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Therapeutic potential of dental pulp stem cell transplantation in a rat model of Alzheimer’s disease

Neural Regeneration Research 2021年第5期16卷 893-898页

作者： Xue-Mei Zhang Yuan-Jiao Ouyang Bing-Qian Yu Wei Li Mei-Yu Yu Jin-Yue Li Zhuo-Min Jiao Dan Yang Na Li Ying Shi Yun-Yun Xu Zhi-Jun He Duo Wang Hui Yue Jin Fu Department of Neurology The 2nd Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Department of Neurology Ningbo Hangzhou Bay HospitalNingboZhejiang ProvinceChina Department of Neurology the First Hospital of QiqiharQiqiharHeilongjiang ProvinceChina

dental pulp stem cells are dental pulp-derived mesenchymal stem cells that originate from the neural *** exhibit greater potential for the treatment of nervous system diseases than other types of stem cells because of their neurogenic differentiation capability and their ability to secrete multiple neurotrophic *** studies have reported Alzheimer’s disease treatment using dental pulp stem *** models of Alzheimer’s disease were established by injecting amyloid-β1–42 into the *** days later,5×106 dental pulp stem cells were injected into the *** and western blot assays showed that dental pulp stem cell transplantation increased the expression of neuron-related doublecortin,NeuN,and neurofilament 200 in the hippocampus,while the expression of amyloid-βwas ***,cognitive and behavioral abilities were *** findings indicate that dental pulp stem cell transplantation in rats can improve cognitive function by regulating the secretion of neuron-related proteins,which indicates a potential therapeutic effect for Alzheimer’s *** study was approved by the Animal Ethics Committee of Harbin Medical University,China(approval ***2017-132)on February 21,2017.

关键词： Alzheimer’s disease brain central nervous system dental pulp stem cell in vivo model rat stem cells transplantation

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dental pulp stem cells stimulate neuronal differentiation of PC12 cells

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Neural Regeneration Research 2021年第9期16卷 1821-1828页

作者： Nessma Sultan Laila E.Amin Ahmed R.Zaher Mohammed E.Grawish Ben A.Scheven School of Dentistry Oral BiologyCollege of Medical and Dental SciencesUniversity of BirminghamBirminghamUK Department of Oral Biology Faculty of DentistryMansoura UniversityEgypt Faculty of Dentistry Horus UniversityNew DamiettaEgypt Department of Oral Biology Faculty of Oral and Dental MedicineDelta University for Science and TechnologyMansouraEgypt

dental pulp stem cells(DPSCs) secrete neurotrophic factors which may play an important therapeutic role in neural development, maintenance and repair. To test this hypothesis, DPSCs-conditioned medium(DPSCs-CM) was collected from 72 hours serum-free DPSCs cultures. The impact of DPSCs-derived factors on PC12 survival, growth, migration and differentiation was investigated. PC12 cells were treated with nerve growth factor(NGF), DPSCs-CM or co-cultured with DPSCs using Transwell inserts for 8 days. The number of surviving cells with neurite outgrowths and the length of neurites were measured by image analysis. Immunocytochemical staining was used to evaluate the expression of neuronal markers NeuN, microtubule associated protein 2(MAP-2) and cytoskeletal marker βIII-tubulin. Gene expression levels of axonal growth-associated protein 43 and synaptic protein Synapsin-I, NeuN, MAP-2 and βIII-tubulin were analysed by quantitative polymerase chain reaction(qRT-PCR). DPSCs-CM was analysed for the neurotrophic factors(NGF, brain-derived neurotrophic factor [BDNF], neurotrophin-3, and glial cell-derived neurotrophic factor [GDNF]) by specific ELISAs. Specific neutralizing antibodies against the detected neurotrophic factors were used to study their exact role on PC12 neuronal survival and neurite outgrowth extension. DPSCs-CM significantly promoted cell survival and induced the neurite outgrowth confirmed by NeuN, MAP-2 and βIII-tubulin immunostaining. Furthermore, DPSCsCM was significantly more effective in stimulating PC12 neurite outgrowths than live DPSCs/PC12 co-cultures over the time studied. The morphology of induced PC12 cells in DPSCs-CM was similar to NGF positive controls;however, DPSCs-CM stimulation of cell survival was significantly higher than what was seen in NGF-treated cultures. The number of surviving PC12 cells treated with DPSCs-CM was markedly reduced by the addition of anti-GDNF, whilst PC12 neurite outgrowth was significantly attenuated by anti-NGF, an

