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1
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Satani N, Parsha K, Savitz SI. Enhancing Stroke Recovery With Cellular Therapies. Stroke 2022. [DOI: 10.1016/b978-0-323-69424-7.00062-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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2
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Huang L, Zheng Z, Bai D, Han X. Stem Cells from Human Exfoliated Deciduous Teeth and their Promise as Preventive and Therapeutic Strategies for Neurological Diseases and Injuries. Curr Stem Cell Res Ther 2021; 17:527-536. [PMID: 34967291 DOI: 10.2174/1574888x17666211229155533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 10/04/2021] [Accepted: 11/15/2021] [Indexed: 11/22/2022]
Abstract
Stem cells from human exfoliated deciduous teeth (SHEDs) are relatively easy to isolate from exfoliated deciduous teeth, which are obtained via dental therapy as biological waste. SHEDs originate from the embryonic neural crest and therefore have considerable potential for neurogenic differentiation. Currently, an increasing amount of research attention is focused on the therapeutic applications of SHEDs in neurological diseases and injuries. In this article, we summarize the biological characteristics of SHEDs and the potential role of SHEDs and their derivatives, including conditioned medium from SHEDs and the exosomes they secrete, in the prevention and treatment of neurological diseases and injuries.
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Affiliation(s)
- Lingyi Huang
- West China College of Stomatology/ State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China
| | - Zizhuo Zheng
- West China College of Stomatology/ State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China
| | - Ding Bai
- West China College of Stomatology/ State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China
| | - Xianglong Han
- West China College of Stomatology/ State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China
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3
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Duan R, Gao Y, He R, Jing L, Li Y, Gong Z, Yao Y, Luan T, Zhang C, Li L, Jia Y. Induced Pluripotent Stem Cells for Ischemic Stroke Treatment. Front Neurosci 2021; 15:628663. [PMID: 34135724 PMCID: PMC8202685 DOI: 10.3389/fnins.2021.628663] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 05/06/2021] [Indexed: 12/17/2022] Open
Abstract
Ischemic stroke is one of the main central nervous system diseases and is associated with high disability and mortality rates. Recombinant tissue plasminogen activator (rt-PA) and mechanical thrombectomy are the optimal therapies available currently to restore blood flow in patients with stroke; however, their limitations are well recognized. Therefore, new treatments are urgently required to overcome these shortcomings. Recently, stem cell transplantation technology, involving the transplantation of induced pluripotent stem cells (iPSCs), has drawn the interest of neuroscientists and is considered to be a promising alternative for ischemic stroke treatment. iPSCs are a class of cells produced by introducing specific transcription factors into somatic cells, and are similar to embryonic stem cells in biological function. Here, we have reviewed the current applications of stem cells with a focus on iPSC therapy in ischemic stroke, including the neuroprotective mechanisms, development constraints, major challenges to overcome, and clinical prospects. Based on the current state of research, we believe that stem cells, especially iPSCs, will pave the way for future stroke treatment.
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Affiliation(s)
- Ranran Duan
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yang Gao
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ruya He
- The International Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Lijun Jing
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yanfei Li
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhe Gong
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yaobing Yao
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Tingting Luan
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Chaopeng Zhang
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Li Li
- Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yanjie Jia
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Mukhamedshina Y, Shulman I, Ogurcov S, Kostennikov A, Zakirova E, Akhmetzyanova E, Rogozhin A, Masgutova G, James V, Masgutov R, Lavrov I, Rizvanov A. Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models. Biomolecules 2019; 9:E811. [PMID: 31805639 PMCID: PMC6995633 DOI: 10.3390/biom9120811] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 11/05/2019] [Accepted: 11/26/2019] [Indexed: 12/19/2022] Open
Abstract
Here, we provide a first comparative study of the therapeutic potential of allogeneic mesenchymal stem cells derived from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and dental pulp (DP-MSCs) embedded in fibrin matrix, in small (rat) and large (pig) spinal cord injury (SCI) models during subacute period of spinal contusion. Results of behavioral, electrophysiological, and histological assessment as well as immunohistochemistry and real-time polymerase chain reaction analysis suggest that application of AD-MSCs combined with a fibrin matrix within the subacute period in rats (2 weeks after injury), provides significantly higher post-traumatic regeneration compared to a similar application of BM-MSCs or DP-MSCs. Within the rat model, use of AD-MSCs resulted in a marked change in: (1) restoration of locomotor activity and conduction along spinal axons; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of microglial and astroglial activation. The effect of an autologous application of AD-MSCs during the subacute period after spinal contusion was also confirmed in pigs (6 weeks after injury). Effects included: (1) partial restoration of the somatosensory spinal pathways; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of astroglial activation in dorsal root entry zone. However, pigs only partially replicated the findings observed in rats. Together, these results indicate application of AD-MSCs embedded in fibrin matrix at the site of SCI during the subacute period can facilitate regeneration of nervous tissue in rats and pigs. These results, for the first time, provide robust support for the use of AD-MSC to treat subacute SCI.
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Affiliation(s)
- Yana Mukhamedshina
- Clinical Research Center for Precision and Regenerative Medicine, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; (I.S.); (S.O.); (A.K.); (E.Z.); (E.A.); (A.R.); (G.M.); (R.M.); (I.L.); (A.R.)
- Department of Histology, Cytology, and Embryology, Kazan State Medical University, 420012 Kazan, Russia
| | - Iliya Shulman
- Clinical Research Center for Precision and Regenerative Medicine, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; (I.S.); (S.O.); (A.K.); (E.Z.); (E.A.); (A.R.); (G.M.); (R.M.); (I.L.); (A.R.)
- Republic Clinical Hospital, 420138 Kazan, Russia
| | - Sergei Ogurcov
- Clinical Research Center for Precision and Regenerative Medicine, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; (I.S.); (S.O.); (A.K.); (E.Z.); (E.A.); (A.R.); (G.M.); (R.M.); (I.L.); (A.R.)
- Republic Clinical Hospital, 420138 Kazan, Russia
| | - Alexander Kostennikov
- Clinical Research Center for Precision and Regenerative Medicine, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; (I.S.); (S.O.); (A.K.); (E.Z.); (E.A.); (A.R.); (G.M.); (R.M.); (I.L.); (A.R.)
| | - Elena Zakirova
- Clinical Research Center for Precision and Regenerative Medicine, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; (I.S.); (S.O.); (A.K.); (E.Z.); (E.A.); (A.R.); (G.M.); (R.M.); (I.L.); (A.R.)
| | - Elvira Akhmetzyanova
- Clinical Research Center for Precision and Regenerative Medicine, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; (I.S.); (S.O.); (A.K.); (E.Z.); (E.A.); (A.R.); (G.M.); (R.M.); (I.L.); (A.R.)
| | - Alexander Rogozhin
- Clinical Research Center for Precision and Regenerative Medicine, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; (I.S.); (S.O.); (A.K.); (E.Z.); (E.A.); (A.R.); (G.M.); (R.M.); (I.L.); (A.R.)
- Department of Neurology, Kazan State Medical Academy–Branch Campus of the Federal State Budgetary Edicational Institution of Father Professional Education «Russian Medical Academy of Continuous Professional Education», 420012 Kazan, Russia
| | - Galina Masgutova
- Clinical Research Center for Precision and Regenerative Medicine, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; (I.S.); (S.O.); (A.K.); (E.Z.); (E.A.); (A.R.); (G.M.); (R.M.); (I.L.); (A.R.)
| | - Victoria James
- Division of Biomedical Science, School of Veterinary Medicine and Science, Faculty of Medicine and Health Sciences, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK;
| | - Ruslan Masgutov
- Clinical Research Center for Precision and Regenerative Medicine, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; (I.S.); (S.O.); (A.K.); (E.Z.); (E.A.); (A.R.); (G.M.); (R.M.); (I.L.); (A.R.)
