The Experts below are selected from a list of 21018 Experts worldwide ranked by ideXlab platform
Shugo Tohyama - One of the best experts on this subject based on the ideXlab platform.
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a massive suspension culture system with metabolic purification for human pluripotent stem cell derived cardiomyocytes
Stem Cells Translational Medicine, 2014Co-Authors: Natsuko Hemmi, Shugo Tohyama, Kazuaki Nakajima, Hideaki Kanazawa, Tomoyuki Suzuki, Fumiyuki Hattori, Tomohisa Seki, Yoshikazu Kishino, Akinori HiranoAbstract:Cardiac Regenerative Therapy with human pluripotent stem cells (hPSCs), such as human embryonic stem cells and induced pluripotent stem cells, has been hampered by the lack of efficient strategies for expanding functional cardiomyocytes (CMs) to clinically relevant numbers. The development of the massive suspension culture system (MSCS) has shed light on this critical issue, although it remains unclear how hPSCs could differentiate into functional CMs using a MSCS. The proliferative rate of differentiating hPSCs in the MSCS was equivalent to that in suspension cultures using nonadherent culture dishes, although the MSCS provided more homogeneous embryoid bodies (EBs), eventually reducing apoptosis. However, pluripotent markers such as Oct3/4 and Tra-1-60 were still expressed in EBs 2 weeks after differentiation, even in the MSCS. The remaining undifferentiated stem cells in such cultures could retain a strong potential for teratoma formation, which is the worst scenario for clinical applications of hPSC-derived CMs. The metabolic purification of CMs in glucose-depleted and lactate-enriched medium successfully eliminated the residual undifferentiated stem cells, resulting in a refined hPSC-derived CM population. In colony formation assays, no Tra-1-60-positive colonies appeared after purification. The nonpurified CMs in the MSCS produced teratomas at a rate of 60%. However, purified CMs never induced teratomas, and enriched CMs showed proper electrophysiological properties and calcium transients. Overall, the combination of a MSCS and metabolic selection is a highly effective and practical approach to purify and enrich massive numbers of functional CMs and provides an essential technique for cardiac Regenerative Therapy with hPSC-derived CMs.
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distinct metabolic flow enables large scale purification of mouse and human pluripotent stem cell derived cardiomyocytes
Cell Stem Cell, 2013Co-Authors: Shugo Tohyama, Tomoyuki Suzuki, Fumiyuki Hattori, Motoaki Sano, Takako Hishiki, Yoshiko Nagahata, Tomomi Matsuura, Hisayuki Hashimoto, Hiromi YamashitaAbstract:Heart disease remains a major cause of death despite advances in medical technology. Heart-Regenerative Therapy that uses pluripotent stem cells (PSCs) is a potentially promising strategy for patients with heart disease, but the inability to generate highly purified cardiomyocytes in sufficient quantities has been a barrier to realizing this potential. Here, we report a nongenetic method for mass-producing cardiomyocytes from mouse and human PSC derivatives that is based on the marked biochemical differences in glucose and lactate metabolism between cardiomyocytes and noncardiomyocytes, including undifferentiated cells. We cultured PSC derivatives with glucose-depleted culture medium containing abundant lactate and found that only cardiomyocytes survived. Using this approach, we obtained cardiomyocytes of up to 99% purity that did not form tumors after transplantation. We believe that our technological method broadens the range of potential applications for purified PSC-derived cardiomyocytes and could facilitate progress toward PSC-based cardiac Regenerative Therapy.
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abstract 12671 distinct metabolic flow enables large scale purification of pluripotent stem cell derived cardiomyocytes
Circulation, 2011Co-Authors: Shugo Tohyama, Fumiyuki Hattori, Motoaki Sano, Takako Hishiki, Yoshiko Nagahata, Tomofumi Tanaka, Shinsuke Yuasa, Makoto Suematsu, Keiichi FukudaAbstract:Background Mass production of highly purified cardiomyocytes is a critical bottleneck in realizing heart Regenerative Therapy. Our recently established non-genetic purification method of cardiomyoc...
Robert J Genco - One of the best experts on this subject based on the ideXlab platform.
