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Hiroaki Nakamura - One of the best experts on this subject based on the ideXlab platform.
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evaluation of dual release of stromal cell derived factor 1 and basic fibroblast growth factor with Nerve Conduit for peripheral Nerve regeneration an experimental study in mice
2020Co-Authors: Kosuke Shintani, Takuya Uemura, Kiyohito Takamatsu, Mitsuhiro Okada, Takuya Yokoi, Ema Onode, Yasuhiko Tabata, Hiroaki NakamuraAbstract:Background The development of drug delivery systems has enabled the release of multiple bioactive molecules. The efficacy of Nerve Conduits coated with dual controlled release of stromal cell-derived factor-1 (SDF-1) and basic fibroblast growth factor (bFGF) for peripheral Nerve regeneration was investigated. Materials and methods Sixty-two C57BL6 mice were used for peripheral Nerve regeneration with a Nerve Conduit (inner diameter, 1 mm, and length, 7 mm) and an autograft. The mice were randomized into five groups based on the different repairs of Nerve defects. In the group of repair with Conduits alone (n = 9), a 5-mm sciatic Nerve defect was repaired by the Nerve Conduit. In the group of repair with Conduits coated with bFGF (n = 10), SDF-1 (n = 10), and SDF-1/bFGF (n = 10), it was repaired by the Nerve Conduit with bFGF gelatin, SDF-1 gelatin, and SDF-1/bFGF gelatin, respectively. In the group of repair with autografts (n = 10), it was repaired by the resected Nerve itself. The functional recovery, Nerve regeneration, angiogenesis, and TGF-β1 gene expression were assessed. Results In the Conduits coated with SDF-1/bFGF group, the mean sciatic functional index value (-88.68 ± 10.64, p = .034) and the axon number (218.8 ± 111.1, p = .049) were significantly higher than the Conduit alone group, followed by the autograft group; in addition, numerous CD34-positive cells and micro vessels were observed. TGF-β1 gene expression relative values in the Conduits with SDF-1/bFGF group at 3 days (7.99 ± 5.14, p = .049) significantly increased more than the Conduits alone group. Conclusion Nerve Conduits coated with dual controlled release of SDF-1 and bFGF promoted peripheral Nerve regeneration.
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long term efficacy and safety outcomes of transplantation of induced pluripotent stem cell derived neurospheres with bioabsorbable Nerve Conduits for peripheral Nerve regeneration in mice
2015Co-Authors: Takuya Uemura, Kiyohito Takamatsu, Mikinori Ikeda, Mitsuhiro Okada, Takuya Yokoi, Hiroaki NakamuraAbstract:The induced pluripotent stem cell (iPSc) offers great potential for cell-based therapy in regenerative medicine. We previously developed tissue-engineered bioabsorbable Nerve Conduits coated with iPSc-derived neurospheres for use in peripheral Nerve repair. Here, we examine the long-term efficacy and safety of using Nerve Conduits with iPSc technology for peripheral Nerve repair in mice. The Nerve Conduit consisted of an outer layer of a poly L-lactide mesh and an inner layer of porous sponge composed of 50% L-lactide and 50% e-caprolactone. Secondary neurospheres were derived from mouse iPScs, resuspended and cultured within the Conduit for 14 days. Conduits were implanted within surgically administered 5-mm defects in the left sciatic Nerve of mice (iPSc group; n = 14). The defects in the control group (n = 13) were reconstructed using the Nerve Conduit alone. At 4, 8, 12, 24 and 48 weeks postsurgery, motor and sensory functional recovery in the iPSc group had improved significantly more than in the control group. At 24 and 48 weeks, histological analysis revealed axonal regeneration in the Nerve Conduits of both groups. However, axonal regeneration and myelination were significantly enhanced in the iPSc group. No teratomas were identified in the iPSc group at any time point. Therefore, we here demonstrate that bioabsorbable Nerve Conduits coated with iPSc-derived neurospheres promote enhanced regeneration of peripheral Nerves and functional recovery without teratoma formation in the long term. This combination of iPSc technology and bioabsorbable Nerve Conduits has the potential to be a safe future tool for the treatment of peripheral Nerve defects.
