus. Folic acid supplementation prevents homocysteine accumulation and epigenetic dysregulation associated with one-carbon metabolism. However, few studies have examined the antioxidant effects of folic acid for healthy pregnancy outcomes. The purpose of this study was to elucidate the association between the antioxidant effect of folic acid and mitochondria in undifferentiated cells during fetal growth. Neural crest-derived dental pulp stem cells of human exfoliated deciduous teeth were used as a model of undifferentiated cells in the fetus. Pyocyanin induced excessive reactive oxygen species, resulting in a decrease in cell growth and migration accompanied by mitochondrial fragmentation and inactivation in dental pulp stem cells. This damage was significantly improved by folic acid, along with decreased mitochondrial reactive oxygen species, PGC-1α upregulation, DRP1 downregulation, mitochondrial elongation, and increased ATP production. Folic acid may protect undifferentiated cells from oxidative damage by targeting mitochondrial activation. These results provide evidence for a new benefit of folic acid in pregnant women and fetuses.
Collapse
Affiliation(s)
- Yu Zhang
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Hiroki Kato
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
| | - Hiroshi Sato
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Haruyoshi Yamaza
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Yuta Hirofuji
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Xu Han
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Keiji Masuda
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
| | - Kazuaki Nonaka
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| |
Collapse
|
|
34
|
MicroRNA 210 Mediates VEGF Upregulation in Human Periodontal Ligament Stem Cells Cultured on 3DHydroxyapatite Ceramic Scaffold. Int J Mol Sci 2018; 19:ijms19123916. [PMID: 30563289 PMCID: PMC6320762 DOI: 10.3390/ijms19123916] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Revised: 12/03/2018] [Accepted: 12/05/2018] [Indexed: 12/19/2022] Open
Abstract
The aim of the present research was the evaluation of the behavior of human periodontal ligament stem cells (hPDLSCs), cultured in presence of Endobon® Xenograft Granules (G), a fully deproteinated hydroxyapatite ceramic scaffold derived from cancellous bovine bone. hPDLSCs were seeded with and without G for 24 h to 1 week. The cell growth, morphological features, adhesiveness, differentiation ability, modulation of miR-210 and Vascular Endothelial Growth Factor (VEGF) secretion were analyzed by means of MTT assay, Scanning Electron Microscopy (SEM), Confocal Laser Scanning Microscopy (CLSM), Alizarin Red S assay, RT-PCR and ELISA test, respectively. hPDLSCs grown on the biomaterial showed the ability to form focal adhesion on the substrate, as demonstrated by vinculin expression. These data were supported by SEM analysis showing that an adhesiveness process associated to cell growth occurs between cells and biomaterials. The osteogenic differentiation, evaluated by morphological, biochemical, and RT-PCR analysis, was pronounced in the hPDLSCs grown in the three-dimensional inorganic bovine bone substitute in the presence of osteoinductive conditions. In addition, an upregulation of miR-210 and VEGF was evident in cells cultured in presence of the biomaterial. Our results inspire us to consider granules not only an adequate biocompatible three-dimensional biomaterial, but also an effective inductor of miR-210 and VEGF; in fact, the involvement of miR-210 in VEGF secretion could offer a novel regulatory system in the early steps of the bone-regeneration process.
Collapse
|
|
35
|
Orciani M, Caffarini M, Torresetti M, Campanati A, Parodi P, Di Benedetto G, Di Primio R. Breast Implant Texturization Does Not Affect the Crosstalk Between MSC and ALCL Cells. Inflammation 2018; 42:721-730. [PMID: 30446982 DOI: 10.1007/s10753-018-0930-4] [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: 11/30/2022]
Abstract
In the last decade, there has been a growing interest about the possible association between anaplastic large cell lymphoma (ALCL) and breast implants (BIA-ALCL). Many variables, such as breast implants texturization, have been investigated. Breast implants often lead to the formation of a periprosthetic capsule, characterized by inflammation. The presence of the inflamed capsule has been found in the majority of patients with BIA-ALCL. Inflammation may be sustained or counteracted by mesenchymal stem cells (MSCs) by the secretion of pro- or anti-inflammatory cytokines. MSCs were isolated from three capsules surrounding micro-textured (micro-MSCs) and from three capsules surrounding macro-textured (macro-MSCs) implants; after characterization, MSCs were co-cultured with KI-JK cells (a cell line derived from the cutaneous form of ALCL). The secretion of cytokines related to inflammation, the proliferation rate, and the expression of genes referred to pro-tumoral mechanisms were evaluated. Co-cultures of KI-JK cells with micro- or macro-MSCs gave the same results about the secretion of cytokines (increase of IL10, G-CSF, and TGF-β1 and decrease of IL4, IL5, IL12, IL13, IL17A, IFN-γ (p < 0.05) with respect to mock sample), expression of selected genes (increase for ACVR1, VEGF, TGF-βR2, CXCL12, and MKi67 (p < 0.05) with respect to control sample), and the proliferation rate (no variation between mock and co-cultured samples). Our results suggest that MSCs derived from capsules surrounding micro- and macro-textured implants display the same effects on the ALCL cells.