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platelet derived growth factor modulated guided tissue Regenerative Therapy
Journal of Periodontology, 1995Co-Authors: Moonil Cho, Wenlang Lin, Robert J GencoAbstract:The goal of this study was to develop an effective Regenerative Therapy capable of achieving periodontal regeneration of Class III furcation defects. We attempted to achieve this goal by combining three therapeutic approaches. First, the lesion was protected by an expanded polytetrafluoroethylene barrier membrane that prevents migration of gingival fibroblasts as well as osteogenic cells from the mucoperiosteal flaps. Second, platelet-derived growth factor-BB (PDGF-BB), which has potent chemotactic and mitogenic effects on periodontal ligament fibroblasts (PDL), was used to promote migration of fibroblasts and their proliferation on the root surface. Third, the root surface, demineralized by citric acid conditioning, was chosen as the primary site for PDGF-BB application. The demineralized root surface appeared to have the capability of providing a sustained release of the applied growth factor. This seemed to facilitate rapid repopulation of PDL fibroblasts on the root surface and new PDL formation in th...
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periodontal regeneration in class iii furcation defects of beagle dogs using guided tissue Regenerative Therapy with platelet derived growth factor
Journal of Periodontology, 1995Co-Authors: Joonbong Park, Masahiro Matsuura, Ola M Norderyd, Robert J GencoAbstract:We developed an effective Regenerative Therapy, referred to as platelet-derived growth factor-BB (PDGF-BB)-modulated guided tissue Regenerative (GTR) Therapy (PGTR), capable of achieving periodontal regeneration of horizontal (Class III) furcation defects in the beagle dog. To determine its efficacy, repair and regeneration of horizontal furcation defects by P-GTR Therapy and GTR Therapy were compared. Chronically inflamed horizontal furcation defects were created around the second (P2) and fourth mandibular premolare (P4). After demineralization of the root surfaces with citric acid, the surfaces of left P2 and P4 were treated with PDGF-BB (P-GTR Therapy) and those of contralateral teeth were treated with vehicle only (GTR Therapy). Periodontal membranes were placed and retained 0.5 mm above the cemento-enamel junction for both groups. The mucoperiosteal flap was sutured in a coronal position and plaque control was achieved by daily irrigation with 2% chlorhexidine gluconate. At 5, 8, and 11 weeks, two a...
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periodontal regeneration in class iii furcation defects of beagle dogs using guided tissue Regenerative Therapy with platelet derived growth factor
Journal of Periodontology, 1995Co-Authors: Joonbong Park, Wenlang Lin, Robert J Genco, Masahiro Matsuura, Ola M Norderyd, Kyungyoon Han, Moonil ChoAbstract:We developed an effective Regenerative Therapy, referred to as platelet-derived growth factor-BB (PDGF-BB)-modulated guided tissue Regenerative (GTR) Therapy (P-GTR), capable of achieving periodontal regeneration of horizontal (Class III) furcation defects in the beagle dog. To determine its efficacy, repair and regeneration of horizontal furcation defects by P-GTR Therapy and GTR Therapy were compared. Chronically inflamed horizontal furcation defects were created around the second (P2) and fourth mandibular premolars (P4). After demineralization of the root surfaces with citric acid, the surfaces of left P2 and P4 were treated with PDGF-BB (P-GTR Therapy) and those of contralateral teeth were treated with vehicle only (GTR Therapy). Periodontal membranes were placed and retained 0.5 mm above the cemento-enamel junction for both groups. The mucoperiosteal flap was sutured in a coronal position and plaque control was achieved by daily irrigation with 2% chlorhexidine gluconate. At 5, 8, and 11 weeks, two animals each were sacrificed by perfusion with 2.5% glutaraldehyde through the carotid arteries, and the lesions were sliced mesio-distally, demineralized, dehydrated, and embedded. Periodontal healing and regeneration after GTR and P-GTR Therapy were compared by histomorphometric as well as morphological analysis. Morphometric analysis for each time period was performed on the pooled samples of P2 and P4. Five weeks after both therapies, the lesions were filled primarily by tissue-free area, epithelium, inflamed tissue, and a small amount of newly formed fibrous connective tissue. At 8 and 11 weeks after P-GTR Therapy, there was a statistically greater amount of bone and periodontal ligament formed in the lesions. The newly formed bone filled 80% of the lesion at 8 weeks and 87% at 11 weeks with P-GTR Therapy, compared to 14% of the lesion at 8 weeks and 60% at 11 weeks with GTR Therapy. Also, with P-GTR Therapy there was less epithelium and tissue-free area, less inflamed tissue, and less connective tissue. Morphological analysis indicated that the defects around P2 revealed faster periodontal repair and regeneration than those around P4. While the lesions around P2 were effectively regenerated by 11 weeks even after GTR Therapy, those around P4 failed to regenerate. On the other hand, P-GTR Therapy further promoted periodontal repair and regeneration so that at 8 weeks the lesions around P2 and P4 demonstrated complete and nearly complete regeneration, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
Gregg M Janowski - One of the best experts on this subject based on the ideXlab platform.