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acceleration of peripheral Nerve regeneration using Nerve Conduits in combination with induced pluripotent stem cell technology and a basic fibroblast growth factor drug delivery system
2014Co-Authors: Mikinori Ikeda, Takuya Uemura, Kiyohito Takamatsu, Mitsuhiro Okada, Kenichi Kazuki, Yoshito Ikada, Yasuhiko Tabata, Hiroaki NakamuraAbstract:Various modifications including addition of Schwann cells or incorporation of growth factors with bioabsorbable Nerve Conduits have been explored as options for peripheral Nerve repair. However, no reports of Nerve Conduits containing both supportive cells and growth factors have been published as a regenerative therapy for peripheral Nerves. In the present study, sciatic Nerve gaps in mice were reconstructed in the following groups: Nerve Conduit alone (control group), Nerve Conduit coated with induced pluripotent stem cell (iPSc)-derived neurospheres (iPSc group), Nerve Conduit coated with iPSc-derived neurospheres and basic fibroblast growth factor (bFGF)-incorporated gelatin microspheres (iPSc + bFGF group), and autograft. The fastest functional recovery and the greatest axon regeneration occurred in the autograft group, followed in order by the iPSc + bFGF group, iPSc group, and control group until 12 weeks after reconstruction. Thus, peripheral Nerve regeneration using Nerve Conduits and functional recovery in mice was accelerated by a combination of iPSc-derived neurospheres and a bFGF drug delivery system. The combination of all three fundamental methodologies, iPSc technology for supportive cells, bioabsorbable Nerve Conduits for scaffolds, and a bFGF drug delivery system for growth factors, was essential for peripheral Nerve regenerative therapy.
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a tissue engineered bioabsorbable Nerve Conduit created by three dimensional culture of induced pluripotent stem cell derived neurospheres
2011Co-Authors: Takuya Uemura, Kiyohito Takamatsu, Mikinori Ikeda, Mitsuhiro Okada, Kenichi Kazuki, Yoshito Ikada, Hiroaki NakamuraAbstract:We previously reported a bioabsorbable Nerve Conduit coated with Schwann cells for the treatment of peripheral Nerve defects. Since there have been dramatic developments in induced pluripotent stem (iPS) cells in recent years, the purpose of the present study was to create a tissue-engineered Nerve Conduit coated with iPS cell-derived neurospheres. Such a Conduit was constructed by three-dimensional (3D)-culture of these cells using a bioabsorbable polymer Conduit as a scaffold. The Nerve Conduit was composed of a mesh of poly L-lactide, and a porous sponge of 50% poly L-lactide and 50% poly e-caprolactone. The primary and secondary neurospheres (PNS and SNS, respectively) induced from iPS cells were suspended in individual Conduits. The Conduits were incubated for 7 or 14 days in vitro and then evaluated using immunohistochemistry. All of the 7- and 14-day differentiated PNS and SNS were observed to have adhered to the inner surface of the Conduits and to have migrated into the inner porous sponge. The engrafted cells were positive for anti-Tuj1, -S-100 and -GFAP antibodies, indicating that their pluripotent ability to form neural or glial cells was maintained. These findings indicate the feasibility of creating Nerve Conduits coated with a 3D-culture of iPS cell-derived neurospheres for the treatment of peripheral Nerve defects.
Takuya Uemura - One of the best experts on this subject based on the ideXlab platform.
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evaluation of dual release of stromal cell derived factor 1 and basic fibroblast growth factor with Nerve Conduit for peripheral Nerve regeneration an experimental study in mice
2020Co-Authors: Kosuke Shintani, Takuya Uemura, Kiyohito Takamatsu, Mitsuhiro Okada, Takuya Yokoi, Ema Onode, Yasuhiko Tabata, Hiroaki NakamuraAbstract:Background The development of drug delivery systems has enabled the release of multiple bioactive molecules. The efficacy of Nerve Conduits coated with dual controlled release of stromal cell-derived factor-1 (SDF-1) and basic fibroblast growth factor (bFGF) for peripheral Nerve regeneration was investigated. Materials and methods Sixty-two C57BL6 mice were used for peripheral Nerve regeneration with a Nerve Conduit (inner diameter, 1 mm, and length, 7 mm) and an autograft. The mice were randomized into five groups based on the different repairs of Nerve defects. In the group of repair with Conduits alone (n = 9), a 5-mm sciatic Nerve defect was repaired by the Nerve Conduit. In the group of repair with Conduits coated with bFGF (n = 10), SDF-1 (n = 10), and SDF-1/bFGF (n = 10), it was repaired by the Nerve Conduit with bFGF gelatin, SDF-1 gelatin, and SDF-1/bFGF gelatin, respectively. In the group of repair with autografts (n = 10), it was repaired by the resected Nerve itself. The functional recovery, Nerve regeneration, angiogenesis, and TGF-β1 gene expression were assessed. Results In the Conduits coated with SDF-1/bFGF group, the mean sciatic functional index value (-88.68 ± 10.64, p = .034) and the axon number (218.8 ± 111.1, p = .049) were significantly higher than the Conduit alone group, followed by the autograft group; in addition, numerous CD34-positive cells and micro vessels were observed. TGF-β1 gene expression relative values in the Conduits with SDF-1/bFGF group at 3 days (7.99 ± 5.14, p = .049) significantly increased more than the Conduits alone group. Conclusion Nerve Conduits coated with dual controlled release of SDF-1 and bFGF promoted peripheral Nerve regeneration.