关键词： brain-derived neurotrophic factor conditioned medium dental pulp stem cell glial cell line-derived nerve growth factor neurite outgrowth neurotrophic factor neurotrophin-3 phaeochromocytoma PC12 cell

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Human dental pulp stem cells express many pluripotency regulators and differentiate into neuronal cells

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Neural Regeneration Research 2011年第34期6卷 2666-2672页

作者： Behnam Ebrahimi Mohammad Mehdi Yaghoobi Ali Mohammadi Kamal-abadi Maryam Raoofn Departmentof Biotechnology Research Institute for Environmental Sciences International Centre for Science High Technology and Environmental Sciences Kerman Iran Department of Biology Faculty of Sciences Shahid Bahonar University of Kerman Kerman Ira Oral and dental Diseases Research Center/Department of Endodontics Kerman University of Medical Sciences Kerman Iran

stem cells were isolated from human dental pulp using an optimized method, in which pulp pieces were digested by enzymes and immobilized to enhance cell outgrowth. stem cell marker expression was detected by reverse transcription-PCR （RT-PCR）, and differentiation markers were detected by real-time quantitative RT-PCR and immunocytochemistry. Results showed that dental pulp stem cells actively expressed nanog, oct4, nucleostemin slain-l, jmjdla, jmjd2c, and cyclin DI. When stem cells were induced to differentiate into neurons, nucleostemin, nanog, and cyclin D1 expression significantly decreased, whereas expression of neuronal markers, such as microtubule associated protein-2 and neurofilament-heavy, significantly increased. These results suggested that stem cells exited a pluripotent state and entered a neuronal differentiation pathway. In addition, results demonstrated that human dental pulp serves as a reservoir of stem cells that express defined stem cell markers; these cells were easily isolated and were induced to differentiate towards a desired cell lineage.

关键词： dental pulp stem cell neural regeneration neuronal differentiation PluriNet real-time quantitative reverse transcription polymerase chain reaction stem cell marker

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Hypoxia response element-directed expression of bFGF in dental pulp stem cells improve the hypoxic environment by targeting pericytes in SCI rats

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Bioactive Materials 2021年第8期6卷 2452-2466页

作者： Sipin Zhu Yibo Ying Yan He Xingxing Zhong Jiahui Ye Zhiyang Huang Min Chen Qiuji Wu Yifan Zhang Ziyue Xiang Yurong Tu Weiyang Ying Jian Xiao Xiaokun Li Qingsong Ye Zhouguang Wang Department of Orthopaedics The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang325000China Molecular Pharmacology Research Center School of Pharmaceutical ScienceWenzhou Medical UniversityWenzhouZhejiangChina Department of Pain Medicine The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou325000ZhejiangChina School and Hospital of Stomatology Wenzhou Medical UniversityWenzhou325035China Laboratory of Regenerative Medicine Tianyou HospitalWuhan University of Science and TechnologyWuhan430064China The Department of Cardiology The First Affiliated HospitalSchool of MedicineZhejiang UniversityChina Massachusetts General Hospital Harvard UniversityBoston02114USA Research Units of Clinical Translation of cell Growth Factors and Diseases Research Chinese Academy of Medical ScienceChina Center of Regenerative Medicine Renmin Hospital of Wuhan UniversityWuhan630060China

cell-based transplantation strategies possess great potential for spinal cord injury(SCI)*** fibroblast growth factor(bFGF)has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following *** dental pulp stem cells(DPSCs)are abundant stem cells with low immune rejection,which can be considered for cell replacement *** purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements(5HRE)using an adeno-associated virus(AAV-5HRE-bFGF-DPSCs)in SCI repairing *** this study,DPSCs were revealed to differentiate into CD13^(+)pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13^(+)pericytes to vascular endothelial *** re-attachment of CD13^(+)pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of *** a result,increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was ***,this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.

关键词： Spinal cord injury Adeno-associated virus Basic fibroblast growth factor dental pulp stem cell Vascular regulation Hypoxic microenvironment

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