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recent advances in the development of gtr gbr membranes for periodontal regeneration a materials perspective
Dental Materials, 2012Co-Authors: Marco C Bottino, Vinoy Thomas, Gudrun Schmidt, Yogesh K Vohra, Michael J Kowolik, Gregg M JanowskiAbstract:UNLABELLED: Periodontitis is a major chronic inflammatory disorder that can lead to the destruction of the periodontal tissues and, ultimately, tooth loss. To date, flap debridement and/or flap curettage and periodontal Regenerative Therapy with membranes and bone grafting materials have been employed with distinct levels of clinical success. Current resorbable and non-resorbable membranes act as a physical barrier to avoid connective and epithelial tissue down-growth into the defect, favoring the regeneration of periodontal tissues. These conventional membranes possess many structural, mechanical, and bio-functional limitations and the "ideal" membrane for use in periodontal Regenerative Therapy has yet to be developed. Based on a graded-biomaterials approach, we have hypothesized that the next-generation of guided tissue and guided bone regeneration (GTR/GBR) membranes for periodontal tissue engineering will be a biologically active, spatially designed and functionally graded nanofibrous biomaterial that closely mimics the native extra-cellular matrix (ECM). OBJECTIVE: This review is presented in three major parts, including (1) a brief overview of the periodontium and its pathological conditions, (2) currently employed therapeutics used to regenerate the distinct periodontal tissues, and (3) a review of commercially available GTR/GBR membranes as well as the recent advances on the processing and characterization of GTR/GBR membranes from a materials perspective. SIGNIFICANCE: Studies of spatially designed and functionally graded membranes (FGM) and in vitro antibacterial/cell-related research are addressed. Finally, as a future outlook, the use of hydrogels in combination with scaffold materials is highlighted as a promising approach for periodontal tissue engineering.
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recent advances in the development of gtr gbr membranes for periodontal regeneration a materials perspective
Dental Materials, 2012Co-Authors: Marco C Bottino, Vinoy Thomas, Gudrun Schmidt, Yogesh K Vohra, Michael J Kowolik, Tienmin G Chu, Gregg M JanowskiAbstract:Abstract Periodontitis is a major chronic inflammatory disorder that can lead to the destruction of the periodontal tissues and, ultimately, tooth loss. To date, flap debridement and/or flap curettage and periodontal Regenerative Therapy with membranes and bone grafting materials have been employed with distinct levels of clinical success. Current resorbable and non-resorbable membranes act as a physical barrier to avoid connective and epithelial tissue down-growth into the defect, favoring the regeneration of periodontal tissues. These conventional membranes possess many structural, mechanical, and bio-functional limitations and the “ideal” membrane for use in periodontal Regenerative Therapy has yet to be developed. Based on a graded-biomaterials approach, we have hypothesized that the next-generation of guided tissue and guided bone regeneration (GTR/GBR) membranes for periodontal tissue engineering will be a biologically active, spatially designed and functionally graded nanofibrous biomaterial that closely mimics the native extra-cellular matrix (ECM). Objective This review is presented in three major parts, including (1) a brief overview of the periodontium and its pathological conditions, (2) currently employed therapeutics used to regenerate the distinct periodontal tissues, and (3) a review of commercially available GTR/GBR membranes as well as the recent advances on the processing and characterization of GTR/GBR membranes from a materials perspective. Significance Studies of spatially designed and functionally graded membranes (FGM) and in vitro antibacterial/cell-related research are addressed. Finally, as a future outlook, the use of hydrogels in combination with scaffold materials is highlighted as a promising approach for periodontal tissue engineering.
Fumiyuki Hattori - One of the best experts on this subject based on the ideXlab platform.