Collapse
Affiliation(s)
- Monia Orciani
- Department of Clinical and Molecular Sciences- Histology, Università Politecnica delle Marche, Via Tronto 10/A, 60126, Ancona, Italy.
| | - Miriam Caffarini
- Department of Clinical and Molecular Sciences- Histology, Università Politecnica delle Marche, Via Tronto 10/A, 60126, Ancona, Italy
| | - Matteo Torresetti
- Department of Experimental and Clinical Medicine - Clinic of Plastic and Reconstructive Surgery, Università Politecnica delle Marche, Ancona, Italy
| | - Anna Campanati
- Department of Clinical and Molecular Sciences- Clinic of Dermatology, Università Politecnica delle Marche, Ancona, Italy
| | - Piercamillo Parodi
- Clinic of Plastic and Reconstructive Surgery of Udine, University of Udine, Udine, Italy
| | - Giovanni Di Benedetto
- Department of Experimental and Clinical Medicine - Clinic of Plastic and Reconstructive Surgery, Università Politecnica delle Marche, Ancona, Italy
| | - Roberto Di Primio
- Department of Clinical and Molecular Sciences- Histology, Università Politecnica delle Marche, Via Tronto 10/A, 60126, Ancona, Italy
| |
Collapse
|
|
36
|
Iezzi I, Cerqueni G, Licini C, Lucarini G, Mattioli Belmonte M. Dental pulp stem cells senescence and regenerative potential relationship. J Cell Physiol 2018; 234:7186-7197. [PMID: 30362542 DOI: 10.1002/jcp.27472] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 08/30/2018] [Indexed: 12/30/2022]
Abstract
Uncomplicated treatments for pulpitis and periodontitis continues to be challenging and regenerative approaches could meet this contingency. Dental pulp stem cells (DPSCs) represent a good candidate for oral recovering therapies. Here, we investigated changes in morphology, proliferation, and in vitro differentiation toward mesenchymal and neuronal phenotypes of human DPSCs harvested from differently aged donors. Aging is a physiologic phenomenon occurring with time that hamper body's capability to maintain homeostasis also affecting the functional reserve. Cytofluorimetric, immunohistochemical, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and western blot analyses were performed to gain insight for successful regenerative strategies in elderly. We observed a decline in DPSCs proliferation and differentiation potential with age. Interestingly, these cells behaved differently under osteogenic or odontogenic stimuli, showing different age-related mineralization capabilities. Similarly, neurogenic differentiation decreased with age. In conclusion, our observations represent a valid tool for the development of tailored regenerative strategies in an aging society.
Collapse
Affiliation(s)
- Iolanda Iezzi
- Department of Clinical and Molecular Sciences-DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
| | - Giorgia Cerqueni
- Department of Clinical and Molecular Sciences-DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
| | - Caterina Licini
- Department of Clinical and Molecular Sciences-DISCLIMO, Università Politecnica delle Marche, Ancona, Italy.,Department of Applied Science and Technology (DISAT), Polytechnic of Turin, Turin, Italy
| | - Guendalina Lucarini
- Department of Clinical and Molecular Sciences-DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
| | - Monica Mattioli Belmonte
- Department of Clinical and Molecular Sciences-DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
| |
Collapse
|
|
37
|
Huang CC, Narayanan R, Warshawsky N, Ravindran S. Dual ECM Biomimetic Scaffolds for Dental Pulp Regenerative Applications. Front Physiol 2018; 9:495. [PMID: 29887803 PMCID: PMC5981804 DOI: 10.3389/fphys.2018.00495] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 04/18/2018] [Indexed: 12/16/2022] Open
Abstract
Dental pulp is a highly vascularized and innervated tissue that provides sensitivity and vitality to the tooth. Chronic caries results in an infected pulp tissue prone to necrosis. Existing clinical treatments replace the living pulp tissue with a non-responsive resin filling resulting in loss of tooth vitality. Tissue engineering approaches to dental pulp tissue regeneration have been investigated to preserve tooth vitality and function. However, a critical criterion is the choice of growth factors that may promote mesenchymal stem cell differentiation and more importantly, vascularization. But, the problems associated with growth factor dosage, delivery, safety, immunological and ectopic complications affect their translatory potential severely. The purpose of this study is to develop, characterize and evaluate a biomimetic native extracellular matrix (ECM) derived dual ECM scaffold that consists of a pulp-specific ECM to promote MSC attachment, proliferation and differentiation and an endothelial ECM to promote migration of host endothelial cells and eventual vascularization in vivo. Our results show that the dual ECM scaffolds possess similar properties as a pulp-ECM scaffold to promote MSC attachment and odontogenic differentiation in vitro. Additionally, when implanted subcutaneously in a tooth root slice model in vivo, the dual ECM scaffolds promoted robust odontogenic differentiation of both dental pulp and bone marrow derived MSCs and also extensive vascularization when compared to respective controls. These scaffolds are mass producible for clinical use and hence have the potential to replace root canal therapy as a treatment for chronic dental caries.