- Republic Clinical Hospital, 420138 Kazan, Russia
| | - Igor Lavrov
- Clinical Research Center for Precision and Regenerative Medicine, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; (I.S.); (S.O.); (A.K.); (E.Z.); (E.A.); (A.R.); (G.M.); (R.M.); (I.L.); (A.R.)
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA
| | - Albert Rizvanov
- Clinical Research Center for Precision and Regenerative Medicine, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; (I.S.); (S.O.); (A.K.); (E.Z.); (E.A.); (A.R.); (G.M.); (R.M.); (I.L.); (A.R.)
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Qiao W, Lu L, Wu G, An X, Li D, Guo J. DPSCs seeded in acellular nerve grafts processed by Myroilysin improve nerve regeneration. J Biomater Appl 2018; 33:819-833. [PMID: 30449254 DOI: 10.1177/0885328218812136] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Since synthetic nerve conduits do not exhibit ideal regeneration characteristics, they are generally inadequate substitutes for autologous nerve grafts in the repair of long peripheral nerve defects. To resolve this problem, in this study, a nerve regeneration acellular nerve graft (ANG) with homologous dental pulp stem cells (DPSCs) was constructed. Xenogeneic ANG was processed by Myroilysin to completely remove cells and myelin sheath, while preserving extracellular matrix (ECM) microstructure of the natural nerve. The study revealed that ANG could support cell attachment and proliferation and did not stimulate a vigorous host rejection response. After inoculation of rabbit DPSCs (r-DPSCs) onto ANG, cells were observed to align along the longitudinal axis of the acellular nerve matrix (ANM) and persistently express NGF and BDNF. Undifferentiated r-DPSCs also presented glial cell characteristics and promoted nerve regeneration after transplantation in vivo. We repaired 1 cm purebred New Zealand White Rabbits sciatic nerve defects using this nerve graft construction, and nerve gap regeneration was indicated by electrophysiological and histological analysis. Therefore, we conclude that the combination of an ANG processed by Myroilysin with DPSCs providing a microenvironment that increases nerve regeneration for repairing peripheral nerve defects.
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Affiliation(s)
- Wenlan Qiao
- Department of Orthodontics, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, PR China
- Department of Stomatology, Qilu Hospital, and Institute of Stomatology, Shandong University, Jinan, PR China
| | - Lu Lu
- Department of Orthodontics, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, PR China
| | - Guangxue Wu
- Department of Orthodontics, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, PR China
| | - Xianglian An
- Department of Stomatology, Qilu Hospital, and Institute of Stomatology, Shandong University, Jinan, PR China
| | - Dong Li
- Department of Cryomedicine Lab, Qilu Hospital of Shandong University, Jinan, PR China
| | - Jing Guo
- Department of Orthodontics, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, PR China
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Raza SS, Wagner AP, Hussain YS, Khan MA. Mechanisms underlying dental-derived stem cell-mediated neurorestoration in neurodegenerative disorders. Stem Cell Res Ther 2018; 9:245. [PMID: 30257724 PMCID: PMC6158826 DOI: 10.1186/s13287-018-1005-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Neurodegenerative disorders have a complex pathology and are characterized by a progressive loss of neuronal architecture in the brain or spinal cord. Neuroprotective agents have demonstrated promising results at the preclinical stage, but this has not been confirmed at the clinical stage. Thus far, no neuroprotective drug that can prevent neuronal degeneration in patients with neurodegenerative disorders is available. MAIN BODY Recent studies have focused on neurorestorative measures, such as cell-based therapy, rather than neuroprotective treatment. The utility of cell-based approaches for the treatment of neurodegenerative disorders has been explored extensively, and the results have been somewhat promising with regard to reversing the outcome. Because of their neural crest origin, ease of harvest, accessibility, ethical suitability, and potential to differentiate into the neurogenic lineage, dental-derived stem cells (DSCs) have become an attractive source for cell-based neurorestoration therapies. In the present review, we summarize the possible use of DSC-based neurorestoration therapy as an alternative treatment for neurodegenerative disorders, with a particular emphasis on the mechanism underlying recovery in neurodegenerative disorders. CONCLUSION Transplantation research in neurodegenerative diseases should aim to understand the mechanism providing benefits both at the molecular and functional level. Due to their ease of accessibility, plasticity, and ethical suitability, DSCs hold promise to overcome the existing challenges in the field of neurodegeneration through multiple mechanisms, such as cell replacement, bystander effect, vasculogenesis, synaptogenesis, immunomodulation, and by inhibiting apoptosis.
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Affiliation(s)
- Syed Shadab Raza
- Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era Medical College & Hospital, Era University, Lucknow, Uttar Pradesh, 226003, India. .,Department of Stem Cell Biology and Regenerative Medicine, Era University, Lucknow, 226003, India.
| | - Aurel Popa Wagner
- Departmentof Dental Materials, RUHS College of Dental Sciences, Subhash Nagar, Jaipur, Rajasthan, 302002, India.,Center of Clinical and Experimental Medicine, University of Medicine and Pharmacy Craiova, Craiova, Romania.,School of Medicine, Griffith University, Southport, QLD, Australia
| | - Yawer S Hussain
- Department of Neurology, Chair of Vascular Neurology and Dementia, Essen University Hospital, Essen, Germany
| | - Mohsin Ali Khan
- Era Medical College & Hospital, Era University, Lucknow, Uttar Pradesh, 226003, India
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Sanches EF, Valentim L, de Almeida Sassi F, Bernardi L, Arteni N, Weis SN, Odorcyk FK, Pranke P, Netto CA. Intracardiac Injection of Dental Pulp Stem Cells After Neonatal Hypoxia-Ischemia Prevents Cognitive Deficits in Rats. Neurochem Res 2018; 43:2268-2276. [PMID: 30255215 DOI: 10.1007/s11064-018-2647-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Revised: 09/05/2018] [Accepted: 09/19/2018] [Indexed: 12/22/2022]
Abstract
Neonatal hypoxia-ischemia (HI) is associated to cognitive and motor impairments and until the moment there is no proven treatment. The underlying neuroprotective mechanisms of stem cells are partially understood and include decrease in excitotoxicity, apoptosis and inflammation suppression. This study was conducted in order to test the effects of intracardiac transplantation of human dental pulp stem cells (hDPSCs) for treating HI damage. Seven-day-old Wistar rats were divided into four groups: sham-saline, sham-hDPSCs, HI-saline, and HI-hDPSCs. Motor and cognitive tasks were performed from postnatal day 30. HI-induced cognitive deficits in the novel-object recognition test and in spatial reference memory impairment which were prevented by hDPSCs. No motor impairments were observed in HI animals. Immunofluorescence analysis showed human-positive nuclei in hDPSC-treated animals closely associated with anti-GFAP staining in the lesion scar tissue, suggesting that these cells were able to migrate to the injury site and could be providing support to CNS cells. Our study evidence novel evidence that hDPSC can contribute to the recovery following hypoxia-ischemia and highlight the need of further investigation in order to better understand the exact mechanisms underlying its neuroprotective effects.
