The Experts below are selected from a list of 5100 Experts worldwide ranked by ideXlab platform
Misako Nakashima - One of the best experts on this subject based on the ideXlab platform.
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animal models for stem cell based Pulp Regeneration foundation for human clinical applications
Tissue Engineering Part B-reviews, 2019Co-Authors: Misako Nakashima, Koichiro Iohara, Jacques E Nor, Ashraf F Fouad, Marco C Bottino, George T.-j. HuangAbstract:Rapid progress has been made in the last decade related to stem cell-mediated Pulp–dentin Regeneration, from characterization of dental Pulp stem cells (DPSCs) to the first-ever reported clinical c...
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Pulp Regeneration by transplantation of dental Pulp stem cells in Pulpitis a pilot clinical study
Stem Cell Research & Therapy, 2017Co-Authors: Misako Nakashima, Koichiro Iohara, Masashi Murakami, Hiroshi Nakamura, Yayoi Sato, Yoshiko Ariji, Kenji MatsushitaAbstract:Experiments have previously demonstrated the therapeutic potential of mobilized dental Pulp stem cells (MDPSCs) for complete Pulp Regeneration. The aim of the present pilot clinical study is to assess the safety, potential efficacy, and feasibility of autologous transplantation of MDPSCs in Pulpectomized teeth. Five patients with irreversible Pulpitis were enrolled and monitored for up to 24 weeks following MDPSC transplantation. The MDPSCs were isolated from discarded teeth and expanded based on good manufacturing practice (GMP). The quality of the MDPSCs at passages 9 or 10 was ascertained by karyotype analyses. The MDPSCs were transplanted with granulocyte colony-stimulating factor (G-CSF) in atelocollagen into Pulpectomized teeth. The clinical and laboratory evaluations demonstrated no adverse events or toxicity. The electric Pulp test (EPT) of the Pulp at 4 weeks demonstrated a robust positive response. The signal intensity of magnetic resonance imaging (MRI) of the regenerated tissue in the root canal after 24 weeks was similar to that of normal dental Pulp in the untreated control. Finally, cone beam computed tomography demonstrated functional dentin formation in three of the five patients. Human MDPSCs are safe and efficacious for complete Pulp Regeneration in humans in this pilot clinical study.
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trophic effects and regenerative potential of mobilized mesenchymal stem cells from bone marrow and adipose tissue as alternative cell sources for Pulp dentin Regeneration
Cell Transplantation, 2015Co-Authors: Masashi Murakami, K. Iohara, Yuki Hayashi, Yohei Osako, Yujiro Hirose, Misako NakashimaAbstract:Dental Pulp stem cell (DPSC) subsets mobilized by granulocyte-colony-stimulating factor (G-CSF) are safe and efficacious for complete Pulp Regeneration. The supply of autologous Pulp tissue, however, is very limited in the aged. Therefore, alternative sources of mesenchymal stem/progenitor cells (MSCs) are needed for the cell therapy. In this study, DPSCs, bone marrow (BM), and adipose tissue (AD)-derived stem cells of the same individual dog were isolated using G-CSF-induced mobilization (MDPSCs, MBMSCs, and MADSCs). The positive rates of CXCR4 and G-CSFR in MDPSCs were similar to MADSCs and were significantly higher than those in MBMSCs. Trophic effects of MDPSCs on angiogenesis, neurite extension, migration, and antiapoptosis were higher than those of MBMSCs and MADSCs. Pulp-like loose connective tissues were regenerated in all three MSC transplantations. Significantly higher volume of regenerated Pulp and higher density of vascularization and innervation were observed in response to MDPSCs compared to MBMSC and MADSC transplantation. Collagenous matrix containing dentin sialophosphoprotein (DSPP)-positive odontoblast-like cells was the highest in MBMSCs and significantly higher in MADSCs compared to MDPSCs. MBMSCs and MADSCs, therefore, have potential for Pulp Regeneration, although the volume of regenerated Pulp tissue, angiogenesis, and reinnervation, were less. Thus, in conclusion, an alternative cell source for dental Pulp/dentin Regeneration are stem cells from BM and AD tissue.
