The Experts below are selected from a list of 6858 Experts worldwide ranked by ideXlab platform
Yoshiki Sawa - One of the best experts on this subject based on the ideXlab platform.
-
Autologous Skeletal Myoblast sheet implantation for pediatric dilated cardiomyopathy: A case report
General Thoracic and Cardiovascular Surgery, 2020Co-Authors: Kanta Araki, Masaki Taira, Shigeru Miyagawa, Tomomitsu Kanaya, Naoki Okuda, Koichi Toda, Toru Kuratani, Takayoshi Ueno, Yoshiki SawaAbstract:Background In children with dilated cardiomyopathy, heart transplantation is the last treatment option. However, new regenerative treatments, such as cell therapy, have attracted scientific attention. We have previously demonstrated the efficacy of autologous Skeletal Myoblast sheet implantation for treatment of ischemic and dilated cardiomyopathy in adults. Because of the mechanism underlying this cell therapy, a similar effectiveness is expected for patients with pediatric dilated cardiomyopathy. Case Herein, we describe the case of a child with dilated cardiomyopathy who underwent an autologous Skeletal Myoblast sheet implantation, which proved to be safe, and led to sustained maintenance and improvements in cardiac function and clinical status.
-
Abstract 16376: Long-Term Results of Autologous Skeletal Myoblast Cell-Sheet Transplantation for End-Stage Ischemic Cardiomyopathy
Circulation, 2019Co-Authors: Satoshi Kainuma, Shigeru Miyagawa, Koichi Toda, Takuji Kawamura, Yasushi Yoshikawa, Hiroki Hata, Daisuke Yoshioka, Ai Kawamura, Yoshiki SawaAbstract:Introduction: The recent Phase I clinical trial demonstrated that the Skeletal Myoblast cell-sheet transplantation was feasible and safe in cardiomyopathy patients, however its long-term therapeuti...
-
abstract 14672 a pivotal role of synthetic smooth muscle cells activated by hepatocyte growth factor in extracellular matrix modulation related functional recovery post cell sheet transplantation in a rat chronic myocardial infarction model
Circulation, 2016Co-Authors: Motoko Shiozaki, Shigeru Miyagawa, Daisuke Yoshioka, Atsuhiro Saito, Satsuki Fukushima, Yoshiki Sakai, Kunio Matsumoto, Yoshiki SawaAbstract:Background: Transplantation of autologous Skeletal Myoblast cell (SMB)-sheet has been shown to upregulate intramyocardial expression of various factors including hepatocyte growth factor (HGF) and ...
-
abstract 20417 muscle derived new cell population has therapeutic potentials through paracrine effects in cell sheet transplantation in a rat ischemic cardiomyopathy model
Circulation, 2016Co-Authors: Hiroko Iseoka, Shigeru Miyagawa, Atsuhiro Saito, Satsuki Fukushima, Shigeo Masuda, Yoshiki SawaAbstract:Background: Transplantation of autologous Skeletal Myoblast (SMB) cell-sheets has been shown to produce therapeutic effects via paracrine effects in ischemic cardiomyopathy (ICM). Although purity o...
-
improved clinical course of autologous Skeletal Myoblast sheet tcd 51073 transplantation when compared to a propensity score matched cardiac resynchronization therapy population
Journal of Artificial Organs, 2016Co-Authors: Teruhiko Imamura, Shigeru Miyagawa, Yoshiki Sawa, Koichiro Kinugawa, Yasushi Sakata, Kenji Yamazaki, Minoru OnoAbstract:We recently reported a multi-center, single-arm, phase II study that evaluated the efficacy and safety of autologous Skeletal Myoblast sheet (TCD-51073) transplantation. The advantage of this procedure over a control group has not yet been analyzed. Seven patients with advanced heart failure due to ischemic etiology (TCD-51073 group, New York Heart Association (NYHA) class III; left ventricular ejection fraction (LVEF) <35 %) refractory to optimal medical and coronary revascularization therapy, received TCD-51073 at 3 study centers between 2012 and 2013 with a 2-year follow-up period. As previously reported, 112 patients received cardiac resynchronization therapy (CRT) with follow-up at the University of Tokyo Hospital between 2007 and 2014. Of them, 21 patients were selected for the control group by propensity score matching. No significant difference in baseline variables between the groups was observed. LVEF and NYHA class improved significantly in the TCD-51073 group during the 6-month study period (p < 0.05). During the 2-year follow-up, 7 patients (33 %) in the CRT group and no patient in the TCD-51073 group died due to cardiac disease or received VAD implantation (p = 0.128 by the log-rank test). In conclusion, transplantation of TCD-51073 is clinically advantageous in facilitating LV reverse remodeling, improving HF symptoms, and preventing cardiac death in patients with ischemic etiology when compared to background-matched patients receiving CRT.