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long term efficacy and safety outcomes of transplantation of induced pluripotent stem cell derived neurospheres with bioabsorbable Nerve Conduits for peripheral Nerve regeneration in mice
2015Co-Authors: Takuya Uemura, Kiyohito Takamatsu, Mikinori Ikeda, Mitsuhiro Okada, Takuya Yokoi, Hiroaki NakamuraAbstract:The induced pluripotent stem cell (iPSc) offers great potential for cell-based therapy in regenerative medicine. We previously developed tissue-engineered bioabsorbable Nerve Conduits coated with iPSc-derived neurospheres for use in peripheral Nerve repair. Here, we examine the long-term efficacy and safety of using Nerve Conduits with iPSc technology for peripheral Nerve repair in mice. The Nerve Conduit consisted of an outer layer of a poly L-lactide mesh and an inner layer of porous sponge composed of 50% L-lactide and 50% e-caprolactone. Secondary neurospheres were derived from mouse iPScs, resuspended and cultured within the Conduit for 14 days. Conduits were implanted within surgically administered 5-mm defects in the left sciatic Nerve of mice (iPSc group; n = 14). The defects in the control group (n = 13) were reconstructed using the Nerve Conduit alone. At 4, 8, 12, 24 and 48 weeks postsurgery, motor and sensory functional recovery in the iPSc group had improved significantly more than in the control group. At 24 and 48 weeks, histological analysis revealed axonal regeneration in the Nerve Conduits of both groups. However, axonal regeneration and myelination were significantly enhanced in the iPSc group. No teratomas were identified in the iPSc group at any time point. Therefore, we here demonstrate that bioabsorbable Nerve Conduits coated with iPSc-derived neurospheres promote enhanced regeneration of peripheral Nerves and functional recovery without teratoma formation in the long term. This combination of iPSc technology and bioabsorbable Nerve Conduits has the potential to be a safe future tool for the treatment of peripheral Nerve defects.
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acceleration of peripheral Nerve regeneration using Nerve Conduits in combination with induced pluripotent stem cell technology and a basic fibroblast growth factor drug delivery system
2014Co-Authors: Mikinori Ikeda, Takuya Uemura, Kiyohito Takamatsu, Mitsuhiro Okada, Kenichi Kazuki, Yoshito Ikada, Yasuhiko Tabata, Hiroaki NakamuraAbstract:Various modifications including addition of Schwann cells or incorporation of growth factors with bioabsorbable Nerve Conduits have been explored as options for peripheral Nerve repair. However, no reports of Nerve Conduits containing both supportive cells and growth factors have been published as a regenerative therapy for peripheral Nerves. In the present study, sciatic Nerve gaps in mice were reconstructed in the following groups: Nerve Conduit alone (control group), Nerve Conduit coated with induced pluripotent stem cell (iPSc)-derived neurospheres (iPSc group), Nerve Conduit coated with iPSc-derived neurospheres and basic fibroblast growth factor (bFGF)-incorporated gelatin microspheres (iPSc + bFGF group), and autograft. The fastest functional recovery and the greatest axon regeneration occurred in the autograft group, followed in order by the iPSc + bFGF group, iPSc group, and control group until 12 weeks after reconstruction. Thus, peripheral Nerve regeneration using Nerve Conduits and functional recovery in mice was accelerated by a combination of iPSc-derived neurospheres and a bFGF drug delivery system. The combination of all three fundamental methodologies, iPSc technology for supportive cells, bioabsorbable Nerve Conduits for scaffolds, and a bFGF drug delivery system for growth factors, was essential for peripheral Nerve regenerative therapy.