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age dependent decline in dental Pulp Regeneration after Pulpectomy in dogs
Experimental Gerontology, 2014Co-Authors: Koichiro Iohara, Masashi Murakami, Kazuhiko Nakata, Misako NakashimaAbstract:The age-associated decline in the regenerative abilities of mesenchymal stem cells (MSCs) may be due to age-related changes in reduction in number, intrinsic properties of MSCs and extrinsic factors of the extracellular environment (the stem cell niche). The effect of age on the efficacy of MSC transplantation on Regeneration, however, has not been clearly demonstrated due to variable methods of isolation of MSCs and variations in stem cell populations. In this study, dental Pulp stem cell (DPSC) subsets were isolated from young and aged dog teeth based on their migratory response to granulocyte-colony stimulating factor (G-CSF) (MDPSCs). In order to study the age-associated changes, their biological properties and stability were compared and the regenerative potential was examined in a Pulpectomized tooth model in aged dogs. MDPSCs from aged dogs were efficiently enriched in stem cells, expressing trophic factors with high proliferation, migration and anti-apoptotic effects as in MDPSCs from young dogs. However, Pulp Regeneration was retarded 120 days after autologous transplantation of aged MDPSCs. We further demonstrated that isolated periodontal ligament stem cells (PDLSCs) from aged dogs, representative of migrating stem cells from outside of the tooth compartment to regenerate Pulp tissue, had lower proliferation, migration and anti-apoptotic abilities. These results therefore provide a better understanding of the mechanisms involved in the age-dependent decline in Pulp Regeneration, which are attributed to a decrease in the regenerative potential of resident stem cells.
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mobilized dental Pulp stem cells for Pulp Regeneration initiation of clinical trial
Journal of Endodontics, 2014Co-Authors: Misako Nakashima, Koichiro IoharaAbstract:Stem cell therapy is a potential strategy to regenerate the dentin-Pulp complex, enabling the conservation and restoration of functional teeth. We assessed the efficacy and safety of Pulp stem cell transplantation as a prelude before the initiation of clinical trials. Granulocyte-colony stimulating factor (G-CSF) induces subsets of dental Pulp stem cells to form mobilized dental Pulp stem cells (MDPSCs). Good manufacturing practice is a prerequisite for the isolation and expansion of MDPSCs that are enriched in stem cells, expressing a high level of trophic factors with properties of high proliferation, migration, and antiapoptotic effects and endowed with regenerative potential. The quality of clinical-grade MDPSCs was assured by the absence of abnormalities/aberrations in karyotype and the lack of tumor formation after transplantation in immunodeficient mice. Autologous transplantation of MDPSCs with G-CSF in Pulpectomized teeth in dogs augmented the Regeneration of Pulp tissue. The combinatorial trophic effects of MDPSCs and G-CSF on cell migration, antiapoptosis, immunosuppression, and neurite outgrowth were also confirmed in vitro. Furthermore, MDPSCs from the aged donors were as potent as the young donors. It is noteworthy that there were no significant age-related changes in biological properties such as stability, regenerative potential, and expression of the senescence markers in MDPSCs. On the other hand, autologous transplantation of MDPSCs with G-CSF induced less regenerated Pulp tissue in the aged dogs compared with the young dogs. In conclusion, the preclinical safety, feasibility, and efficacy of Pulp Regeneration by MDPSCs and G-CSF were established. Therefore, the standardization and establishment of regulatory guidelines for stem cell therapy in clinical endodontics is now a reality.
Koichiro Iohara - One of the best experts on this subject based on the ideXlab platform.
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animal models for stem cell based Pulp Regeneration foundation for human clinical applications
Tissue Engineering Part B-reviews, 2019Co-Authors: Misako Nakashima, Koichiro Iohara, Jacques E Nor, Ashraf F Fouad, Marco C Bottino, George T.-j. HuangAbstract:Rapid progress has been made in the last decade related to stem cell-mediated Pulp–dentin Regeneration, from characterization of dental Pulp stem cells (DPSCs) to the first-ever reported clinical c...