Collapse
Affiliation(s)
- Chun-Chieh Huang
- Department of Oral Biology, University of Illinois at Chicago, Chicago, IL, United States.,Department of Endodontics, University of Illinois at Chicago, Chicago, IL, United States
| | - Raghuvaran Narayanan
- Department of Oral Biology, University of Illinois at Chicago, Chicago, IL, United States.,Department of Endodontics, University of Illinois at Chicago, Chicago, IL, United States
| | - Noah Warshawsky
- Department of Oral Biology, University of Illinois at Chicago, Chicago, IL, United States.,Department of Endodontics, University of Illinois at Chicago, Chicago, IL, United States
| | - Sriram Ravindran
- Department of Oral Biology, University of Illinois at Chicago, Chicago, IL, United States.,Department of Endodontics, University of Illinois at Chicago, Chicago, IL, United States
| |
Collapse
|
|
38
|
Marei MK, El Backly RM. Dental Mesenchymal Stem Cell-Based Translational Regenerative Dentistry: From Artificial to Biological Replacement. Front Bioeng Biotechnol 2018; 6:49. [PMID: 29770323 PMCID: PMC5941981 DOI: 10.3389/fbioe.2018.00049] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 04/11/2018] [Indexed: 12/13/2022] Open
Abstract
Dentistry is a continuously changing field that has witnessed much advancement in the past century. Prosthodontics is that branch of dentistry that deals with replacing missing teeth using either fixed or removable appliances in an attempt to simulate natural tooth function. Although such "replacement therapies" appear to be easy and economic they fall short of ever coming close to their natural counterparts. Complications that arise often lead to failures and frequent repairs of such devices which seldom allow true physiological function of dental and oral-maxillofacial tissues. Such factors can critically affect the quality of life of an individual. The market for dental implants is continuously growing with huge economic revenues. Unfortunately, such treatments are again associated with frequent problems such as peri-implantitis resulting in an eventual loss or replacement of implants. This is particularly influential for patients having co-morbid diseases such as diabetes or osteoporosis and in association with smoking and other conditions that undoubtedly affect the final treatment outcome. The advent of tissue engineering and regenerative medicine therapies along with the enormous strides taken in their associated interdisciplinary fields such as stem cell therapy, biomaterial development, and others may open arenas to enhancing tissue regeneration via designing and construction of patient-specific biological and/or biomimetic substitutes. This review will overview current strategies in regenerative dentistry while overviewing key roles of dental mesenchymal stem cells particularly those of the dental pulp, until paving the way to precision/translational regenerative medicine therapies for future clinical use.