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Affiliation(s)
- Eduardo Farias Sanches
- Brain Ischemia and Neuroprotection Laboratory, Departament of Biochemistry, Universidade Federal do Rio Grande do Sul, Av. Ramiro Barcelos, 2600, Porto Alegre, RS, CEP 91035-003, Brazil.
| | - Lauren Valentim
- Haematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.,Brain Ischemia and Neuroprotection Laboratory, Departament of Biochemistry, Universidade Federal do Rio Grande do Sul, Av. Ramiro Barcelos, 2600, Porto Alegre, RS, CEP 91035-003, Brazil
| | - Felipe de Almeida Sassi
- Haematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.,Brain Ischemia and Neuroprotection Laboratory, Departament of Biochemistry, Universidade Federal do Rio Grande do Sul, Av. Ramiro Barcelos, 2600, Porto Alegre, RS, CEP 91035-003, Brazil
| | - Lisiane Bernardi
- Haematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Nice Arteni
- Brain Ischemia and Neuroprotection Laboratory, Departament of Biochemistry, Universidade Federal do Rio Grande do Sul, Av. Ramiro Barcelos, 2600, Porto Alegre, RS, CEP 91035-003, Brazil
| | - Simone Nardin Weis
- Brain Ischemia and Neuroprotection Laboratory, Departament of Biochemistry, Universidade Federal do Rio Grande do Sul, Av. Ramiro Barcelos, 2600, Porto Alegre, RS, CEP 91035-003, Brazil
| | - Felipe Kawa Odorcyk
- Brain Ischemia and Neuroprotection Laboratory, Departament of Biochemistry, Universidade Federal do Rio Grande do Sul, Av. Ramiro Barcelos, 2600, Porto Alegre, RS, CEP 91035-003, Brazil
| | - Patricia Pranke
- Haematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.,Stem Cell Research Institute, Porto Alegre, Brazil
| | - Carlos Alexandre Netto
- Brain Ischemia and Neuroprotection Laboratory, Departament of Biochemistry, Universidade Federal do Rio Grande do Sul, Av. Ramiro Barcelos, 2600, Porto Alegre, RS, CEP 91035-003, Brazil
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Huang H, Young W, Chen L, Feng S, Zoubi ZMA, Sharma HS, Saberi H, Moviglia GA, He X, Muresanu DF, Sharma A, Otom A, Andrews RJ, Al-Zoubi A, Bryukhovetskiy AS, Chernykh ER, Domańska-Janik K, Jafar E, Johnson WE, Li Y, Li D, Luan Z, Mao G, Shetty AK, Siniscalco D, Skaper S, Sun T, Wang Y, Wiklund L, Xue Q, You SW, Zheng Z, Dimitrijevic MR, Masri WSE, Sanberg PR, Xu Q, Luan G, Chopp M, Cho KS, Zhou XF, Wu P, Liu K, Mobasheri H, Ohtori S, Tanaka H, Han F, Feng Y, Zhang S, Lu Y, Zhang Z, Rao Y, Tang Z, Xi H, Wu L, Shen S, Xue M, Xiang G, Guo X, Yang X, Hao Y, Hu Y, Li J, AO Q, Wang B, Zhang Z, Lu M, Li T. Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017). Cell Transplant 2018; 27:310-324. [PMID: 29637817 PMCID: PMC5898693 DOI: 10.1177/0963689717746999] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Revised: 07/22/2017] [Accepted: 11/13/2017] [Indexed: 12/11/2022] Open
Abstract
Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)". The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.
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Affiliation(s)
- Hongyun Huang
- Institute of Neurorestoratology, General Hospital of Armed Police Forces, Beijing, People’s Republic of China
| | - Wise Young
- W. M. Keck Center for Collaborative Neuroscience, Rutgers, State University of New Jersey, Piscataway, NJ, USA
| | - Lin Chen
- Department of Neurosurgery, Tsinghua University Yuquan Hospital, Beijing, People’s Republic of China
| | - Shiqing Feng
- Department of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
| | - Ziad M. Al Zoubi
- Jordan Ortho and Spinal Centre, Al-Saif Medical Center, Amman, Jordan
| | - Hari Shanker Sharma
- Intensive Experimental CNS Injury and Repair, University Hospital, Uppsala University, Uppsala, Sweden
| | - Hooshang Saberi
- Department of Neurosurgery, Brain and Spinal Injury Research center, Tehran University of Medical Sciences, Tehran, Iran
| | - Gustavo A. Moviglia
- Center of Research and Engineer of Tissues and Cellular Therapy, Maimonides University, Buenos Aires, Argentina
| | - Xijing He
- Department of Orthopaedics, Second Affiliated Hospital of Xi’an Jiaotong University, Xian, People’s Republic of China
| | - Dafin F. Muresanu
- Department of Neurosciences “Iuliu Hatieganu,” University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Alok Sharma
- Department of Neurosurgery, LTM Medical College, LTMG Hospital, Mumbai, Mumbai, India
| | - Ali Otom
- Royal Rehabilitation Center, King Hussein Medical Centre-RJRC Amman, Jordan
| | - Russell J. Andrews
- Nanotechnology & Smart Systems, NASA Ames Research Center, Silicon Valley, CA, USA
| | - Adeeb Al-Zoubi
- The University of Illinois College of Medicine in Peoria, Peoria, IL, USA
| | - Andrey S. Bryukhovetskiy
- NeuroVita Clinic of Interventional and Restorative Neurology and Therapy, Kashirskoye shosse, Moscow, Russia
| | - Elena R. Chernykh
- Lab of Cellular Immunotherapy, Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia
| | | | - Emad Jafar
- Jordan Ortho and Spinal Centre, Al-Saif Medical Center, Amman, Jordan
| | - W. Eustace Johnson
- Stem Cells and Regenerative Biology, Faculty of Medicine Dentistry and Life Sciences, University of Chester, Chester, United Kingdom
| | - Ying Li
- Spinal Repair Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom
| | - Daqing Li
- Spinal Repair Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom
| | - Zuo Luan
- Department of Pediatrics, Navy General Hospital of PLA, Beijing, People’s Republic of China
| | - Gengsheng Mao
- Institute of Neurorestoratology, General Hospital of Armed Police Forces, Beijing, People’s Republic of China
| | - Ashok K. Shetty
- Department of Molecular and Cellular Medicine, Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine, College Station, TX, USA
| | - Dario Siniscalco
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli,” Naples, Italy
| | - Stephen Skaper
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy
| | - Tiansheng Sun
- Department of orthopedics, PLA Army General Hospital, Beijing, People’s Republic of China
| | - Yunliang Wang
- Department of Neurology, 148th Hospital, Zibo, Shandong, People’s Republic of China
| | - Lars Wiklund
- Unit of Neurology, Department of Pharmacology and Clinical Neuroscience, Umea University, Ostersund, Sweden
| | - Qun Xue
- Department of Neurology, the First Affiliated Hospital of Soochow University, Suzhou Jiangsu, People’s Republic of China
| | - Si-Wei You
- Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China
| | - Zuncheng Zheng
- Department of Rehabilitation Medicine, The Central Hospital of Taian, Taian, Shandong, People’s Republic of China
| | | | - W. S. El Masri
- Spinal Injuries Unit, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, United Kingdom
| | - Paul R. Sanberg
- Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
| | - Qunyuan Xu
- Institute of Neuroscience, Capital Medical University, Beijing, People’s Republic of China
| | - Guoming Luan
- Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Michael Chopp
- Henry Ford Hospital, Henry Ford Health System, Neurology Research, Detroit, MI, USA
| | - Kyoung-Suok Cho
- Department of Neurosurgery, Uijongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijongbu, South Korea
| | - Xin-Fu Zhou
- Division of Health Sciences, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia
| | - Ping Wu
- Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX, USA
| | - Kai Liu
- Division of Life Science, The Hong Kong University of Science and Technology, Kowloon, Hong Kong
| | - Hamid Mobasheri
- Biomaterials Research Center, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