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Pulp Regeneration by transplantation of dental Pulp stem cells in Pulpitis a pilot clinical study
Stem Cell Research & Therapy, 2017Co-Authors: Misako Nakashima, Koichiro Iohara, Masashi Murakami, Hiroshi Nakamura, Yayoi Sato, Yoshiko Ariji, Kenji MatsushitaAbstract:Experiments have previously demonstrated the therapeutic potential of mobilized dental Pulp stem cells (MDPSCs) for complete Pulp Regeneration. The aim of the present pilot clinical study is to assess the safety, potential efficacy, and feasibility of autologous transplantation of MDPSCs in Pulpectomized teeth. Five patients with irreversible Pulpitis were enrolled and monitored for up to 24 weeks following MDPSC transplantation. The MDPSCs were isolated from discarded teeth and expanded based on good manufacturing practice (GMP). The quality of the MDPSCs at passages 9 or 10 was ascertained by karyotype analyses. The MDPSCs were transplanted with granulocyte colony-stimulating factor (G-CSF) in atelocollagen into Pulpectomized teeth. The clinical and laboratory evaluations demonstrated no adverse events or toxicity. The electric Pulp test (EPT) of the Pulp at 4 weeks demonstrated a robust positive response. The signal intensity of magnetic resonance imaging (MRI) of the regenerated tissue in the root canal after 24 weeks was similar to that of normal dental Pulp in the untreated control. Finally, cone beam computed tomography demonstrated functional dentin formation in three of the five patients. Human MDPSCs are safe and efficacious for complete Pulp Regeneration in humans in this pilot clinical study.
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similar in vitro effects and Pulp Regeneration in ectopic tooth transplantation by basic fibroblast growth factor and granulocyte colony stimulating factor
Oral Diseases, 2015Co-Authors: Norio Takeuchi, Koichiro Iohara, Masashi Murakami, Yuki Hayashi, Hiroshi Nakamura, Kazuhiko Nakata, F J Alvarez, Hiroshi Horibe, M NakashimaAbstract:Objectives Granulocyte-colony stimulating factor (G-CSF) has been shown to have combinatorial trophic effects with dental Pulp stem cells for Pulp Regeneration. The aim of this investigation is to examine the effects of basic fibroblast growth factor (bFGF) in vitro and in vivo compared with those of G-CSF and to assess the potential utility of bFGF as an alternative to G-CSF for Pulp Regeneration. Materials and methods Five different types of cells were examined in the in vitro effects of bFGF on cell migration, proliferation, anti-apoptosis, neurite outgrowth, angiogenesis, and odontogenesis compared with those of G-CSF. The in vivo regenerative potential of Pulp tissue including vasculogenesis and odontoblastic differentiation was also compared using an ectopic tooth transplantation model. Results Basic fibroblast growth factor was similar to G-CSF in high migration, proliferation and anti-apoptotic effects and angiogenic and neurite outgrowth stimulatory activities in vitro. There was no significant difference between bFGF and G-CSF in the regenerative potential in vivo. Conclusions The potential utility of bFGF for Pulp Regeneration is demonstrated as a homing/migration factor similar to the influence of G-CSF.
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age dependent decline in dental Pulp Regeneration after Pulpectomy in dogs
Experimental Gerontology, 2014Co-Authors: Koichiro Iohara, Masashi Murakami, Kazuhiko Nakata, Misako NakashimaAbstract:The age-associated decline in the regenerative abilities of mesenchymal stem cells (MSCs) may be due to age-related changes in reduction in number, intrinsic properties of MSCs and extrinsic factors of the extracellular environment (the stem cell niche). The effect of age on the efficacy of MSC transplantation on Regeneration, however, has not been clearly demonstrated due to variable methods of isolation of MSCs and variations in stem cell populations. In this study, dental Pulp stem cell (DPSC) subsets were isolated from young and aged dog teeth based on their migratory response to granulocyte-colony stimulating factor (G-CSF) (MDPSCs). In order to study the age-associated changes, their biological properties and stability were compared and the regenerative potential was examined in a Pulpectomized tooth model in aged dogs. MDPSCs from aged dogs were efficiently enriched in stem cells, expressing trophic factors with high proliferation, migration and anti-apoptotic effects as in MDPSCs from young dogs. However, Pulp Regeneration was retarded 120 days after autologous transplantation of aged MDPSCs. We further demonstrated that isolated periodontal ligament stem cells (PDLSCs) from aged dogs, representative of migrating stem cells from outside of the tooth compartment to regenerate Pulp tissue, had lower proliferation, migration and anti-apoptotic abilities. These results therefore provide a better understanding of the mechanisms involved in the age-dependent decline in Pulp Regeneration, which are attributed to a decrease in the regenerative potential of resident stem cells.