Shigeru Miyagawa - One of the best experts on this subject based on the ideXlab platform.
-
Autologous Skeletal Myoblast patch implantation prevents the deterioration of myocardial ischemia and right heart dysfunction in a pressure-overloaded right heart porcine model
PloS one, 2021Co-Authors: Kanta Araki, Masaki Taira, Shigeru Miyagawa, Koichi Toda, Toru Kuratani, Takuji Kawamura, Ryo Ishii, Tadashi Watabe, Akima Harada, Takayoshi UenoAbstract:Right ventricular dysfunction is a predictor for worse outcomes in patients with congenital heart disease. Myocardial ischemia is primarily associated with right ventricular dysfunction in patients with congenital heart disease and may be a therapeutic target for right ventricular dysfunction. Previously, autologous Skeletal Myoblast patch therapy showed an angiogenic effect for left ventricular dysfunction through cytokine paracrine effects; however, its efficacy in right ventricular dysfunction has not been evaluated. Thus, this study aimed to evaluate the angiogenic effect of autologous Skeletal Myoblast patch therapy and amelioration of metabolic and functional dysfunction, in a pressure-overloaded right heart porcine model. Pulmonary artery stenosis was induced by a vascular occluder in minipigs; after two months, autologous Skeletal Myoblast patch implantation on the right ventricular free wall was performed (n = 6). The control minipigs underwent a sham operation (n = 6). The autologous Skeletal Myoblast patch therapy alleviated right ventricular dilatation and ameliorated right ventricular systolic and diastolic dysfunction. 11C-acetate kinetic analysis using positron emission tomography showed improvement in myocardial oxidative metabolism and myocardial flow reserve after cell patch implantation. On histopathology, a higher capillary density and vascular maturity with reduction of myocardial ischemia were observed after patch implantation. Furthermore, analysis of mRNA expression revealed that the angiogenic markers were upregulated, and ischemic markers were downregulated after patch implantation. Thus, autologous Skeletal Myoblast patch therapy ameliorated metabolic and functional dysfunction in a pressure-overloaded right heart porcine model, by alleviating myocardial ischemia through angiogenesis.
-
long term outcomes of autologous Skeletal Myoblast cell sheet transplantation for end stage ischemic cardiomyopathy
Molecular Therapy, 2021Co-Authors: Satoshi Kainuma, Shigeru Miyagawa, Koichi Toda, Takuji Kawamura, Yasushi Yoshikawa, Hiroki Hata, Daisuke Yoshioka, Ai Kawamura, Noriyuki Kashiyama, Yoshito ItoAbstract:We evaluated the cardiac function recovery following Skeletal Myoblast cell-sheet transplantation and the long-term outcomes after applying this treatment in 23 patients with ischemic cardiomyopathy. We defined patients as "responders" when their left ventricular ejection fraction remained unchanged or improved at 6 months after treatment. At 6 months, 16 (69.6%) patients were defined as responders, and the average increase in left ventricular ejection fraction was 4.9%. The responders achieved greater improvement degrees in left ventricular and hemodynamic function parameters, and they presented improved exercise capacity. During the follow-up period (56 ± 28 months), there were four deaths and the overall 5-year survival rate was 95%. Although the responders showed higher freedom from mortality and/or heart failure admission (5-year, 81% versus 0%; p = 0.0002), both groups presented an excellent 5-year survival rate (5-year, 93% versus 100%; p = 0.297) that was higher than that predicted using the Seattle Heart Failure Model. The stepwise logistic regression analysis showed that the preoperative estimated glomerular filtration rate and the left ventricular end-systolic volume index were independently associated with the recovery progress. Approximately 70% of patients with "no-option" ischemic cardiomyopathy responded well to the cell-sheet transplantation. Preoperative renal and left ventricular function might predict the patients' response to this treatment.