| | - Seiji Ohtori
- Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Hiroyuki Tanaka
- Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Fabin Han
- Centre for Stem Cells and Regenerative Medicine, Liaocheng University/Liaocheng People’s Hospital, Liaocheng, Shandong, People’s Republic of China
| | - Yaping Feng
- Department of Neurosurgery, Kunming General Hospital of Chengdu Military Command of Chinese PLA, Kunming, Yunnan, People’s Republic of China
| | - Shaocheng Zhang
- Department of Orthopedics, Changhai Hospital, The Second Military Medical University, Shanghai, People’s Republic of China
| | - Yingjie Lu
- Department of Neurosurgery, Chengde Dadu Hospital, Weichang, Hebei, People’s Republic of China
| | - Zhicheng Zhang
- Department of orthopedics, PLA Army General Hospital, Beijing, People’s Republic of China
| | - Yaojian Rao
- Department of Spinal Surgery, Luoyang Orthopedic Hospital of Henan Province, Luoyang, Henan, People’s Republic of China
| | - Zhouping Tang
- Department of Neurology, Tongji Medical College of HUST, Tongji Hospital, Wuhan, People’s Republic of China
| | - Haitao Xi
- Department of Neurology, Beijing Rehabilitation Hospital of Capital Medical University, Beijing, People’s Republic of China
| | - Liang Wu
- Center of Rehabilitation, Beijing Xiaotangshan Rehabilitation Hospital, Beijing, People’s Republic of China
| | - Shunji Shen
- Department of Rehabilitation, Weihai Municipal Hospital, Weihai, Shandong, People’s Republic of China
| | - Mengzhou Xue
- Department of Neurorehabilitation, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China
| | - Guanghong Xiang
- Brain Hospital of Hunan Province, Changsha, Hunan, People’s Republic of China
| | - Xiaoling Guo
- Department of Neurology, PLA Army 266 Hospital, Chengde, Hebei, People’s Republic of China
| | - Xiaofeng Yang
- Department of Neurosurgery, The First Affiliated Hospital of Zhejiang University Medical College, Hangzhou, Zhejiang, People’s Republic of China
| | - Yujun Hao
- Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China
| | - Yong Hu
- Department of Orthopaedic and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Jinfeng Li
- Unit of Neurology, Department of Pharmacology and Clinical Neuroscience, Umea University, Ostersund, Sweden
| | - Qiang AO
- Department of tissue engineering, China Medical University, Shenyang, Liaoning, People’s Republic of China
| | - Bin Wang
- Department of Traumatology, The Second Affiliated Hospital of Guangzhou Medical University, Haizhu District, Guangzhou, People’s Republic of China
| | - Zhiwen Zhang
- Department of Neurosurgery, First Affiliated Hospital of Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Ming Lu
- Department of Neurosurgery, Second Affiliated Hospital of Hunan Normal University (163 Hospital of PLA), Changsha, Hunan, People’s Republic of China
| | - Tong Li
- Department of Neurology, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China
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Moayeri A, Nazm Bojnordi M, Haratizadeh S, Esmaeilnejad-Moghadam A, Alizadeh R, Ghasemi Hamidabadi H. Transdifferentiation of Human Dental Pulp Stem Cells Into Oligoprogenitor Cells. Basic Clin Neurosci 2017; 8:387-394. [PMID: 29167725 PMCID: PMC5691170 DOI: 10.18869/nirp.bcn.8.5.387] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Introduction The nerve fibers in central nervous system are surrounded by myelin sheet which is formed by oligodendrocytes. Cell therapy based on oligodendrocytes and their precursors transplantation can hold a promising alternative treatment for myelin sheet repair in demyelinating diseases. Methods Human Dental Pulp Stem Cells (hDPSCs) are noninvasive, autologous and easy available source with multipotency characteristics, so they are in focus of interest in regenerative medicine. In the present study, hDPSCs were differentiated into oligoprogenitor using glial induction media, containing Retinoic Acid (RA), basic Fibroblast Growth Factor (bFGF), Platelet-Derived Growth Factor (PDGF), N2 and B27. The differentiated Oligoprogenitor Cells (OPCs) were evaluated for nestin, Olig2, NG2 and O4 using immunocytochemistry. Also, the expression of nestin, Olig2 and PDGFR-α gens (neuroprogenitor and oligoprogenitor markers) were investigated via RT-PCR technique. Results The results indicate that glial differentiation medium induces the generation of oligoprogenitor cells as revealed via exhibition of specific glial markers, including Olig2, NG2 and O4. The expersion of nestin gene (neuroprogenitor marker) and Olig2 and PDGFR-α genes (oligoprogentor markers) were detected in treated hDPSCs at the end of the induction stage. Conclusion hDPSCs can be induced to transdifferentiate into oligoprogenitor cells and respond to the routinely applied regents for glial differentiation of mesanchymal stem cells. These data suggest the hDPSCs as a valuable source for cell therapy in neurodegenerative diseases.
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Affiliation(s)
- Ardeshir Moayeri
- Department of Anatomy, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Maryam Nazm Bojnordi
- Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.,Molecular & Cell Biology Research Center, Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Sara Haratizadeh
- Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Amir Esmaeilnejad-Moghadam
- Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Rafieh Alizadeh
- ENT and Head & Neck Research Center and Department, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Hatef Ghasemi Hamidabadi
- Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.,Immunogenetic Research Center, Department of Anatomy and Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
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Song M, Lee JH, Bae J, Bu Y, Kim EC. Human Dental Pulp Stem Cells Are More Effective Than Human Bone Marrow-Derived Mesenchymal Stem Cells in Cerebral Ischemic Injury. Cell Transplant 2017; 26:1001-1016. [PMID: 28105979 DOI: 10.3727/096368916x694391] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
We compared the therapeutic effects and mechanism of transplanted human dental pulp stem cells (hDPSCs) and human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in a rat stroke model and an in vitro model of ischemia. Rats were intravenously injected with hDPSCs or hBM-MSCs 24 h after middle cerebral artery occlusion (MCAo), and both groups showed improved functional recovery and reduced infarct volume versus control rats, but the hDPSC group showed greater reduction in infarct volume than the hBM-MSC group. The positive area for the endothelial cell marker was greater in the lesion boundary areas in the hDPSC group than in the hBM-MSC group. Administration of hDPSCs to rats with stroke significantly decreased reactive gliosis, as evidenced by the attenuation of MCAo-induced GFAP+/nestin+ and GFAP+/Musashi-1+ cells, compared with hBM-MSCs. In vivo findings were confirmed by in vitro data illustrating that hDPSCs showed superior neuroprotective, migratory, and in vitro angiogenic effects in oxygen-glucose deprivation (OGD)-injured human astrocytes (hAs) versus hBM-MSCs. Comprehensive comparative bioinformatics analyses from hDPSC- and hBM-MSC-treated in vitro OGD-injured hAs were examined by RNA sequencing technology. In gene ontology and KEGG pathway analyses, significant pathways in the hDPSC-treated group were the MAPK and TGF-β signaling pathways. Thus, hDPSCs may be a better cell therapy source for ischemic stroke than hBM-MSCs.