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mobilized dental Pulp stem cells for Pulp Regeneration initiation of clinical trial
Journal of Endodontics, 2014Co-Authors: Misako Nakashima, Koichiro IoharaAbstract:Stem cell therapy is a potential strategy to regenerate the dentin-Pulp complex, enabling the conservation and restoration of functional teeth. We assessed the efficacy and safety of Pulp stem cell transplantation as a prelude before the initiation of clinical trials. Granulocyte-colony stimulating factor (G-CSF) induces subsets of dental Pulp stem cells to form mobilized dental Pulp stem cells (MDPSCs). Good manufacturing practice is a prerequisite for the isolation and expansion of MDPSCs that are enriched in stem cells, expressing a high level of trophic factors with properties of high proliferation, migration, and antiapoptotic effects and endowed with regenerative potential. The quality of clinical-grade MDPSCs was assured by the absence of abnormalities/aberrations in karyotype and the lack of tumor formation after transplantation in immunodeficient mice. Autologous transplantation of MDPSCs with G-CSF in Pulpectomized teeth in dogs augmented the Regeneration of Pulp tissue. The combinatorial trophic effects of MDPSCs and G-CSF on cell migration, antiapoptosis, immunosuppression, and neurite outgrowth were also confirmed in vitro. Furthermore, MDPSCs from the aged donors were as potent as the young donors. It is noteworthy that there were no significant age-related changes in biological properties such as stability, regenerative potential, and expression of the senescence markers in MDPSCs. On the other hand, autologous transplantation of MDPSCs with G-CSF induced less regenerated Pulp tissue in the aged dogs compared with the young dogs. In conclusion, the preclinical safety, feasibility, and efficacy of Pulp Regeneration by MDPSCs and G-CSF were established. Therefore, the standardization and establishment of regulatory guidelines for stem cell therapy in clinical endodontics is now a reality.
Xiaohua Liu - One of the best experts on this subject based on the ideXlab platform.
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multifunctional peptide conjugated nanocarriers for Pulp Regeneration in a full length human tooth root
Acta Biomaterialia, 2021Co-Authors: Yongxi Liang, Yi Hong, Xiaohua LiuAbstract:Dental Pulp is a highly vascularized tissue, situated in an inextensible environment surrounded by rigid dentinal walls. The Pulp receives its blood supply solely from the small apical foramen of a tooth root. Due to the unique anatomy that controls nutrition supply, Regeneration of Pulp tissue in a full-length tooth root has long been a challenge in regenerative endodontics. In this study, we designed and synthesized a multifunctional peptide-conjugated, pH-sensitive, non-viral gene vector for fast revascularization and Pulp Regeneration in a full-length human tooth root. The multifunctional peptide was designed to have distinctive features, including a cell-penetrating peptide to enhance cellular uptake, a nuclear localization signal peptide to assist in the translocation of an angiogenic gene into the nucleus, and a fluorescent tryptophan residue to visualize and quantify the transfection efficiency. Furthermore, a pH-sensitive dimethylmaleic anhydride (DMA) was integrated with the multifunctional peptide to enhance the transfected gene complex to escape from endosomes/lysosomes after internalization. In vitro experiments showed that the multifunctional non-viral gene vector significantly increased internalization and gene transfection efficiency as well as reduced cytotoxicity. After dental Pulp stem cells (DPSCs) were transfected with the multifunctional gene vector/pVEGF complexes, the expression of VEGF from the DPSCs was upregulated for more than eight folds, which in turn greatly enhanced endothelial cell migration and vascular-like tube formation. Six weeks after implantation, the VEGF-transfected DPSCs accelerated new blood vessel formation and the regenerated Pulp tissue occupied most of the area in the canal of a full-length human tooth root. The multifunctional peptide conjugated non-viral gene delivery is a safe and effective approach for regenerative endodontics. STATEMENT OF SIGNIFICANCE: Pulp Regeneration in a full-length tooth root canal has long been a challenge in regenerative endodontics. This is due to the unique root anatomy that allows the blood supply of the tooth root only from a small apical foramen (< 1 mm), leading to a severe barrier for revascularization during Pulp Regeneration. In this work, we designed a multifunctional peptide-conjugated, pH-sensitive, non-viral gene vector to address this challenge. Our work shows that the peptide-conjugated system was an excellent carrier for fast revascularization and Pulp tissue Regeneration in a full-length toot root. This study will interest the multidisciplinary readership in gene delivery, biomaterials, and dental/craniofacial tissue engineering community.