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a tissue engineered bioabsorbable Nerve Conduit created by three dimensional culture of induced pluripotent stem cell derived neurospheres
2011Co-Authors: Takuya Uemura, Kiyohito Takamatsu, Mikinori Ikeda, Mitsuhiro Okada, Kenichi Kazuki, Yoshito Ikada, Hiroaki NakamuraAbstract:We previously reported a bioabsorbable Nerve Conduit coated with Schwann cells for the treatment of peripheral Nerve defects. Since there have been dramatic developments in induced pluripotent stem (iPS) cells in recent years, the purpose of the present study was to create a tissue-engineered Nerve Conduit coated with iPS cell-derived neurospheres. Such a Conduit was constructed by three-dimensional (3D)-culture of these cells using a bioabsorbable polymer Conduit as a scaffold. The Nerve Conduit was composed of a mesh of poly L-lactide, and a porous sponge of 50% poly L-lactide and 50% poly e-caprolactone. The primary and secondary neurospheres (PNS and SNS, respectively) induced from iPS cells were suspended in individual Conduits. The Conduits were incubated for 7 or 14 days in vitro and then evaluated using immunohistochemistry. All of the 7- and 14-day differentiated PNS and SNS were observed to have adhered to the inner surface of the Conduits and to have migrated into the inner porous sponge. The engrafted cells were positive for anti-Tuj1, -S-100 and -GFAP antibodies, indicating that their pluripotent ability to form neural or glial cells was maintained. These findings indicate the feasibility of creating Nerve Conduits coated with a 3D-culture of iPS cell-derived neurospheres for the treatment of peripheral Nerve defects.
Yasuhiko Shimizu - One of the best experts on this subject based on the ideXlab platform.
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recurrent laryngeal Nerve regeneration by tissue engineering
2003Co-Authors: Shinichi Kanemaru, Tatsuo Nakamura, Koichi Omori, Hisayoshi Kojima, Akhmar Magrufov, Yasuyuki Hiratsuka, Yasuhiko ShimizuAbstract:The recurrent laryngeal Nerve (RLN) does not regenerate well after it has been cut, and no current surgical methods achieve functional regeneration. Here, we evaluate the functional regeneration of the RLN after reconstruction using a biodegradable Nerve Conduit or an autologous Nerve graft. The Nerve Conduit was made of a polyglycolic acid (PGA) tube coated with collagen. A 10-mm gap in the resected Nerve was bridged by a PGA tube in 6 adult beagle dogs (group 1) and by an autologous Nerve graft in 3 dogs (group 2). Fiberscopic observation revealed functional regeneration of the RLN in 4 of the 6 dogs in group 1. No regeneration of the RLN was observed in any dog in group 2. We also tested for axonal transport, and measured the compound muscle action potential. The RLN can be functionally regenerated with a PGA tube, which may act as a scaffold for the growth of regenerating axons.
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evaluation of peripheral Nerve regeneration across an 80 mm gap using a polyglycolic acid pga collagen Nerve Conduit filled with laminin soaked collagen sponge in dogs
2002Co-Authors: Toshinari Toba, Tatsuo Nakamura, A K Lynn, Kazuya Matsumoto, Seijun Fukuda, Makoto Yoshitani, Yoshio Hori, Yasuhiko ShimizuAbstract:Abstract We evaluated peripheral Nerve regeneration using a novel artificial Nerve Conduit. The Conduit was made of a polyglycolic acid(PGA) - collagen tube filled with laminin- soaked collagen sponge. We implanted this Nerve Conduit across an 80mm gap in the peroneal Nerve of dogs. Histological observation 12 months after implantation showed numerous unmyelinated and myelinated Nerve fibershad regenerated beyond the gap. Neurofilaments were widely observed immunohistochemically in the regenerated Nerve segments. These findings indicated that newly regenerated axons had extended across the gap and connected into the distal Nerve segments. Compound muscle action potentials(CMAPs) and somatosensory evoked potentials (SEPs) were recorded in all dogs. At 12 months, the CMAPs indicated complete recovery, while the SEPs showed incomplete but substantial recovery. Walking patterns had returned to near-normal 12 months after implantation. Use of this Nerve Conduit can lead to peripheral Nerve elongation and favorable functional recovery across a wider Nerve gap.