Collapse
Affiliation(s)
- Mona K Marei
- Department of Removable Prosthodontics, Faculty of Dentistry, Alexandria University, Alexandria, Egypt.,Tissue Engineering Laboratories, Faculty of Dentistry, Alexandria University, Alexandria, Egypt
| | - Rania M El Backly
- Tissue Engineering Laboratories, Faculty of Dentistry, Alexandria University, Alexandria, Egypt.,Endodontics, Conservative Dentistry Department, Faculty of Dentistry, Alexandria University, Alexandria, Egypt
| |
Collapse
|
|
39
|
3D bio-printed scaffold-free nerve constructs with human gingiva-derived mesenchymal stem cells promote rat facial nerve regeneration. Sci Rep 2018; 8:6634. [PMID: 29700345 PMCID: PMC5919929 DOI: 10.1038/s41598-018-24888-w] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Accepted: 04/11/2018] [Indexed: 02/06/2023] Open
Abstract
Despite the promising neuro-regenerative capacities of stem cells, there is currently no licensed stem cell-based product in the repair and regeneration of peripheral nerve injuries. Here, we explored the potential use of human gingiva-derived mesenchymal stem cells (GMSCs) as the only cellular component in 3D bio-printed scaffold-free neural constructs that were transplantable to bridge facial nerve defects in rats. We showed that GMSCs have the propensity to aggregate into compact 3D-spheroids that could produce their own matrix. When cultured under either 2D- or 3D-collagen scaffolds, GMSC spheroids were found to be more capable of differentiating into both neuronal and Schwann-like cells than their adherent counterparts. Using a scaffold-free 3D bio-printer system, nerve constructs were printed from GMSC spheroids in the absence of exogenous scaffolds and allowed to mature in a bioreactor. In vivo transplantation of the GMSC-laden nerve constructs promoted regeneration and functional recovery when used to bridge segmental defects in rat facial nerves. Our findings suggest that GMSCs represent an easily accessible source of MSCs for 3D bio-printing of scaffold-free nervous tissue constructs with promising potential application for repair and regeneration of peripheral nerve defects.
Collapse
|
|
40
|
Intrastriatal transplantation of stem cells from human exfoliated deciduous teeth reduces motor defects in Parkinsonian rats. Cytotherapy 2018; 20:670-686. [PMID: 29576501 DOI: 10.1016/j.jcyt.2018.02.371] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Revised: 02/11/2018] [Accepted: 02/21/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND This study explored the neural differentiation and therapeutic effects of stem cells from human exfoliated deciduous teeth (SHED) in a rat model of Parkinson's disease (PD). METHODS The SHED were isolated from fresh dental pulp and were induced to differentiate to neurons and dopamine neurons by inhibiting similar mothers against dpp (SMAD) signaling with Noggin and increase conversion of dopamine neurons from SHED with CHIR99021, Sonic Hedgehog (SHH) and FGF8 in vitro. The neural-primed SHED were transplanted to the striatum of 6-hydroxydopamine (6-OHDA)-induced PD rats to evaluate their neural differentiation and functions in vivo. RESULTS These SHED were efficiently differentiated to neurons (62.7%) and dopamine neurons (42.3%) through a newly developed method. After transplantation, the neural-induced SHED significantly improved recovery of the motor deficits of the PD rats. The grafted SHED were differentiated into neurons (61%), including dopamine neurons (22.3%), and integrated into the host rat brain by forming synaptic connections. Patch clamp analysis showed that neurons derived from grafted SHED have the same membrane potential profile as dopamine neurons, indicating these cells are dopamine neuron-like cells. The potential molecular mechanism of SHED transplantation in alleviating motor deficits of the rats is likely to be mediated by neuronal replacement and immune-modulation as we detected the transplanted dopamine neurons and released immune cytokines from SHED. CONCLUSION Using neural-primed SHED to treat PD showed significant restorations of motor deficits in 6-OHDA-induced rats. These observations provide further evidence that SHED can be used for cell-based therapy of PD.
Collapse
|
|
41
|
Zhang Q, Nguyen PD, Shi S, Burrell JC, Xu Q, Cullen KD, Le AD. Neural Crest Stem-Like Cells Non-genetically Induced from Human Gingiva-Derived Mesenchymal Stem Cells Promote Facial Nerve Regeneration in Rats. Mol Neurobiol 2018; 55:6965-6983. [PMID: 29372546 DOI: 10.1007/s12035-018-0913-3] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Accepted: 01/15/2018] [Indexed: 02/07/2023]
Abstract
Non-genetic induction of somatic cells into neural crest stem-like cells (NCSCs) is promising for potential cell-based therapies for post-traumatic peripheral nerve regeneration. Here, we report that human gingiva-derived mesenchymal stem cells (GMSCs) could be reproducibly and readily induced into NCSCs via non-genetic approaches. Compared to parental GMSCs, induced NCSC population had increased expression in NCSC-related genes and displayed robust differentiation into neuronal and Schwann-like cells. Knockdown of the expression of Yes-associated protein 1 (YAP1), a critical mechanosensor and mechanotransducer, attenuated the expression of NCSC-related genes; specific blocking of RhoA/ROCK activity and non-muscle myosin II (NM II)-dependent contraction suppressed YAP1 and NCSC-related genes and concurrently abolished neural spheroid formation in NCSCs. Using a rat model of facial nerve defect, implantation of NCSC-laden nerve conduits promoted functional regeneration of the injured nerve. These promising findings demonstrate that induced NCSCs derived from GMSCs represent an easily accessible and promising source of neural stem-like cells for peripheral nerve regeneration.