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12
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Savitz SI, Parsha K. Enhancing Stroke Recovery with Cellular Therapies. Stroke 2016. [DOI: 10.1016/b978-0-323-29544-4.00060-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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13
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AYDIN S, YALVAÇ ME, ÖZCAN F, ŞAHİN F. Pluronic PF68 increases transfection efficiency in electroporationof mesenchymal stem cells. Turk J Biol 2016. [DOI: 10.3906/biy-1503-55] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
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14
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Solovyeva VV, Kiyasov AP, Rizvanov AA. Genetically Engineered Dental Stem Cells for Regenerative Medicine. DENTAL STEM CELLS 2016. [DOI: 10.1007/978-3-319-28947-2_5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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15
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Regenerative Applications Using Tooth Derived Stem Cells in Other Than Tooth Regeneration: A Literature Review. Stem Cells Int 2015; 2016:9305986. [PMID: 26798366 PMCID: PMC4699044 DOI: 10.1155/2016/9305986] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2015] [Revised: 09/03/2015] [Accepted: 09/08/2015] [Indexed: 12/13/2022] Open
Abstract
Tooth derived stem cells or dental stem cells are categorized according to the location from which they are isolated and represent a promising source of cells for regenerative medicine. Originally, as one kind of mesenchymal stem cells, they are considered an alternative of bone marrow stromal cells. They share many commonalties but maintain differences. Considering their original function in development and the homeostasis of tooth structures, many applications of these cells in dentistry have aimed at tooth structure regeneration; however, the application in other than tooth structures has been attempted extensively. The availability from discarded or removed teeth can be an innate benefit as a source of autologous cells. Their origin from the neural crest results in exploitation of neurological and numerous other applications. This review briefly highlights current and future perspectives of the regenerative applications of tooth derived stem cells in areas beyond tooth regeneration.
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Askari N, Yaghoobi MM, Shamsara M, Esmaeili-Mahani S. Human Dental Pulp Stem Cells Differentiate into Oligodendrocyte Progenitors Using the Expression of Olig2 Transcription Factor. Cells Tissues Organs 2015; 200:93-103. [PMID: 25966902 DOI: 10.1159/000381668] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/15/2015] [Indexed: 12/20/2022] Open
Abstract
The helix-loop-helix transcription factor Olig2 is essential for lineage determination of oligodendrocytes. Differentiation of stem cells into oligodendrocytes and transplanting them is a novel strategy for the repair of different demyelination diseases. Dental pulp stem cells (DPSCs) are of great interest in regenerative medicine due to their potential for repairing damaged tissues. In this study, DPSCs were isolated from human third molars and transfected with the human Olig2 gene as a differentiation inducer for the oligodendrogenic pathway. Following the differentiation procedure, the expression of Sox2, NG2, PDGFRα, Nestin, MBP, Olig2, Oct4, glial fibrillary acidic protein and A2B5 as stage-specific markers was studied by real-time RT-qPCR, immunocytochemistry and Western blot analysis. The cells were transplanted into a mouse model of local sciatic damage by lysolecithin as a model for demyelination. Oligodendrocyte progenitor cells (OPCs) actively remyelinated and recovered the lysolecithin-induced damages in the sciatic nerve as revealed by treadmill exercise, the von Frey filament test and hind paw withdrawal in response to a thermal stimulus. Recovery of behavioral reflexes occurred 2-6 weeks after OPC transplantation. The results demonstrate that the expression of Olig2 in DPSCs reduces the expression of stem cell markers and induces the development of oligodendrocyte progenitors as revealed by the emergence of oligodendrocyte markers. DPSCs could be programmed into oligodendrocyte progenitors and considered as a simple and valuable source for the cell therapy of neurodegenerative diseases.
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Affiliation(s)
- Nahid Askari
- National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
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17
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Taşlı PN, Doğan A, Demirci S, Şahin F. Myogenic and neurogenic differentiation of human tooth germ stem cells (hTGSCs) are regulated by pluronic block copolymers. Cytotechnology 2015; 68:319-29. [PMID: 25698158 DOI: 10.1007/s10616-014-9784-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2014] [Accepted: 08/26/2014] [Indexed: 01/26/2023] Open
Abstract
Stem cells with high proliferation, self-renewal and differentiation capacities are promising for tissue engineering approaches. Among stem cells, human tooth germ stem cells (hTGSCs) having mesenchymal stem cell characteristics are highly proliferative and able to differentiate into several cell lineages. Researchers have recently focused on transplanting stem cells with bioconductive and/or bioinductive materials that can provide cell commitment to the desired cell lineages. In the present study, effects of pluronic block copolymers (F68, F127 and P85) on in vitro myo- and neurogenic differentiation of human tooth germ stem cells (hTGSCs) were investigated. As P85 was found to exert considerable toxicity to hTGSCs even at low concentrations, it was not evaluated for further differentiation experiments. Immunocytochemical analysis, gene and protein expression studies revealed that while F68 treatment increased lineage-specific gene expression in both myo- and neuro-genically differentiated cells, F127 did not result in any remarkable difference compared to cells treated with differentiation medium. Subsequent studies are required to explore the exact mechanisms of how F68 increases the myogenic and neurogenic differentiation of hTGSCs. The present work indicates that pluronic F68 might be used in functional skeletal and neural tissue engineering applications.
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Affiliation(s)
- P Neslihan Taşlı
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, 26 Agustos Campus, Kayisdagi cad., Kayisdagi, 34755, Istanbul, Turkey
| | - Ayşegül Doğan
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, 26 Agustos Campus, Kayisdagi cad., Kayisdagi, 34755, Istanbul, Turkey.
| | - Selami Demirci
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, 26 Agustos Campus, Kayisdagi cad., Kayisdagi, 34755, Istanbul, Turkey
| | - Fikrettin Şahin
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, 26 Agustos Campus, Kayisdagi cad., Kayisdagi, 34755, Istanbul, Turkey.
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Song M, Jue SS, Cho YA, Kim EC. Comparison of the effects of human dental pulp stem cells and human bone marrow-derived mesenchymal stem cells on ischemic human astrocytes in vitro. J Neurosci Res 2015; 93:973-83. [PMID: 25663284 DOI: 10.1002/jnr.23569] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2014] [Revised: 11/27/2014] [Accepted: 01/12/2015] [Indexed: 12/11/2022]
Abstract
This study assesses the cytoprotective effects of human dental pulp stem cells (hDPSCs) and conditioned medium from hDPSCs (CM-hDPSCs) on ischemic human astrocytes (hAs) in vitro compared with human bone marrow-derived mesenchymal stem cells (hMSCs). Ischemia of hAs was induced by oxygen-glucose deprivation (OGD). CM-hDPSCs and hMSCs were collected after 48 hr of culture. Cell death was determined by 3-[4,5-dimethylthialzol-2-yl]-2,5-diphenyltetrazolium bromide and cellular ATP assays. The expression of glial fibrillary acidic protein (GFAP) and musashi-1 as markers of reactive astrogliosis was examined with immunochemical staining. mRNA expression and reactive oxygen species (ROS) were analyzed by RT-PCR and flow cytometry, respectively. OGD increased cytotoxicity in a time-dependent manner and decreased cellular ATP content concomitantly in hAs. Pretreatment and posttreatment with hDPSCs were associated with greater recovery from OGD-induced cytotoxicity in hAs compared with hMSCs. Similarly, CM-hDPSCs had a greater effect on OGD-induced cytotoxicity in a dose-dependent manner. Pre- and posttreatment with CM-hDPSCs or CM-hMSCs attenuated OGD-induced GFAP, nestin, and musashi-1 expression in hAs. Furthermore, treatment of cells with CM-hDPSCs and hMSCs blocked OGD-induced ROS production and interleukin-1ß upregulation. This study demonstrates for the first time that hDPSCs and CM-hDPSCs confer superior cytoprotection against cell death in an in vitro OGD model compared with hMSCs as shown by cell viability assay. Reactive gliosis, ROS production, and inflammatory mediators might contribute to this protective effect. Therefore, hDPSCs could represent an alternative source of cell therapy for ischemic stroke.