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multifunctional peptide conjugated nanocarriers for Pulp Regeneration in a full length human tooth root
Social Science Research Network, 2021Co-Authors: Yongxi Liang, Yi Hong, Xiaohua LiuAbstract:Dental Pulp is a highly vascularized tissue, situated in an inextensible environment surrounded by rigid dentinal walls. The Pulp receives its blood supply solely from the small apical foramen of a tooth root. Due to the unique anatomy that controls nutrition supply, Regeneration of Pulp tissue in a full-length tooth root has long been a challenge in regenerative endodontics. In this study, we designed and synthesized a novel multifunctional peptide-conjugated, pH-sensitive, non-viral gene vector for fast revascularization and Pulp Regeneration in a full-length human tooth root. The multifunctional peptide was designed to have distinctive features, including a cell-penetrating peptide to enhance cellular uptake, a nuclear localization signal peptide to assist in the translocation of an angiogenic gene into the nucleus, and a fluorescent tryptophan residue to visualize and quantify the transfection efficiency. Furthermore, a pH-sensitive dimethylmaleic anhydride (DMA) was integrated with the multifunctional peptide to enhance the transfected gene complex to escape from endosomes/lysosomes after internalization. In vitro experiments showed that the multifunctional non-viral gene vector significantly increased internalization and gene transfection efficiency as well as reduced cytotoxicity. After dental Pulp stem cells (DPSCs) were transfected with the multifunctional gene vector/pVEGF complexes, the expression of VEGF from the DPSCs was upregulated for more than eight folds, which in turn greatly enhanced endothelial cell migration and vascular-like tube formation. Six weeks after implantation, the VEGF-transfected DPSCs accelerated new blood vessel formation and the regenerated Pulp tissue occupied most of the area in the canal of a full-length human tooth root. The multifunctional peptide conjugated non-viral gene delivery is a safe and effective approach for regenerative endodontics.
Masashi Murakami - One of the best experts on this subject based on the ideXlab platform.
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Pulp Regeneration by transplantation of dental Pulp stem cells in Pulpitis a pilot clinical study
Stem Cell Research & Therapy, 2017Co-Authors: Misako Nakashima, Koichiro Iohara, Masashi Murakami, Hiroshi Nakamura, Yayoi Sato, Yoshiko Ariji, Kenji MatsushitaAbstract:Experiments have previously demonstrated the therapeutic potential of mobilized dental Pulp stem cells (MDPSCs) for complete Pulp Regeneration. The aim of the present pilot clinical study is to assess the safety, potential efficacy, and feasibility of autologous transplantation of MDPSCs in Pulpectomized teeth. Five patients with irreversible Pulpitis were enrolled and monitored for up to 24 weeks following MDPSC transplantation. The MDPSCs were isolated from discarded teeth and expanded based on good manufacturing practice (GMP). The quality of the MDPSCs at passages 9 or 10 was ascertained by karyotype analyses. The MDPSCs were transplanted with granulocyte colony-stimulating factor (G-CSF) in atelocollagen into Pulpectomized teeth. The clinical and laboratory evaluations demonstrated no adverse events or toxicity. The electric Pulp test (EPT) of the Pulp at 4 weeks demonstrated a robust positive response. The signal intensity of magnetic resonance imaging (MRI) of the regenerated tissue in the root canal after 24 weeks was similar to that of normal dental Pulp in the untreated control. Finally, cone beam computed tomography demonstrated functional dentin formation in three of the five patients. Human MDPSCs are safe and efficacious for complete Pulp Regeneration in humans in this pilot clinical study.
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trophic effects and regenerative potential of mobilized mesenchymal stem cells from bone marrow and adipose tissue as alternative cell sources for Pulp dentin Regeneration
Cell Transplantation, 2015Co-Authors: Masashi Murakami, K. Iohara, Yuki Hayashi, Yohei Osako, Yujiro Hirose, Misako NakashimaAbstract:Dental Pulp stem cell (DPSC) subsets mobilized by granulocyte-colony-stimulating factor (G-CSF) are safe and efficacious for complete Pulp Regeneration. The supply of autologous Pulp tissue, however, is very limited in the aged. Therefore, alternative sources of mesenchymal stem/progenitor cells (MSCs) are needed for the cell therapy. In this study, DPSCs, bone marrow (BM), and adipose tissue (AD)-derived stem cells of the same individual dog were isolated using G-CSF-induced mobilization (MDPSCs, MBMSCs, and MADSCs). The positive rates of CXCR4 and G-CSFR in MDPSCs were similar to MADSCs and were significantly higher than those in MBMSCs. Trophic effects of MDPSCs on angiogenesis, neurite extension, migration, and antiapoptosis were higher than those of MBMSCs and MADSCs. Pulp-like loose connective tissues were regenerated in all three MSC transplantations. Significantly higher volume of regenerated Pulp and higher density of vascularization and innervation were observed in response to MDPSCs compared to MBMSC and MADSC transplantation. Collagenous matrix containing dentin sialophosphoprotein (DSPP)-positive odontoblast-like cells was the highest in MBMSCs and significantly higher in MADSCs compared to MDPSCs. MBMSCs and MADSCs, therefore, have potential for Pulp Regeneration, although the volume of regenerated Pulp tissue, angiogenesis, and reinnervation, were less. Thus, in conclusion, an alternative cell source for dental Pulp/dentin Regeneration are stem cells from BM and AD tissue.