Collapse
Affiliation(s)
- Qunzhou Zhang
- Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine, 240 South 40th Street, Philadelphia, PA, 19104, USA
| | - Phuong D Nguyen
- Division of Plastic and Reconstructive Surgery, University of Pennsylvania Perelman School of Medicine, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA
| | - Shihong Shi
- Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine, 240 South 40th Street, Philadelphia, PA, 19104, USA
| | - Justin C Burrell
- Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, 3320 Smith Walk, Philadelphia, PA, 19104, USA
| | - Qilin Xu
- Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine, 240 South 40th Street, Philadelphia, PA, 19104, USA
| | - Kacy D Cullen
- Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, 3320 Smith Walk, Philadelphia, PA, 19104, USA
| | - Anh D Le
- Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine, 240 South 40th Street, Philadelphia, PA, 19104, USA.
- Department of Oral and Maxillofacial Surgery, Penn Medicine Hospital of the University of Pennsylvania, Perelman Center for Advanced Medicine, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA.
| |
Collapse
|
|
42
|
A High-Resolution Proteomic Landscaping of Primary Human Dental Stem Cells: Identification of SHED- and PDLSC-Specific Biomarkers. Int J Mol Sci 2018; 19:ijms19010158. [PMID: 29304003 PMCID: PMC5796107 DOI: 10.3390/ijms19010158] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 12/25/2017] [Accepted: 12/29/2017] [Indexed: 02/06/2023] Open
Abstract
Dental stem cells (DSCs) have emerged as a promising tool for basic research and clinical practice. A variety of adult stem cell (ASC) populations can be isolated from different areas within the dental tissue, which, due to their cellular and molecular characteristics, could give rise to different outcomes when used in potential applications. In this study, we performed a high-throughput molecular comparison of two primary human adult dental stem cell (hADSC) sub-populations: Stem Cells from Human Exfoliated Deciduous Teeth (SHEDs) and Periodontal Ligament Stem Cells (PDLSCs). A detailed proteomic mapping of SHEDs and PDLSCs, via employment of nano-LC tandem-mass spectrometry (MS/MS) revealed 2032 identified proteins in SHEDs and 3235 in PDLSCs. In total, 1516 proteins were expressed in both populations, while 517 were unique for SHEDs and 1721 were exclusively expressed in PDLSCs. Further analysis of the recorded proteins suggested that SHEDs predominantly expressed molecules that are involved in organizing the cytoskeletal network, cellular migration and adhesion, whereas PDLSCs are highly energy-producing cells, vastly expressing proteins that are implicated in various aspects of cell metabolism and proliferation. Applying the Rho-GDI signaling pathway as a paradigm, we propose potential biomarkers for SHEDs and for PDLSCs, reflecting their unique features, properties and engaged molecular pathways.
Collapse
|
|
43
|
Rodas-Junco BA, Canul-Chan M, Rojas-Herrera RA, De-la-Peña C, Nic-Can GI. Stem Cells from Dental Pulp: What Epigenetics Can Do with Your Tooth. Front Physiol 2017; 8:999. [PMID: 29270128 PMCID: PMC5724083 DOI: 10.3389/fphys.2017.00999] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 11/20/2017] [Indexed: 12/16/2022] Open
Abstract
Adult stem cells have attracted scientific attention because they are able to self-renew and differentiate into several specialized cell types. In this context, human dental tissue-derived mesenchymal stem cells (hDT-MSCs) have emerged as a possible solution for repairing or regenerating damaged tissues. These cells can be isolated from primary teeth that are naturally replaced, third molars, or other dental tissues and exhibit self-renewal, a high proliferative rate and a great multilineage potential. However, the cellular and molecular mechanisms that determine lineage specification are still largely unknown. It is known that a change in cell fate requires the deletion of existing transcriptional programs, followed by the establishment of a new developmental program to give rise to a new cell lineage. Increasing evidence indicates that chromatin structure conformation can influence cell fate. In this way, reversible chemical modifications at the DNA or histone level, and combinations thereof can activate or inactivate cell-type-specific gene sequences, giving rise to an alternative cell fates. On the other hand, miRNAs are starting to emerge as a possible player in establishing particular somatic lineages. In this review, we discuss two new and promising research fields in medicine and biology, epigenetics and stem cells, by summarizing the properties of hDT-MSCs and highlighting the recent findings on epigenetic contributions to the regulation of cellular differentiation.