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Affiliation(s)
- Miyeoun Song
- Department of Oral and Maxillofacial Pathology, Research Center for Tooth and Periodontal Regeneration, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea
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Behnia A, Haghighat A, Talebi A, Nourbakhsh N, Heidari F. Transplantation of stem cells from human exfoliated deciduous teeth for bone regeneration in the dog mandibular defect. World J Stem Cells 2014; 6:505-510. [PMID: 25258673 PMCID: PMC4172680 DOI: 10.4252/wjsc.v6.i4.505] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2014] [Revised: 06/05/2014] [Accepted: 07/29/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of stem cells from human exfoliated deciduous teeth (SHED) transplanted for bone regeneration in the dog mandibular defect.
METHODS: In this prospective comparative study, SHEDs had been isolated 5 years ago from human exfoliated deciduous teeth. The undifferentiated stem cells were seeded into mandibular bone through-and-through defects of 4 dogs. Similar defects in control group were filled with cell-free collagen scaffold. After 12 wk, biopsies were taken and morphometric analysis was performed. The percentage of new bone formation and foreign body reaction were measured in each case. The data were subject to statistical analysis using the Mann-Whitney U and Kruskalwalis statistical tests. Differences at P < 0.05 was considered as significant level.
RESULTS: There were no significant differences between control and SHED-seeded groups in connective tissue (P = 0.248), woven bone (P = 0.248) and compact bone (P = 0.082). There were not any side effects in transplanted SHED group such as teratoma or malignancy and abnormalities in this period.
CONCLUSION: SHEDs which had been isolated and characterized 5 years ago and stored with cryopreservation banking were capable of proliferation and osteogenesis after 5 years, and no immune response was observed after three months of seeded SHEDs.
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20
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Effect of lactoferrin on odontogenic differentiation of stem cells derived from human 3rd molar tooth germ. Appl Biochem Biotechnol 2014; 174:2257-66. [PMID: 25173676 DOI: 10.1007/s12010-014-1204-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2014] [Accepted: 08/25/2014] [Indexed: 01/21/2023]
Abstract
Stem cell technology has been a great hope for the treatment of many common tissue regeneration-related diseases. Therefore, the main challenge in hard tissue engineering is to make a successful combination of stem cells and efficient inductors such as biomaterials or growth factors, in the concept of stem cell conversion into odontogenic cell. Even though lactoferrin has been reported to promote bone growth in vivo, the molecular mechanism of teeth formation has not been elucidated yet. Different concentrations of lactoferrin were prepared for the analysis of cell toxicity and differentiation evaluations. The odontogenic differentiation of human tooth germ stem cells (hTGSCs) was assessed by gene expression analysis, determination of protein levels in odontogenic differentiation-related protein, measuring alkaline phosphatase (ALP) activity, mineralization, and calcium deposit levels. Lactoferrin-treated group showed the highest ALP activity as opposed to the other groups which were untreated. In addition, the gene expression levels as well as the protein levels of odontogenic factors were found to be high in compared to the control groups. In the current study, it is shown for the first time that there is a significant increase in odontogenic differentiation capacity in hTGSCs when lactoferrin is applied in vitro. The study offers a considerable promise for the development of pulp regeneration by using stem cell technology combined with lactoferrin in functional tooth tissue engineering.
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Wang J, Yang W, Xie H, Song Y, Li Y, Wang L. Ischemic stroke and repair: current trends in research and tissue engineering treatments. Regen Med Res 2014; 2:3. [PMID: 25984331 PMCID: PMC4389883 DOI: 10.1186/2050-490x-2-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Accepted: 10/24/2013] [Indexed: 03/15/2023] Open
Abstract
Stroke, the third leading cause of mortality, is usually associated with severe disabilities, high recurrence rate and other poor outcomes. Currently, there are no long-term effective treatments for stroke. Cell and cytokine therapies have been explored previously. However, the therapeutic outcomes are often limited by poor survival of transplanted cells, uncontrolled cell differentiation, ineffective engraftment with host tissues and non-sustained delivery of growth factors. A tissue-engineering approach provides an alternative for treating ischemic stroke. The key design considerations for the tissue engineering approach include: choice of scaffold materials, choice of cells and cytokines and delivery methods. Here, we review current cell and biomaterial based therapies available for ischemic stroke, with a special focus on tissue-engineering strategies for regeneration of stroke-affected neuronal tissue.
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Affiliation(s)
- Jian Wang
- Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wen Yang
- Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hongjian Xie
- Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yu Song
- Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yongkui Li
- Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lin Wang
- Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China ; Medical Research Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Taşlı PN, Yalvaç ME, Sofiev N, Şahin F. Effect of F68, F127, and P85 Pluronic Block Copolymers on Odontogenic Differentiation of Human Tooth Germ Stem Cells. J Endod 2013; 39:1265-71. [DOI: 10.1016/j.joen.2013.06.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2012] [Revised: 05/15/2013] [Accepted: 06/29/2013] [Indexed: 11/28/2022]
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Effect of F68 on Cryopreservation of Mesenchymal Stem Cells Derived from Human Tooth Germ. Appl Biochem Biotechnol 2013; 171:1819-31. [DOI: 10.1007/s12010-013-0472-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2013] [Accepted: 08/22/2013] [Indexed: 11/26/2022]
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Standard recommendations for the application of Chinese clinical cell therapy for neurorestoration (2012). Cell Transplant 2013; 22 Suppl 1:S5-10. [PMID: 24044360 DOI: 10.3727/096368913x672082] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Cell therapy has been shown to be a promising alternative therapy for neurorestoration, and more than 30 different types of cells have been shown to possess some capability to restore lost or damaged neurological functions. Chinese physicians have successfully applied cell therapy to many neurological diseases and damages in the clinic and contributed to establish a discipline of neurorestoratology. To standardize the clinical procedures of cell therapy as one of the strategies for treating neurological disorders, the Chinese Branch of the International Association of Neurorestoratology (IANR) and the Preparatory Committee of Chinese Association of Neurorestoratology recently completed the Standard Recommendations (2012) for the Application of Chinese Clinical Cell Therapy for Neurorestoration. We hope these recommendations will guide clinical practice in applying cell therapy for neurorestoration, which will therein offer a reference for both Chinese and other countries' governments to make relevant official regulations. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.
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Yalvaç ME, Yarat A, Mercan D, Rizvanov AA, Palotás A, Şahin F. Characterization of the secretome of human tooth germ stem cells (hTGSCs) reveals neuro-protection by fine-tuning micro-environment. Brain Behav Immun 2013; 32:122-30. [PMID: 23517709 DOI: 10.1016/j.bbi.2013.03.007] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2013] [Revised: 03/02/2013] [Accepted: 03/11/2013] [Indexed: 12/13/2022] Open
Abstract
Bone-marrow-derived mesenchymal stem cells (MSCs) demonstrate neuro-protective effects in several disease models. By producing growth-factors, cytokines and chemokines, they promote survival of neurons in damaged brain areas. Alternative MSC sources, such as human tooth germ stem cells (hTGSCs), have been investigated for their neuro-protective properties. They ameliorate effects of neuro-toxic agents by paracrine mechanisms, however these secreted bio-active molecules are not yet characterized. Therefore, the current study aimed to provide a detailed analysis of the secretome of hTGSCs. Brain cells were exposed to various toxic materials, including Alzheimer's β-amyloid peptide (β-AP) and 6-hydroxy-dopamine (6-OHDA). When co-cultured with hTGSCs, the activity of a number of anti-oxidant enzymes (catalase, glutathione-s-transferase, glutathione-peroxidase, superoxide-dismutase) was increased and neuronal death/apoptosis was subsequently reduced. The composition of the secreted bio-active materials is influenced by various pre-existing factors such as oxygen and glucose deprivation and the age of cells (passage number). This report reveals for the first time that the neuro-protective secretome of hTGSCs and the micro-environment of cells have a mutual and dynamic impact on one another.