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regeneration of canine peroneal Nerve with the use of a polyglycolic acid collagen tube filled with laminin soaked collagen sponge a comparative study of collagen sponge and collagen fibers as filling materials for Nerve Conduits
2001Co-Authors: Toshinari Toba, Tatsuo Nakamura, Kazuya Matsumoto, Seijun Fukuda, Makoto Yoshitani, Yoshio Hori, Yasuhiko Shimizu, Katsunori Ohnishi, Hiroki Ueda, Katsuaki EndoAbstract:A novel artificial Nerve Conduit was developed and its efficiency was evaluated on the basis of promotion of peripheral Nerve regeneration across an 80-mm gap in dogs. The Nerve Conduit was made of a polyglycolic acid–collagen tube filled with laminin-soaked collagen sponge. Conduits filled with either sponge- or fiber-form collagen were implanted into an 80-mm gap of the peroneal Nerve (five dogs for each form). Twelve months postoperatively Nerve regeneration was superior in the sponge group both morphometrically (percentage of neural tissue: fiber: 39.7 ± 5.2, sponge: 43.0 ± 4.5, n=3) and electrophysiologically (fiber: CMAP 1.06 ± 0.077, SEP 1.32 ± 0.127 sponge: CMAP 1.04 ± 0.106, SEP 1.24 ± 0.197, n=5), although these differences were not statistically significant. The observed regeneration was complementary to successful results reported previously in the same model, in which collagen fibers exclusively were used. The results indicate a possible superiority of collagen sponge over collagen fibers as filling materials. In addition, the mass-producibility, superior scaffolding potential, and capacity for gradual release of soluble factors of the sponge provide make it an attractive alternative to fine fibers, which are both technologically difficult and costly to produce. This newly developed Nerve Conduit has the potential to enhance peripheral Nerve regeneration across longer gaps commonly encountered in clinical settings. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 622–630, 2001
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peripheral Nerve regeneration across an 80 mm gap bridged by a polyglycolic acid pga collagen tube filled with laminin coated collagen fibers a histological and electrophysiological evaluation of regenerated Nerves
2000Co-Authors: Kazuya Matsumoto, Tatsuo Nakamura, Katsunori Ohnishi, Tetsuya Kiyotani, Takashi Sekine, Hiroki Ueda, Katsuaki Endo, Yasuhiko ShimizuAbstract:Abstract We evaluated peripheral Nerve regeneration across an 80-mm gap using a novel artificial Nerve Conduit. The Conduit was made of a polyglycolic acid (PGA)–collagen tube filled with laminin-coated collagen fibers. Twelve beagle dogs underwent implantation of the Nerve Conduit across an 80-mm gap in the left peroneal Nerve. In four other dogs used as negative controls, the Nerve was resected and left unconnected. Histological observation showed that numerous unmyelinated and myelinated Nerve fibers, all smaller in diameter and with a thinner myelin sheath than normal Nerve fibers, regrew through and beyond the gap 12 months after implantation. The distribution of the regenerated axonal diameters was different from that of the normal axonal diameters. Compound muscle action potentials, motor evoked potentials, and somatosensory evoked potentials were recorded in most animals 3 months after implantation. Peak amplitudes and latencies recovered gradually, which indicating the functional establishment of the Nerve connection with the target organs. In addition to the ordinary electrophysiological recoveries, potentials with distinct latencies originating from Aα, Aδ and C fibers became distinguishable at the 6th lumbar vertebra following stimulation of the peroneal Nerve distal to the gap 12 months after implantation. The pattern of walking without load was restored to almost normal 10–12 months after implantation. Neither electrophysiological nor histological restoration was obtained in the controls. Our Nerve Conduit can guide peripheral Nerve elongation and lead to favorable functional recovery across a wider Nerve gap than previously reported artificial Nerve Conduits.
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peripheral Nerve regeneration across an 80 mm gap bridged by a polyglycolic acid pga collagen tube filled with laminin coated collagen fibers a histological and electrophysiological evaluation of regenerated Nerves
2000Co-Authors: Kazuya Matsumoto, Tatsuo Nakamura, Katsunori Ohnishi, Tetsuya Kiyotani, Takashi Sekine, Hiroki Ueda, Katsuaki Endo, Yasuhiko ShimizuAbstract:We evaluated peripheral Nerve regeneration across an 80-mm gap using a novel artificial Nerve Conduit. The Conduit was made of a polyglycolic acid (PGA)-collagen tube filled with laminin-coated collagen fibers. Twelve beagle dogs underwent implantation of the Nerve Conduit across an 80-mm gap in the left peroneal Nerve. In four other dogs used as negative controls, the Nerve was resected and left unconnected. Histological observation showed that numerous unmyelinated and myelinated Nerve fibers, all smaller in diameter and with a thinner myelin sheath than normal Nerve fibers, regrew through and beyond the gap 12 months after implantation. The distribution of the regenerated axonal diameters was different from that of the normal axonal diameters. Compound muscle action potentials, motor evoked potentials, and somatosensory evoked potentials were recorded in most animals 3 months after implantation. Peak amplitudes and latencies recovered gradually, which indicating the functional establishment of the Nerve connection with the target organs. In addition to the ordinary electrophysiological recoveries, potentials with distinct latencies originating from Aalpha, Adelta and C fibers became distinguishable at the 6th lumbar vertebra following stimulation of the peroneal Nerve distal to the gap 12 months after implantation. The pattern of walking without load was restored to almost normal 10-12 months after implantation. Neither electrophysiological nor histological restoration was obtained in the controls. Our Nerve Conduit can guide peripheral Nerve elongation and lead to favorable functional recovery across a wider Nerve gap than previously reported artificial Nerve Conduits.