Collapse
Affiliation(s)
- Beatriz A Rodas-Junco
- CONACYT-Facultad de Ingeniería Química, Campus de Ciencias Exactas e Ingeniería, Universidad Autónoma de Yucatán, Mérida, Mexico
| | - Michel Canul-Chan
- Facultad de Ingeniería Química, Campus de Ciencias Exactas e Ingeniería, Universidad Autónoma de Yucatán, Mérida, Mexico
| | - Rafael A Rojas-Herrera
- Facultad de Ingeniería Química, Campus de Ciencias Exactas e Ingeniería, Universidad Autónoma de Yucatán, Mérida, Mexico
| | - Clelia De-la-Peña
- Unidad de Biotecnología, Centro de Investigación Científica de Yucatán, Mérida, Mexico
| | - Geovanny I Nic-Can
- CONACYT-Facultad de Ingeniería Química, Campus de Ciencias Exactas e Ingeniería, Universidad Autónoma de Yucatán, Mérida, Mexico
| |
Collapse
|
|
44
|
Prabha RD, Kraft DCE, Harkness L, Melsen B, Varma H, Nair PD, Kjems J, Kassem M. Bioactive nano‐fibrous scaffold for vascularized craniofacial bone regeneration. J Tissue Eng Regen Med 2017; 12:e1537-e1548. [DOI: 10.1002/term.2579] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2016] [Revised: 08/05/2017] [Accepted: 09/23/2017] [Indexed: 01/08/2023]
Affiliation(s)
- Rahul Damodaran Prabha
- Department of Endocrinology and MetabolismUniversity Hospital of Odense Odense Denmark
- Interdisciplinary Nanoscience Center (iNANO)Aarhus University Aarhus Denmark
- Section of Orthodontics, Department of DentistryAarhus University Aarhus Denmark
| | | | - Linda Harkness
- Department of Endocrinology and MetabolismUniversity Hospital of Odense Odense Denmark
| | - Birte Melsen
- Section of Orthodontics, Department of DentistryAarhus University Aarhus Denmark
| | - Harikrishna Varma
- Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST) Thiruvananthapuram Kerala India
| | - Prabha D. Nair
- Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST) Thiruvananthapuram Kerala India
| | - Jorgen Kjems
- Interdisciplinary Nanoscience Center (iNANO)Aarhus University Aarhus Denmark
| | - Moustapha Kassem
- Department of Endocrinology and MetabolismUniversity Hospital of Odense Odense Denmark
| |
Collapse
|
|
45
|
Human Dental Pulp Cells Differentiate toward Neuronal Cells and Promote Neuroregeneration in Adult Organotypic Hippocampal Slices In Vitro. Int J Mol Sci 2017; 18:ijms18081745. [PMID: 28800076 PMCID: PMC5578135 DOI: 10.3390/ijms18081745] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 08/08/2017] [Accepted: 08/08/2017] [Indexed: 12/11/2022] Open
Abstract
The adult mammalian central nerve system has fundamental difficulties regarding effective neuroregeneration. The aim of this study is to investigate whether human dental pulp cells (DPCs) can promote neuroregeneration by (i) being differentiated toward neuronal cells and/or (ii) stimulating local neurogenesis in the adult hippocampus. Using immunostaining, we demonstrated that adult human dental pulp contains multipotent DPCs, including STRO-1, CD146 and P75-positive stem cells. DPC-formed spheroids were able to differentiate into neuronal, vascular, osteogenic and cartilaginous lineages under osteogenic induction. However, under neuronal inductive conditions, cells in the DPC-formed spheroids differentiated toward neuronal rather than other lineages. Electrophysiological study showed that these cells consistently exhibit the capacity to produce action potentials, suggesting that they have a functional feature in neuronal cells. We further co-cultivated DPCs with adult mouse hippocampal slices on matrigel in vitro. Immunostaining and presto blue assay showed that DPCs were able to stimulate the growth of neuronal cells (especially neurons) in both the CA1 zone and the edges of the hippocampal slices. Brain-derived neurotrophic factor (BDNF), was expressed in co-cultivated DPCs. In conclusion, our data demonstrated that DPCs are well-suited to differentiate into the neuronal lineage. They are able to stimulate neurogenesis in the adult mouse hippocampus through neurotrophic support in vitro.