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Affiliation(s)
- Mehmet Emir Yalvaç
- Center for Gene Therapy, Nationwide Children's Hospital, Ohio State University, 700 Children's Drive, Columbus, OH 43205, USA.
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Martens W, Bronckaers A, Politis C, Jacobs R, Lambrichts I. Dental stem cells and their promising role in neural regeneration: an update. Clin Oral Investig 2013; 17:1969-83. [PMID: 23846214 DOI: 10.1007/s00784-013-1030-3] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2012] [Accepted: 07/01/2013] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Stem cell-based therapies are considered to be a promising treatment method for several clinical conditions such as Alzheimer's disease, Parkinson's disease, spinal cord injury, and many others. However, the ideal stem cell type for stem cell-based therapy remains to be elucidated. DISCUSSION Stem cells are present in a variety of tissues in the embryonic and adult human body. Both embryonic and adult stem cells have their advantages and disadvantages concerning the isolation method, ethical issues, or differentiation potential. The most described adult stem cell population is the mesenchymal stem cells due to their multi-lineage (trans)differentiation potential, high proliferative capacity, and promising therapeutic values. Recently, five different cell populations with mesenchymal stem cell characteristics were identified in dental tissues: dental pulp stem cells, stem cells from human exfoliated deciduous teeth, periodontal ligament stem cells, dental follicle precursor cells, and stem cells from apical papilla. CONCLUSION Each dental stem cell population possesses specific characteristics and advantages which will be summarized in this review. Furthermore, the neural characteristics of dental pulp stem cells and their potential role in (peripheral) neural regeneration will be discussed.
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Affiliation(s)
- W Martens
- Biomedical Research Institute, Laboratory of Morphology, Hasselt University, Campus Diepenbeek, Agoralaan, Building C, 3590, Diepenbeek, Belgium,
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Fang CZ, Yang YJ, Wang QH, Yao Y, Zhang XY, He XH. Intraventricular injection of human dental pulp stem cells improves hypoxic-ischemic brain damage in neonatal rats. PLoS One 2013; 8:e66748. [PMID: 23799131 PMCID: PMC3682969 DOI: 10.1371/journal.pone.0066748] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2012] [Accepted: 05/10/2013] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE To investigate the effect of intraventricular injection of human dental pulp stem cells (DPSCs) on hypoxic-ischemic brain damage (HIBD) in neonatal rats. METHODS Thirty-six neonatal rats (postnatal day 7) were assigned to control, HIBD, or HIBD+DPSC groups (n = 12 each group). For induction of HIBD, rats underwent left carotid artery ligation and were exposed to 8% to 10% oxygen for 2 h. Hoechst 33324-labeled human DPSCs were injected into the left lateral ventricle 3 days after HIBD. Behavioral assays were performed to assess hypoxic-ischemic encephalopathy (HIE), and on postnatal day 45, DPSC survival was assessed and expression of neural and glial markers was evaluated by immunohistochemistry and Western blot. RESULTS The HIBD group showed significant deficiencies compared to control on T-maze, radial water maze, and postural reflex tests, and the HIBD+DPSC group showed significant improvement on all behavioral tests. On postnatal day 45, Hoechst 33324-labeled DPSC nuclei were visible in the injected region and left cortex. Subsets of DPSCs showed immunostaining for neuronal (neuron-specific enolase [NSE], Nestin) and glial markers (glial fibrillary acidic protein [GFAP], O4). Significantly decreased staining/expression for NSE, GFAP, and O4 was found in the HBID group compared to control, and this was significantly increased in the HBID+DPSC group. CONCLUSION Intraventricular injection of human DPSCs improves HIBD in neonatal rats.
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Affiliation(s)
- Cheng-zhi Fang
- Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
- Department of Neonatology, Wuhan Children's Hospital, Wuhan, China
| | - Yu-jia Yang
- Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
- * E-mail:
| | - Qin-hong Wang
- Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
| | - Yue Yao
- Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
| | - Xiao-ying Zhang
- Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
| | - Xue-hua He
- Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
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Taşlı PN, Tapşın S, Demirel S, Yalvaç ME, Akyuz S, Yarat A, Şahin F. Isolation and Characterization of Dental Pulp Stem Cells from a Patient with Papillon–Lefèvre Syndrome. J Endod 2013; 39:31-8. [DOI: 10.1016/j.joen.2012.09.024] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2012] [Revised: 09/20/2012] [Accepted: 09/24/2012] [Indexed: 12/12/2022]
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Gong Q, Wang R, Jiang H, Lin Z, Ling J. Alteration of MicroRNA Expression of Human Dental Pulp Cells during Odontogenic Differentiation. J Endod 2012; 38:1348-54. [DOI: 10.1016/j.joen.2012.06.016] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2011] [Revised: 06/13/2012] [Accepted: 06/14/2012] [Indexed: 01/27/2023]
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Doğan A, Yalvaç ME, Şahin F, Kabanov AV, Palotás A, Rizvanov AA. Differentiation of human stem cells is promoted by amphiphilic pluronic block copolymers. Int J Nanomedicine 2012; 7:4849-60. [PMID: 23028214 PMCID: PMC3441230 DOI: 10.2147/ijn.s31949] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Stem cell usage provides novel avenues of tissue regeneration and therapeutics across disciplines. Apart from ethical considerations, the selection and amplification of donor stem cells remain a challenge. Various biopolymers with a wide range of properties have been used extensively to deliver biomolecules such as drugs, growth factors and nucleic acids, as well as to provide biomimetic surface for cellular adhesion. Using human tooth germ stem cells with high proliferation and transformation capacity, we have investigated a range of biopolymers to assess their potential for tissue engineering. Tolerability, toxicity, and their ability to direct differentiation were evaluated. The majority of pluronics, consisting of both hydrophilic and hydrophobic poly(ethylene oxide) chains, either exerted cytotoxicity or had no significant effect on human tooth germ stem cells; whereas F68 increased the multi-potency of stem cells, and efficiently transformed them into osteogenic, chondrogenic, and adipogenic tissues. The data suggest that differentiation and maturation of stem cells can be promoted by selecting the appropriate mechanical and chemical properties of polymers. It has been shown for the first time that F68, with its unique molecular characteristics, has a great potential to increase the differentiation of cells, which may lead to the development of new tissue engineering strategies in regenerative medicine.
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Affiliation(s)
- Ayşegül Doğan
- Department of Genetics and BioEngineering, College of Engineering and Architecture, Yeditepe University, Istanbul, Turkey
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31
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Gioventù S, Andriolo G, Bonino F, Frasca S, Lazzari L, Montelatici E, Santoro F, Rebulla P. A novel method for banking dental pulp stem cells. Transfus Apher Sci 2012; 47:199-206. [PMID: 22795998 DOI: 10.1016/j.transci.2012.06.005] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Dental pulp stem cells (DPSC), a cell type of mesenchymal origin showing high proliferation and plasticity, are an emerging source of adult stem cells offering interesting features in view of potential applications in regenerative medicine. These features prompted us to develop a new method to cryopreserve DPSC inside a whole tooth, thus avoiding the need to purify the cells before cryopreservation and reducing the initial costs and workload of tooth banking. In this study we cryopreserved 4 human deciduous whole teeth after digging micro-channels into the tooth with an Nd:YAG laser beam (laser piercing) to allow the cryopreservative to reach the dental pulp and preserve the cells at -80°C. Then, we isolated, expanded and characterized in vitro the stem cells after tooth thawing and mechanical fracture. In parallel, we characterized cells extracted from 2 teeth cryopreserved without laser piercing and from 4 non cryopreserved, non laser pierced, freshly fractured teeth. Our data demonstrate that DPSC isolated from laser pierced cryopreserved teeth show mesenchymal stem cells morphology, immunophenotype, viability and proliferation rate similar to those of cells isolated from fresh, non cryopreserved teeth, whereas significant loss of cell viability and proliferation rate was shown by cells isolated from teeth cryopreserved without laser piercing. These data support the use of this method for prospective whole tooth banking.