Tatsuo Nakamura - One of the best experts on this subject based on the ideXlab platform.
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Can Nerve regeneration on an artificial Nerve Conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?
2017Co-Authors: Yoshiki Shionoya, Katsuhisa Sunada, Keiji Shigeno, Akira Nakada, Michitaka Honda, Tatsuo NakamuraAbstract:This study aimed to determine whether Nerve regeneration by means of an artificial Nerve Conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB) in a canine model. This study involved two experiments—in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar Nerve (IAN) repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory Nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes) after Nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved Nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow.
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Regeneration of the Nerves in the Aerial Cavity with an Artificial Nerve Conduit-Reconstruction of Chorda Tympani Nerve Gaps-
2016Co-Authors: Toshiaki Yamanaka, Hiroshi Hosoi, Takayuki Murai, Takehiko Kobayashi, Yuji Inada, Tatsuo NakamuraAbstract:Objectives/Hypothesis: Due to its anatomical features, the chorda tympani Nerve (CTN) is sometimes sacrificed during middle ear surgery, resulting in taste dysfunction. We examined the effect of placing an artificial Nerve Conduit, a polyglycolic acid (PGA)-collagen tube, across the gap in the section of the resected chorda tympani Nerve (CTN) running through the tympanic cavity. Methods: The CTN was reconstructed with a PGA-collagen tube in three patients with taste disturbance who underwent CTN resection. To evaluate the effect of the reconstruction procedure on the patients ’ gustatory function, we measured the patients ’ electrogustometry (EGM) thresholds. The patients were followed-up for at least two years. Results: Gustatory function was completely restored in all of the patients after the reconstruction. The patients ’ EGM thresholds exhibited early improvements within one to two weeks and had returned to their normal ranges within three months. They subsequently remained stable throughout the two-year follow-up period. In a patient who underwent a second surgical procedure, it was found that the PGA-collagen tube used in the first surgical procedure had been absorbed and replaced by new CTN fibers with blood vessels on their surfaces. Conclusion: These results suggest that reconstruction of the CTN with an artificial Nerve Conduit, a PGA-collagen tube, allows functional and morphological regeneration of the Nerve and facilitates the recovery of taste function. PGA-collage
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peripheral Nerve regeneration by tissue engineering for prevention of misdirection
2015Co-Authors: Shinichi Kanemaru, Tatsuo NakamuraAbstract:We created an artificial Nerve Conduit called a “polyglycolic acid tube” based on a basic concept of in situ tissue engineering to achieve complete functional regeneration without misdirected reinnervation. We successfully achieved functional regeneration of the recurrent laryngeal Nerve in dogs using this artificial Nerve Conduit. Based on our results, we began its use in human clinical application to regenerate peripheral Nerves (such as the recurrent laryngeal Nerve, facial Nerve, and chorda tympani Nerve).
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recurrent laryngeal Nerve regeneration by tissue engineering
2003Co-Authors: Shinichi Kanemaru, Tatsuo Nakamura, Koichi Omori, Hisayoshi Kojima, Akhmar Magrufov, Yasuyuki Hiratsuka, Yasuhiko ShimizuAbstract:The recurrent laryngeal Nerve (RLN) does not regenerate well after it has been cut, and no current surgical methods achieve functional regeneration. Here, we evaluate the functional regeneration of the RLN after reconstruction using a biodegradable Nerve Conduit or an autologous Nerve graft. The Nerve Conduit was made of a polyglycolic acid (PGA) tube coated with collagen. A 10-mm gap in the resected Nerve was bridged by a PGA tube in 6 adult beagle dogs (group 1) and by an autologous Nerve graft in 3 dogs (group 2). Fiberscopic observation revealed functional regeneration of the RLN in 4 of the 6 dogs in group 1. No regeneration of the RLN was observed in any dog in group 2. We also tested for axonal transport, and measured the compound muscle action potential. The RLN can be functionally regenerated with a PGA tube, which may act as a scaffold for the growth of regenerating axons.