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similar in vitro effects and Pulp Regeneration in ectopic tooth transplantation by basic fibroblast growth factor and granulocyte colony stimulating factor
Oral Diseases, 2015Co-Authors: Norio Takeuchi, Koichiro Iohara, Masashi Murakami, Yuki Hayashi, Hiroshi Nakamura, Kazuhiko Nakata, F J Alvarez, Hiroshi Horibe, M NakashimaAbstract:Objectives Granulocyte-colony stimulating factor (G-CSF) has been shown to have combinatorial trophic effects with dental Pulp stem cells for Pulp Regeneration. The aim of this investigation is to examine the effects of basic fibroblast growth factor (bFGF) in vitro and in vivo compared with those of G-CSF and to assess the potential utility of bFGF as an alternative to G-CSF for Pulp Regeneration. Materials and methods Five different types of cells were examined in the in vitro effects of bFGF on cell migration, proliferation, anti-apoptosis, neurite outgrowth, angiogenesis, and odontogenesis compared with those of G-CSF. The in vivo regenerative potential of Pulp tissue including vasculogenesis and odontoblastic differentiation was also compared using an ectopic tooth transplantation model. Results Basic fibroblast growth factor was similar to G-CSF in high migration, proliferation and anti-apoptotic effects and angiogenic and neurite outgrowth stimulatory activities in vitro. There was no significant difference between bFGF and G-CSF in the regenerative potential in vivo. Conclusions The potential utility of bFGF for Pulp Regeneration is demonstrated as a homing/migration factor similar to the influence of G-CSF.
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age dependent decline in dental Pulp Regeneration after Pulpectomy in dogs
Experimental Gerontology, 2014Co-Authors: Koichiro Iohara, Masashi Murakami, Kazuhiko Nakata, Misako NakashimaAbstract:The age-associated decline in the regenerative abilities of mesenchymal stem cells (MSCs) may be due to age-related changes in reduction in number, intrinsic properties of MSCs and extrinsic factors of the extracellular environment (the stem cell niche). The effect of age on the efficacy of MSC transplantation on Regeneration, however, has not been clearly demonstrated due to variable methods of isolation of MSCs and variations in stem cell populations. In this study, dental Pulp stem cell (DPSC) subsets were isolated from young and aged dog teeth based on their migratory response to granulocyte-colony stimulating factor (G-CSF) (MDPSCs). In order to study the age-associated changes, their biological properties and stability were compared and the regenerative potential was examined in a Pulpectomized tooth model in aged dogs. MDPSCs from aged dogs were efficiently enriched in stem cells, expressing trophic factors with high proliferation, migration and anti-apoptotic effects as in MDPSCs from young dogs. However, Pulp Regeneration was retarded 120 days after autologous transplantation of aged MDPSCs. We further demonstrated that isolated periodontal ligament stem cells (PDLSCs) from aged dogs, representative of migrating stem cells from outside of the tooth compartment to regenerate Pulp tissue, had lower proliferation, migration and anti-apoptotic abilities. These results therefore provide a better understanding of the mechanisms involved in the age-dependent decline in Pulp Regeneration, which are attributed to a decrease in the regenerative potential of resident stem cells.