-
Autologous Skeletal Myoblast sheet implantation for pediatric dilated cardiomyopathy: A case report
General Thoracic and Cardiovascular Surgery, 2020Co-Authors: Kanta Araki, Masaki Taira, Shigeru Miyagawa, Tomomitsu Kanaya, Naoki Okuda, Koichi Toda, Toru Kuratani, Takayoshi Ueno, Yoshiki SawaAbstract:Background In children with dilated cardiomyopathy, heart transplantation is the last treatment option. However, new regenerative treatments, such as cell therapy, have attracted scientific attention. We have previously demonstrated the efficacy of autologous Skeletal Myoblast sheet implantation for treatment of ischemic and dilated cardiomyopathy in adults. Because of the mechanism underlying this cell therapy, a similar effectiveness is expected for patients with pediatric dilated cardiomyopathy. Case Herein, we describe the case of a child with dilated cardiomyopathy who underwent an autologous Skeletal Myoblast sheet implantation, which proved to be safe, and led to sustained maintenance and improvements in cardiac function and clinical status.
-
Abstract 16376: Long-Term Results of Autologous Skeletal Myoblast Cell-Sheet Transplantation for End-Stage Ischemic Cardiomyopathy
Circulation, 2019Co-Authors: Satoshi Kainuma, Shigeru Miyagawa, Koichi Toda, Takuji Kawamura, Yasushi Yoshikawa, Hiroki Hata, Daisuke Yoshioka, Ai Kawamura, Yoshiki SawaAbstract:Introduction: The recent Phase I clinical trial demonstrated that the Skeletal Myoblast cell-sheet transplantation was feasible and safe in cardiomyopathy patients, however its long-term therapeuti...
-
abstract 14672 a pivotal role of synthetic smooth muscle cells activated by hepatocyte growth factor in extracellular matrix modulation related functional recovery post cell sheet transplantation in a rat chronic myocardial infarction model
Circulation, 2016Co-Authors: Motoko Shiozaki, Shigeru Miyagawa, Daisuke Yoshioka, Atsuhiro Saito, Satsuki Fukushima, Yoshiki Sakai, Kunio Matsumoto, Yoshiki SawaAbstract:Background: Transplantation of autologous Skeletal Myoblast cell (SMB)-sheet has been shown to upregulate intramyocardial expression of various factors including hepatocyte growth factor (HGF) and ...
Magdi H Yacoub - One of the best experts on this subject based on the ideXlab platform.
-
a factor underlying late phase arrhythmogenicity after cell therapy to the heart global downregulation of connexin43 in the host myocardium after Skeletal Myoblast transplantation
Circulation, 2008Co-Authors: Steven R Coppen, Magdi H Yacoub, Satsuki Fukushima, Yasunori Shintani, Kunihiko Takahashi, Anabel Varelacarver, Husein Salem, Kenta Yashiro, Ken SuzukiAbstract:Background— Arrhythmia occurrence is a variable but serious concern of cell therapy for treating heart failure. Using a rat postinfarction chronic heart failure model, we compared Skeletal Myoblast (SMB) with bone marrow cell (BMC) injection to highlight donor cell-specific, late-phase arrhythmogenesis and the underlying factors. Methods and Results— SMBs or BMCs derived from male GFP-transgenic rats, or PBS were injected intramyocardially into female rat hearts 3 weeks after coronary artery occlusion. At 28 days after injection, echocardiography showed that the left ventricular ejection fraction was significantly improved in both the SMB and BMC groups, compared to PBS control despite poor graft survival as assessed by PCR for the male-specific gene. Radio-telemetry analysis revealed that the SMB group displayed a higher occurrence of ventricular premature contractions with an elongation of the QRS complex and the hearts were more susceptible to isopreterenol-induced ventricular tachycardia compared to t...
-
evaluation of frequency type and function of gap junctions between Skeletal Myoblasts overexpressing connexin43 and cardiomyocytes relevance to cell transplantation
The FASEB Journal, 2006Co-Authors: Mark A Stagg, Ken Suzuki, Nigel J Brand, Magdi H Yacoub, Satsuki Fukushima, Steven R Coppen, Anabel Varelacarver, Joon Lee, Cesare M TerraccianoAbstract:SPECIFIC AIMSArrhythmias after Skeletal Myoblast (SM) transplantation are likely to be the consequence of the absence of or inappropriate intercellular communication between the host cardiomyocytes...
-
Cell transplantation for the treatment of acute myocardial infarction using vascular endothelial growth factor-expressing Skeletal Myoblasts.