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evaluation of peripheral Nerve regeneration across an 80 mm gap using a polyglycolic acid pga collagen Nerve Conduit filled with laminin soaked collagen sponge in dogs
2002Co-Authors: Toshinari Toba, Tatsuo Nakamura, A K Lynn, Kazuya Matsumoto, Seijun Fukuda, Makoto Yoshitani, Yoshio Hori, Yasuhiko ShimizuAbstract:Abstract We evaluated peripheral Nerve regeneration using a novel artificial Nerve Conduit. The Conduit was made of a polyglycolic acid(PGA) - collagen tube filled with laminin- soaked collagen sponge. We implanted this Nerve Conduit across an 80mm gap in the peroneal Nerve of dogs. Histological observation 12 months after implantation showed numerous unmyelinated and myelinated Nerve fibershad regenerated beyond the gap. Neurofilaments were widely observed immunohistochemically in the regenerated Nerve segments. These findings indicated that newly regenerated axons had extended across the gap and connected into the distal Nerve segments. Compound muscle action potentials(CMAPs) and somatosensory evoked potentials (SEPs) were recorded in all dogs. At 12 months, the CMAPs indicated complete recovery, while the SEPs showed incomplete but substantial recovery. Walking patterns had returned to near-normal 12 months after implantation. Use of this Nerve Conduit can lead to peripheral Nerve elongation and favorable functional recovery across a wider Nerve gap.
Kiyohito Takamatsu - One of the best experts on this subject based on the ideXlab platform.
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evaluation of dual release of stromal cell derived factor 1 and basic fibroblast growth factor with Nerve Conduit for peripheral Nerve regeneration an experimental study in mice
2020Co-Authors: Kosuke Shintani, Takuya Uemura, Kiyohito Takamatsu, Mitsuhiro Okada, Takuya Yokoi, Ema Onode, Yasuhiko Tabata, Hiroaki NakamuraAbstract:Background The development of drug delivery systems has enabled the release of multiple bioactive molecules. The efficacy of Nerve Conduits coated with dual controlled release of stromal cell-derived factor-1 (SDF-1) and basic fibroblast growth factor (bFGF) for peripheral Nerve regeneration was investigated. Materials and methods Sixty-two C57BL6 mice were used for peripheral Nerve regeneration with a Nerve Conduit (inner diameter, 1 mm, and length, 7 mm) and an autograft. The mice were randomized into five groups based on the different repairs of Nerve defects. In the group of repair with Conduits alone (n = 9), a 5-mm sciatic Nerve defect was repaired by the Nerve Conduit. In the group of repair with Conduits coated with bFGF (n = 10), SDF-1 (n = 10), and SDF-1/bFGF (n = 10), it was repaired by the Nerve Conduit with bFGF gelatin, SDF-1 gelatin, and SDF-1/bFGF gelatin, respectively. In the group of repair with autografts (n = 10), it was repaired by the resected Nerve itself. The functional recovery, Nerve regeneration, angiogenesis, and TGF-β1 gene expression were assessed. Results In the Conduits coated with SDF-1/bFGF group, the mean sciatic functional index value (-88.68 ± 10.64, p = .034) and the axon number (218.8 ± 111.1, p = .049) were significantly higher than the Conduit alone group, followed by the autograft group; in addition, numerous CD34-positive cells and micro vessels were observed. TGF-β1 gene expression relative values in the Conduits with SDF-1/bFGF group at 3 days (7.99 ± 5.14, p = .049) significantly increased more than the Conduits alone group. Conclusion Nerve Conduits coated with dual controlled release of SDF-1 and bFGF promoted peripheral Nerve regeneration.