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Affiliation(s)
- Silvia Gioventù
- Department of Surgical Sciences, Reconstruction and Diagnostics, University of Milan, Faculty of Dentistry, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy
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Leone A, Volponi AA, Renton T, Sharpe PT. In-vitro regulation of odontogenic gene expression in human embryonic tooth cells and SHED cells. Cell Tissue Res 2012; 348:465-73. [PMID: 22427065 DOI: 10.1007/s00441-012-1379-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2011] [Accepted: 02/13/2012] [Indexed: 01/09/2023]
Abstract
The bud-to-cap stage transition during early tooth development is a time when the tooth-inducing potential becomes restricted to the mesenchyme. Several key genes, expressed in the mesenchyme at this stage, are an absolute requirement for the progression of tooth development. These include the transcription factors Msx1 and Pax9. The inductive potential of tooth mesenchyme cells is a key requisite for whole-tooth bioengineering and thus identification of cells that can retain this property following expansion in culture is an important as yet unresolved, goal. We show here that in-vitro culture of embryonic human tooth mesenchyme cells and SHED cells express low levels of PAX9 and MSX1 and that these levels can be significantly upregulated by activation of different signalling pathways. Such in-vitro manipulation may thus offer a simple way of maintaining/restoring/inducing the odontogenic-inducing capacity in mesenchymal cells.
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Affiliation(s)
- Angelo Leone
- BioNec, Section of Histology and Embryology, Faculty of Medicine, University of Palermo, Palermo, Italy
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Snyder BR, Cheng PH, Yang J, Yang SH, Huang AHC, Chan AWS. Characterization of dental pulp stem/stromal cells of Huntington monkey tooth germs. BMC Cell Biol 2011; 12:39. [PMID: 21910887 PMCID: PMC3189880 DOI: 10.1186/1471-2121-12-39] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2011] [Accepted: 09/12/2011] [Indexed: 12/15/2022] Open
Abstract
Background Dental pulp stem/stromal cells (DPSCs) are categorized as adult stem cells (ASCs) that retain multipotent differentiation capabilities. DPSCs can be isolated from individuals at any age and are considered to be true personal stem cells, making DPSCs one of the potential options for stem cell therapy. However, the properties of DPSCs from individuals with an inherited genetic disorder, such as Huntington's disease (HD), have not been fully investigated. Results To examine if mutant huntingtin (htt) protein impacts DPSC properties, we have established DPSCs from tooth germ of transgenic monkeys that expressed both mutant htt and green fluorescent protein (GFP) genes (rHD/G-DPSCs), and from a monkey that expressed only the GFP gene (rG-DPSCs), which served as a control. Although mutant htt and oligomeric htt aggregates were overtly present in rHD/G-DPSCs, all rHD/G-DPSCs and rG-DPSCs shared similar characteristics, including self-renewal, multipotent differentiation capabilities, expression of stemness and differentiation markers, and cell surface antigen profile. Conclusions Our results suggest that DPSCs from Huntington monkeys retain ASC properties. Thus DPSCs derived from individuals with genetic disorders such as HD could be a potential source of personal stem cells for therapeutic purposes.
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Affiliation(s)
- Brooke R Snyder
- Yerkes National Primate Research Center, 954 Gatewood Rd., NE Atlanta, GA 30329, USA
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Yalvaç ME, Yilmaz A, Mercan D, Aydin S, Dogan A, Arslan A, Demir Z, Salafutdinov II, Shafigullina AK, Sahin F, Rizvanov AA, Palotás A. Differentiation and Neuro-Protective Properties of Immortalized Human Tooth Germ Stem Cells. Neurochem Res 2011; 36:2227-35. [DOI: 10.1007/s11064-011-0546-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/07/2011] [Indexed: 01/10/2023]
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Dai M, Yang Y, Omelchenko I, Nuttall AL, Kachelmeier A, Xiu R, Shi X. Bone marrow cell recruitment mediated by inducible nitric oxide synthase/stromal cell-derived factor-1alpha signaling repairs the acoustically damaged cochlear blood-labyrinth barrier. THE AMERICAN JOURNAL OF PATHOLOGY 2010; 177:3089-99. [PMID: 21057001 DOI: 10.2353/ajpath.2010.100340] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Using a mouse model with noise-induced cochlear blood-labyrinth-barrier (CBLB) injury, we examined the effects of inducible nitric oxide synthase (iNOS) on the recruitment of bone marrow-derived cells (BMDCs) to the CBLB after acoustic injury. Lethally irradiated C57BL/6J and B6.129P2-Nos2(tm1Lau)/J mice were transplanted with GFP(+)-BMDCs from C57Bl/6-Tg (UBC GFP) mice. Four weeks after transplantation, we assessed the population of GFP(+)-BMDCs in the CBLB. Only small numbers of GFP(+)-BMDCs were found to infiltrate the area of the CBLB in the control recipient mice. However, robust GFP(+)-BMDC migration occurred in the area of the CBLB within the injured cochlea during the first week following acoustic trauma, and further BMDC accumulation was seen by 2 weeks posttrauma. After 4 weeks, the BMDCs were integrated into vessels. Local iNOS from perivascular resident macrophages was found to be important for BMDC infiltration, since mice deficient in iNOS (Inos(-/-)) and mice with iNOS that had been inhibited by 1400W displayed reduced BMDC infiltration. Stromal cell-derived factor-1α (SDF-1α) and its chemokine receptor 4 (CXCR4) were required for the iNOS-triggered recruitment. BMDC recruitment was significantly reduced by the inhibition of SDF-1α activity. Inhibition of the iNOS/SDF-1α signaling pathway reduced vascular repair as observed by reduced vascular density. Our study revealed an intrinsic signaling pathway of iNOS that mediates SDF-1α to promote GFP(+)-BMDC infiltration/targeting in cochlear vascular repair.
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Affiliation(s)
- Min Dai
- Oregon Hearing Research Center, Department of Otolaryngology and Head and Neck Surgery, Oregon Health and Science University, Portland, OR 97239, USA
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Stem cell-based biological tooth repair and regeneration. Trends Cell Biol 2010; 20:715-22. [PMID: 21035344 PMCID: PMC3000521 DOI: 10.1016/j.tcb.2010.09.012] [Citation(s) in RCA: 188] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2010] [Revised: 09/27/2010] [Accepted: 09/28/2010] [Indexed: 12/18/2022]
Abstract
Teeth exhibit limited repair in response to damage, and dental pulp stem cells probably provide a source of cells to replace those damaged and to facilitate repair. Stem cells in other parts of the tooth, such as the periodontal ligament and growing roots, play more dynamic roles in tooth function and development. Dental stem cells can be obtained with ease, making them an attractive source of autologous stem cells for use in restoring vital pulp tissue removed because of infection, in regeneration of periodontal ligament lost in periodontal disease, and for generation of complete or partial tooth structures to form biological implants. As dental stem cells share properties with mesenchymal stem cells, there is also considerable interest in their wider potential to treat disorders involving mesenchymal (or indeed non-mesenchymal) cell derivatives, such as in Parkinson's disease.
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