Collapse
|
|
46
|
Mortada I, Mortada R, Al Bazzal M. Dental pulp stem cells and the management of neurological diseases: An update. J Neurosci Res 2017; 96:265-272. [PMID: 28736906 DOI: 10.1002/jnr.24122] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 07/05/2017] [Accepted: 07/05/2017] [Indexed: 01/08/2023]
Abstract
Medical research in regenerative medicine has brought promising perspectives for the use of stem cells in clinical trials. Stem cells are undifferentiated cells capable of multilineage differentiation and available in numerous sources in the human body. Dental pulp constitutes an attractive source of these cells since collecting mesenchymal stem cells from this site is a noninvasive practice that can be performed after a common surgical extraction of supernumerary or wisdom teeth. Thus, tissue sacrifice is very low and several cytotypes can be obtained owing to these cells' multipotency, in addition to the fact that they can be cryopreserved and stored for long periods. Mesenchymal stem cells have high proliferation rates, making them favorable for clinical application. These multipotent cells, present in biological waste, constitute an appropriate resource in the treatment of many neurological diseases.
Collapse
Affiliation(s)
- Ibrahim Mortada
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Rola Mortada
- Lebanese University School of Dentistry, Beirut, Lebanon
| | | |
Collapse
|
|
47
|
Chen CC, Hsia CW, Ho CW, Liang CM, Chen CM, Huang KL, Kang BH, Chen YH. Hypoxia and hyperoxia differentially control proliferation of rat neural crest stem cells via distinct regulatory pathways of the HIF1α-CXCR4 and TP53-TPM1 proteins. Dev Dyn 2017; 246:162-185. [PMID: 28002632 DOI: 10.1002/dvdy.24481] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 12/09/2016] [Accepted: 12/13/2016] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Neural crest stem cells (NCSCs) are a population of adult multipotent stem cells. We are interested in studying whether oxygen tensions affect the capability of NCSCs to self-renew and repair damaged tissues. NCSCs extracted from the hair follicle bulge region of the rat whisker pad were cultured in vitro under different oxygen tensions. RESULTS We found significantly increased and decreased rates of cell proliferation in rat NCSCs (rNCSCs) cultured, respectively, at 0.5% and 80% oxygen levels. At 0.5% oxygen, the expression of both hypoxia-inducible factor (HIF) 1α and CXCR4 was greatly enhanced in the rNCSC nuclei and was suppressed by incubation with the CXCR4-specific antagonist AMD3100. In addition, the rate of cell apoptosis in the rNCSCs cultured at 80% oxygen was dramatically increased, associated with increased nuclear expression of TP53, decreased cytoplasmic expression of TPM1 (tropomyosin-1), and increased nuclear-to-cytoplasmic translocation of S100A2. Incubation of rNCSCs with the antioxidant N-acetylcysteine (NAC) overcame the inhibitory effect of 80% oxygen on proliferation and survival of rNCSCs. CONCLUSIONS Our results show for the first time that extreme oxygen tensions directly control NCSC proliferation differentially via distinct regulatory pathways of proteins, with hypoxia via the HIF1α-CXCR4 pathway and hyperoxia via the TP53-TPM1 pathway. Developmental Dynamics 246:162-185, 2017. © 2016 Wiley Periodicals, Inc.