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A Novel Combinatorial Therapy With Pulp Stem Cells and Granulocyte Colony-Stimulating Factor for Total Pulp Regeneration
Stem cells translational medicine, 2013Co-Authors: Koichiro Iohara, Masashi Murakami, Yohei Osako, Norio Takeuchi, Masataka Ito, Ryo Ishizaka, Shinji Utunomiya, Hiroshi Nakamura, Kenji Matsushita, Misako NakashimaAbstract:Treatment of deep caries with Pulpitis is a major challenge in dentistry. Stem cell therapy represents a potential strategy to regenerate the dentin-Pulp complex, enabling conservation and restoration of teeth. The objective of this study was to assess the efficacy and safety of Pulp stem cell transplantation as a prelude for the impending clinical trials. Clinical-grade Pulp stem cells were isolated and expanded according to good manufacturing practice conditions. The absence of contamination, abnormalities/aberrations in karyotype, and tumor formation after transplantation in an immunodeficient mouse ensured excellent quality control. After autologous transplantation of Pulp stem cells with granulocyte-colony stimulating factor (G-CSF) in a dog Pulpectomized tooth, regenerated Pulp tissue including vasculature and innervation completely filled in the root canal, and regenerated dentin was formed in the coronal part and prevented microleakage up to day 180. Transplantation of Pulp stem cells with G-CSF yielded a significantly larger amount of regenerated dentin-Pulp complex compared with transplantation of G-CSF or stem cells alone. Also noteworthy was the reduction in the number of inflammatory cells and apoptotic cells and the significant increase in neurite outgrowth compared with results without G-CSF. The transplanted stem cells expressed angiogenic/neurotrophic factors. It is significant that G-CSF together with conditioned medium of Pulp stem cells stimulated cell migration and neurite outgrowth, prevented cell death, and promoted immunosuppression in vitro. Furthermore, there was no evidence of toxicity or adverse events. In conclusion, the combinatorial trophic effects of Pulp stem cells and G-CSF are of immediate utility for Pulp/dentin Regeneration, demonstrating the prerequisites of safety and efficacy critical for clinical applications.
Imad About - One of the best experts on this subject based on the ideXlab platform.
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Pulp capping materials modulate the balance between inflammation and Regeneration
Dental Materials, 2019Co-Authors: Thomas Giraud, Charlotte Jeanneau, Patrick Laurent, Hengameh Bakhtiar, Charlotte Rombouts, Imad AboutAbstract:The interrelations between inflammation and Regeneration are of particular significance within the dental Pulp tissue inextensible environment. Recent data have demonstrated the Pulp capacity to respond to insults by initiating an inflammatory reaction and dentin Pulp Regeneration. Different study models have been developed in vitro and in vivo to investigate the initial steps of Pulp inflammation and Regeneration. These include endothelial cell interaction with inflammatory cells, stem cell interaction with Pulp fibroblasts, migration chambers to study cell recruitment and entire human tooth culture model. Using these models, the Pulp has been shown to possess an inherent anti-inflammatory potential and a high Regeneration capacity in all teeth and at all ages. The same models were used to investigate the effects of tricalcium silicate-based Pulp capping materials, which were found to modulate the Pulp anti-inflammatory potential and Regeneration capacity. Among these, resin-containing materials such as TheraCal ® shift the Pulp response towards the inflamma-tory reaction while altering the Regeneration process. On the opposite, resin-free materials such as Biodentine TM have an anti-inflammatory potential and induce the Pulp Regeneration capacity. This knowledge contradicts the new tendency of developing resin-based calcium silicate hybrid materials for direct Pulp capping. Additionally, it would allow investigating the modulatory effects of newly released Pulp capping materials on the balance between tissue inflammation and Regeneration. It would also set the basis for developing future capping materials targeting these processes.
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Potential Therapeutic Strategy of Targeting Pulp Fibroblasts in Dentin-Pulp Regeneration.
Journal of endodontics, 2017Co-Authors: Charlotte Jeanneau, Fionnuala T Lundy, Ikhlas A El Karim, Imad AboutAbstract:Fibroblasts represent the most abundant population within the dental Pulp. Although other cell types such as odontoblasts and stem cells have been extensively investigated, very little attention was given to the fibroblasts, which have major roles in regulating the Pulp biology and function under normal and pathologic conditions. Indeed, although Pulp fibroblasts control the Pulp vascularization and innervation under physiological conditions, these cells synthesize growth factors that enhance dentin-Pulp Regeneration, vascularization, and innervation. Pulp fibroblasts also represent a unique cell population because they are the only non-hepatic and non-immune cell type capable of synthesizing all complement proteins leading to production of biologically active fragments such as C3a, C5a, and membrane attack complex, which play major roles in the Pulp Regeneration processes. C3a fragment is involved in inducing the proliferation of both stem cells and Pulp fibroblasts. It is also involved in stem cell mobilization and Pulp fibroblast recruitment. C5a guides nerve sprouting and stem cell recruitment. The membrane attack complex fixes on cariogenic bacteria walls, leading to their direct destruction. These data demonstrate the central role played by Pulp fibroblasts in regulating the dentin-Pulp tissue by directly destroying cariogenic bacteria and by releasing bioactive fragments involved in nerve sprouting and stem cell recruitment and Pulp Regeneration. Taken together, this shows that targeting Pulp fibroblasts represents a realistic strategy to induce complete dentin-Pulp Regeneration.