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a massive suspension culture system with metabolic purification for human pluripotent stem cell derived cardiomyocytes
Stem Cells Translational Medicine, 2014Co-Authors: Natsuko Hemmi, Shugo Tohyama, Kazuaki Nakajima, Hideaki Kanazawa, Tomoyuki Suzuki, Fumiyuki Hattori, Tomohisa Seki, Yoshikazu Kishino, Akinori HiranoAbstract:Cardiac Regenerative Therapy with human pluripotent stem cells (hPSCs), such as human embryonic stem cells and induced pluripotent stem cells, has been hampered by the lack of efficient strategies for expanding functional cardiomyocytes (CMs) to clinically relevant numbers. The development of the massive suspension culture system (MSCS) has shed light on this critical issue, although it remains unclear how hPSCs could differentiate into functional CMs using a MSCS. The proliferative rate of differentiating hPSCs in the MSCS was equivalent to that in suspension cultures using nonadherent culture dishes, although the MSCS provided more homogeneous embryoid bodies (EBs), eventually reducing apoptosis. However, pluripotent markers such as Oct3/4 and Tra-1-60 were still expressed in EBs 2 weeks after differentiation, even in the MSCS. The remaining undifferentiated stem cells in such cultures could retain a strong potential for teratoma formation, which is the worst scenario for clinical applications of hPSC-derived CMs. The metabolic purification of CMs in glucose-depleted and lactate-enriched medium successfully eliminated the residual undifferentiated stem cells, resulting in a refined hPSC-derived CM population. In colony formation assays, no Tra-1-60-positive colonies appeared after purification. The nonpurified CMs in the MSCS produced teratomas at a rate of 60%. However, purified CMs never induced teratomas, and enriched CMs showed proper electrophysiological properties and calcium transients. Overall, the combination of a MSCS and metabolic selection is a highly effective and practical approach to purify and enrich massive numbers of functional CMs and provides an essential technique for cardiac Regenerative Therapy with hPSC-derived CMs.
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distinct metabolic flow enables large scale purification of mouse and human pluripotent stem cell derived cardiomyocytes
Cell Stem Cell, 2013Co-Authors: Shugo Tohyama, Tomoyuki Suzuki, Fumiyuki Hattori, Motoaki Sano, Takako Hishiki, Yoshiko Nagahata, Tomomi Matsuura, Hisayuki Hashimoto, Hiromi YamashitaAbstract:Heart disease remains a major cause of death despite advances in medical technology. Heart-Regenerative Therapy that uses pluripotent stem cells (PSCs) is a potentially promising strategy for patients with heart disease, but the inability to generate highly purified cardiomyocytes in sufficient quantities has been a barrier to realizing this potential. Here, we report a nongenetic method for mass-producing cardiomyocytes from mouse and human PSC derivatives that is based on the marked biochemical differences in glucose and lactate metabolism between cardiomyocytes and noncardiomyocytes, including undifferentiated cells. We cultured PSC derivatives with glucose-depleted culture medium containing abundant lactate and found that only cardiomyocytes survived. Using this approach, we obtained cardiomyocytes of up to 99% purity that did not form tumors after transplantation. We believe that our technological method broadens the range of potential applications for purified PSC-derived cardiomyocytes and could facilitate progress toward PSC-based cardiac Regenerative Therapy.
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abstract 12671 distinct metabolic flow enables large scale purification of pluripotent stem cell derived cardiomyocytes
Circulation, 2011Co-Authors: Shugo Tohyama, Fumiyuki Hattori, Motoaki Sano, Takako Hishiki, Yoshiko Nagahata, Tomofumi Tanaka, Shinsuke Yuasa, Makoto Suematsu, Keiichi FukudaAbstract:Background Mass production of highly purified cardiomyocytes is a critical bottleneck in realizing heart Regenerative Therapy. Our recently established non-genetic purification method of cardiomyoc...
Keiichi Fukuda - One of the best experts on this subject based on the ideXlab platform.
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abstract 12671 distinct metabolic flow enables large scale purification of pluripotent stem cell derived cardiomyocytes
Circulation, 2011Co-Authors: Shugo Tohyama, Fumiyuki Hattori, Motoaki Sano, Takako Hishiki, Yoshiko Nagahata, Tomofumi Tanaka, Shinsuke Yuasa, Makoto Suematsu, Keiichi FukudaAbstract:Background Mass production of highly purified cardiomyocytes is a critical bottleneck in realizing heart Regenerative Therapy. Our recently established non-genetic purification method of cardiomyoc...