Collapse
Affiliation(s)
- Chien-Cheng Chen
- Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Neihu District, Taipei City, Taiwan
| | - Ching-Wu Hsia
- Department of Finance, School of Management, Shih Hsin University, Wenshan District, Taipei City, Taiwan
| | - Cheng-Wen Ho
- Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Neihu District, Taipei City, Taiwan
- Division of Rehabilitation Medicine, Taoyuan Armed Forces General Hospital, Longtan District, Taoyuan City, Taiwan
| | - Chang-Min Liang
- Department of Ophthalmology, Tri-Service General Hospital, Neihu District, Taipei City, Taiwan
| | - Chieh-Min Chen
- Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Neihu District, Taipei City, Taiwan
| | - Kun-Lun Huang
- Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Neihu District, Taipei City, Taiwan
- Department of Undersea and Hyperbaric Medicine, Tri-Service General Hospital, Neihu District, Taipei City, Taiwan
| | - Bor-Hwang Kang
- Division of Diving Medicine, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Zuoying District, Kaohsiung City, Taiwan
- Department of Otorhinolaryngology - Head and Neck Surgery, Tri-Service General Hospital, Taipei City, Taiwan
| | - Yi-Hui Chen
- Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Neihu District, Taipei City, Taiwan
| |
Collapse
|
|
48
|
Gazarian KG, Ramírez-García LR. Human Deciduous Teeth Stem Cells (SHED) Display Neural Crest Signature Characters. PLoS One 2017; 12:e0170321. [PMID: 28125654 PMCID: PMC5268458 DOI: 10.1371/journal.pone.0170321] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 01/03/2017] [Indexed: 01/09/2023] Open
Abstract
Human dental tissues are sources of neural crest origin multipotent stem cells whose regenerative potential is a focus of extensive studies. Rational programming of clinical applications requires a more detailed knowledge of the characters inherited from neural crest. Investigation of neural crest cells generated from human pluripotent stem cells provided opportunity for their comparison with the postnatal dental cells. The purpose of this study was to investigate the role of the culture conditions in the expression by dental cells of neural crest characters. The results of the study demonstrate that specific neural crest cells requirements, serum-free, active WNT signaling and inactive SMAD 2/3, are needed for the activity of the neural crest characters in dental cells. Specifically, the decreasing concentration of fetal bovine serum (FBS) from regularly used for dental cells 10% to 2% and below, or using serum-free medium, led to emergence of a subset of epithelial-like cells expressing the two key neural crest markers, p75 and HNK-1. Further, the serum-free medium supplemented with neural crest signaling requirements (WNT inducer BIO and TGF-β inhibitor REPSOX), induced epithelial-like phenotype, upregulated the p75, Sox10 and E-Cadherin and downregulated the mesenchymal genes (SNAIL1, ZEB1, TWIST). An expansion medium containing 2% FBS allowed to obtain an epithelial/mesenchymal SHED population showing high proliferation, clonogenic, multi-lineage differentiation capacities. Future experiments will be required to determine the effects of these features on regenerative potential of this novel SHED population.
Collapse
Affiliation(s)
- Karlen G. Gazarian
- Department of Medicine Genomics and Environmental Toxicity, Institute of Biomedical Research, Mexican National Autonomous University, Mexico City, University Campus, Mexico
- * E-mail:
| | - Luis R. Ramírez-García
- Department of Medicine Genomics and Environmental Toxicity, Institute of Biomedical Research, Mexican National Autonomous University, Mexico City, University Campus, Mexico
| |
Collapse
|
|
49
|
Chalisserry EP, Nam SY, Park SH, Anil S. Therapeutic potential of dental stem cells. J Tissue Eng 2017; 8:2041731417702531. [PMID: 28616151 PMCID: PMC5461911 DOI: 10.1177/2041731417702531] [Citation(s) in RCA: 123] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 03/12/2017] [Indexed: 12/13/2022] Open
Abstract
Stem cell biology has become an important field in regenerative medicine and tissue engineering therapy since the discovery and characterization of mesenchymal stem cells. Stem cell populations have also been isolated from human dental tissues, including dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla, dental follicle progenitor cells, and periodontal ligament stem cells. Dental stem cells are relatively easily obtainable and exhibit high plasticity and multipotential capabilities. The dental stem cells represent a gold standard for neural-crest-derived bone reconstruction in humans and can be used for the repair of body defects in low-risk autologous therapeutic strategies. The bioengineering technologies developed for tooth regeneration will make substantial contributions to understand the developmental process and will encourage future organ replacement by regenerative therapies in a wide variety of organs such as the liver, kidney, and heart. The concept of developing tooth banking and preservation of dental stem cells is promising. Further research in the area has the potential to herald a new dawn in effective treatment of notoriously difficult diseases which could prove highly beneficial to mankind in the long run.
Collapse
Affiliation(s)
- Elna Paul Chalisserry
- Interdisciplinary Program of Marine-Bio, Electrical & Mechanical Engineering, Pukyong National University, Busan, Korea
- Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, Korea
| | - Seung Yun Nam
- Interdisciplinary Program of Marine-Bio, Electrical & Mechanical Engineering, Pukyong National University, Busan, Korea
- Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, Korea
- Department of Biomedical Engineering, Pukyong National University, Busan, South Korea
| | - Sang Hyug Park
- Interdisciplinary Program of Marine-Bio, Electrical & Mechanical Engineering, Pukyong National University, Busan, Korea
- Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, Korea
- Department of Biomedical Engineering, Pukyong National University, Busan, South Korea
| | - Sukumaran Anil
- Division of Periodontics, Department of Preventive Dental Sciences, College of Dentistry Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
| |
Collapse
|
|
50
|
Dental Pulp Stem Cells and Neurogenesis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 1083:63-75. [DOI: 10.1007/5584_2017_71] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
|