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Pulp fibroblasts synthesize functional complement proteins involved in initiating dentin Pulp Regeneration
American Journal of Pathology, 2014Co-Authors: F Chmilewsky, Charlotte Jeanneau, Patrick Laurent, Imad AboutAbstract:The complement system is an efficient plasma immune surveillance system that controls tissue injury and infection. Although the liver constitutes the primary circulating complement protein synthesis site, extrahepatic synthesis is known to optimize local tissue inflammatory reaction. Because dentin–Pulp Regeneration is known to be regulated locally, we investigated activation of the local complement system within the dental Pulp and its role in initiating the Regeneration process. Membrane attack complex (C5b-9) formation and Gram's staining revealed that complement activation is correlated with the presence of Gram-positive bacteria in carious human teeth. RT-PCR analysis demonstrated that cultured human Pulp fibroblasts stimulated with lipoteichoic acid produce all the proteins required for efficient complement activation. This was demonstrated in vitro by C5b-9 formation and C5a active fragment production in the absence of plasma proteins. Finally, the dynamic migration assays performed in μ-Slide chemotaxis chambers and use of a C5aR-specific antagonist (W54011) demonstrated that the activation of complement proteins synthesized by Pulp fibroblasts and the subsequent release of C5a specifically induced Pulp progenitor cell recruitment. Our study reveals human Pulp fibroblasts as the first nonimmune cell type capable of synthesizing all complement proteins. These fibroblasts cells contribute significantly to tissue Regeneration by recruiting Pulp progenitors via complement activation, which suggests to a potential therapeutic strategy of targeting Pulp fibroblasts in dentin–Pulp Regeneration.
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sources of dentin Pulp Regeneration signals and their modulation by the local microenvironment
Journal of Endodontics, 2014Co-Authors: Fanny Chmilewsky, Charlotte Jeanneau, Jacques Dejou, Imad AboutAbstract:Many aspects of dentin Pulp tissue Regeneration have been investigated, and it has been shown that dentin Pulp has a high Regeneration capacity. This seems to be because of the presence of progenitor cells and inductive Regeneration signals from different origins. These signals can be liberated after the acidic dissolution of carious dentin as well as from Pulp fibroblasts and endothelial cells in cases of traumatic injury. Thus, both carious lesions and Pulp cells provide the required mediators for complete dentin-Pulp Regeneration including reparative dentin secretion, angiogenesis, and innervation. Additionally, all dentin Pulp insults including carious "infection," traumatic injuries, application of restorative materials on the injured dentin Pulp, and subsequent apoptosis are known activators of the complement system. This activation leads to the production of several biologically active fragments responsible for the vascular modifications and the attraction of immune cells to the inflammatory/injury site. Among these, C5a is involved in the recruitment of Pulp progenitor cells, which express the C5a receptor. Thus, in addition to dentin and Pulp cells, plasma should be considered as an additional source of Regeneration signals.
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dentin Pulp Regeneration the primordial role of the microenvironment and its modification by traumatic injuries and bioactive materials
Endodontic Topics, 2013Co-Authors: Imad AboutAbstract:Understanding dentinogenesis and Pulp Regeneration during physiological and pathological conditions represents a real challenge in the provision of a suitable treatment that ideally leads to the induction of the Pulp regenerative potential. This paper focusses on the early steps of dentin–Pulp Regeneration that appear to be critical after Pulp capping procedures. Different models are described in this paper where the interactions between different cell types in vitro illustrate their role in maintaining Pulpal homeostasis. After traumatic injuries, the cells modify the local Pulpal microenvironment by secreting growth factors that orchestrate and induce the processes required for dentin–Pulp Regeneration. Applying dental materials onto the injured Pulp modifies this local microenvironment and affects the potential for Pulpal Regeneration. The paper also describes the added value of developing an entire human tooth culture model for understanding these early steps and discusses the interest of its use in evaluating newly developed Pulp capping materials through the example of BiodentineTM, developed as a dentin substitute. The growth factors sustained release simulating the local microenvironment is also discussed. Simulating the Pulp local environment with a continuous growth factors release is also a basic requirement for establishing future Pulp tissue engineering.