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long term efficacy and safety outcomes of transplantation of induced pluripotent stem cell derived neurospheres with bioabsorbable Nerve Conduits for peripheral Nerve regeneration in mice
2015Co-Authors: Takuya Uemura, Kiyohito Takamatsu, Mikinori Ikeda, Mitsuhiro Okada, Takuya Yokoi, Hiroaki NakamuraAbstract:The induced pluripotent stem cell (iPSc) offers great potential for cell-based therapy in regenerative medicine. We previously developed tissue-engineered bioabsorbable Nerve Conduits coated with iPSc-derived neurospheres for use in peripheral Nerve repair. Here, we examine the long-term efficacy and safety of using Nerve Conduits with iPSc technology for peripheral Nerve repair in mice. The Nerve Conduit consisted of an outer layer of a poly L-lactide mesh and an inner layer of porous sponge composed of 50% L-lactide and 50% e-caprolactone. Secondary neurospheres were derived from mouse iPScs, resuspended and cultured within the Conduit for 14 days. Conduits were implanted within surgically administered 5-mm defects in the left sciatic Nerve of mice (iPSc group; n = 14). The defects in the control group (n = 13) were reconstructed using the Nerve Conduit alone. At 4, 8, 12, 24 and 48 weeks postsurgery, motor and sensory functional recovery in the iPSc group had improved significantly more than in the control group. At 24 and 48 weeks, histological analysis revealed axonal regeneration in the Nerve Conduits of both groups. However, axonal regeneration and myelination were significantly enhanced in the iPSc group. No teratomas were identified in the iPSc group at any time point. Therefore, we here demonstrate that bioabsorbable Nerve Conduits coated with iPSc-derived neurospheres promote enhanced regeneration of peripheral Nerves and functional recovery without teratoma formation in the long term. This combination of iPSc technology and bioabsorbable Nerve Conduits has the potential to be a safe future tool for the treatment of peripheral Nerve defects.
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acceleration of peripheral Nerve regeneration using Nerve Conduits in combination with induced pluripotent stem cell technology and a basic fibroblast growth factor drug delivery system
2014Co-Authors: Mikinori Ikeda, Takuya Uemura, Kiyohito Takamatsu, Mitsuhiro Okada, Kenichi Kazuki, Yoshito Ikada, Yasuhiko Tabata, Hiroaki NakamuraAbstract:Various modifications including addition of Schwann cells or incorporation of growth factors with bioabsorbable Nerve Conduits have been explored as options for peripheral Nerve repair. However, no reports of Nerve Conduits containing both supportive cells and growth factors have been published as a regenerative therapy for peripheral Nerves. In the present study, sciatic Nerve gaps in mice were reconstructed in the following groups: Nerve Conduit alone (control group), Nerve Conduit coated with induced pluripotent stem cell (iPSc)-derived neurospheres (iPSc group), Nerve Conduit coated with iPSc-derived neurospheres and basic fibroblast growth factor (bFGF)-incorporated gelatin microspheres (iPSc + bFGF group), and autograft. The fastest functional recovery and the greatest axon regeneration occurred in the autograft group, followed in order by the iPSc + bFGF group, iPSc group, and control group until 12 weeks after reconstruction. Thus, peripheral Nerve regeneration using Nerve Conduits and functional recovery in mice was accelerated by a combination of iPSc-derived neurospheres and a bFGF drug delivery system. The combination of all three fundamental methodologies, iPSc technology for supportive cells, bioabsorbable Nerve Conduits for scaffolds, and a bFGF drug delivery system for growth factors, was essential for peripheral Nerve regenerative therapy.
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a tissue engineered bioabsorbable Nerve Conduit created by three dimensional culture of induced pluripotent stem cell derived neurospheres
2011Co-Authors: Takuya Uemura, Kiyohito Takamatsu, Mikinori Ikeda, Mitsuhiro Okada, Kenichi Kazuki, Yoshito Ikada, Hiroaki NakamuraAbstract:We previously reported a bioabsorbable Nerve Conduit coated with Schwann cells for the treatment of peripheral Nerve defects. Since there have been dramatic developments in induced pluripotent stem (iPS) cells in recent years, the purpose of the present study was to create a tissue-engineered Nerve Conduit coated with iPS cell-derived neurospheres. Such a Conduit was constructed by three-dimensional (3D)-culture of these cells using a bioabsorbable polymer Conduit as a scaffold. The Nerve Conduit was composed of a mesh of poly L-lactide, and a porous sponge of 50% poly L-lactide and 50% poly e-caprolactone. The primary and secondary neurospheres (PNS and SNS, respectively) induced from iPS cells were suspended in individual Conduits. The Conduits were incubated for 7 or 14 days in vitro and then evaluated using immunohistochemistry. All of the 7- and 14-day differentiated PNS and SNS were observed to have adhered to the inner surface of the Conduits and to have migrated into the inner porous sponge. The engrafted cells were positive for anti-Tuj1, -S-100 and -GFAP antibodies, indicating that their pluripotent ability to form neural or glial cells was maintained. These findings indicate the feasibility of creating Nerve Conduits coated with a 3D-culture of iPS cell-derived neurospheres for the treatment of peripheral Nerve defects.