Circulation, 2001Co-Authors: Ken Suzuki, Ryszard T Smolenski, Bari Murtuza, Ivan A. Sammut, Noriko Suzuki, Yasufumi Kaneda, Magdi H YacoubAbstract:Background Vascular endothelial growth factor (VEGF) is a promising reagent for inducing myocardial angiogenesis. Skeletal Myoblast transplantation has been shown to improve cardiac function in chronic heart failure models by regenerating muscle. We hypothesized that transplantation of VEGF-expressing Myoblasts could effectively treat acute myocardial infarction by providing VEGF-induced cardioprotection through vasodilatation in the early phase, followed by angiogenesis effects in salvaging ischemic host myocardium combined with the functional benefits of newly formed, Skeletal Myoblast-derived muscle in the later phase. Methods and Results Primary rat Skeletal Myoblasts were transfected with the human VEGF165 gene using hemagglutinating virus of Japan-liposome with >95% transfection efficiency. Four million of these Myoblasts (VEGF group), control-transfected Myoblasts (control group), or medium only (medium group) was injected into syngeneic rat hearts 1 hour after left coronary artery occlusion. Myoca...
-
Intracoronary Infusion of Skeletal Myoblasts Improves Cardiac Function in Doxorubicin-Induced Heart Failure
Circulation, 2001Co-Authors: Ken Suzuki, Ryszard T Smolenski, Bari Murtuza, Noriko Suzuki, Magdi H YacoubAbstract:Background Skeletal Myoblast transplantation is promising for the treatment of end-stage heart failure. Direct intramyocardial injection is useful for local cell delivery but may not be effective in global dissemination of cells into the heart, which would be advantageous in treating generalized cardiac dysfunction as in dilated cardiomyopathy. We hypothesized that intracoronary infusion of Myoblasts would disseminate cells more effectively, leading to functional improvement in global heart failure. Methods and Results Heart failure was induced by the intraperitoneal administration of doxorubicin (total dose 15 mg/kg) in rat. One million primary Skeletal Myoblasts were then infused via the coronary arteries of an excised, failing doxorubicin-treated heart. After incubation under increased intracoronary pressure, the hearts were subsequently transplanted into syngeneic recipients. For the control group, doxorubicin-treated hearts were infused with medium only and transplanted. Four weeks after transplantation, Langendorff perfusion demonstrated that both maximum dP/dt (2797.6±103.3 versus 2326.9±133.1 mm Hg/s, P =0.01) and minimum dP/dt (−2067.4±88.1 versus −1718.8±91.3 mm Hg/s, P =0.02) were improved in Myoblast-transplanted hearts compared with medium-infused hearts. This was associated with a sharper slope of the left ventricular developed pressure-volume curve and a reduced slope of the end-diastolic pressure-volume relation in the Myoblast-transplanted hearts. Immunohistochemistry for Skeletal myosin heavy chain showed that globally disseminated Myoblasts had survived and differentiated into multinucleated myotubes that had aligned with the cardiac fiber axis within host myocardium. No significant myocardial infarction was observed. Conclusions We demonstrated the feasibility and efficiency of Skeletal Myoblast transplantation via the intracoronary route as a promising strategy for improving cardiac function in global heart failure.
-
Overexpression of connexin 43 in Skeletal Myoblasts: Relevance to cell transplantation to the heart.
The Journal of thoracic and cardiovascular surgery, 2001Co-Authors: Ken Suzuki, Bari Murtuza, Nigel J Brand, Sean P. Allen, Mahboob A. Khan, Aldo O. Farrell, Reida El Oakley, Magdi H YacoubAbstract:Abstract Objective: Skeletal Myoblast transplantation is a promising strategy for treating end-stage heart failure. One potential problem in the development of functional, synchronously contracting grafts is the degree of intercellular communication between grafted Myoblasts and host cardiomyocytes. Thus it is expected that enhancement of intercellular gap junction formation would result in improved efficiency of Skeletal Myoblast transplantation. In this study we investigated whether Myoblasts overexpressing connexin 43, a major cardiac gap junction protein, would enhance this intercellular communication. Methods and Results: L6 rat Skeletal Myoblast cell lines overexpressing connexin 43 were generated by means of gene transfection and clonal selection. Connexin 43 overexpression of these Myoblasts, which continued both in undifferentiated and differentiated states (up to 17-fold greater protein level in comparison with control-transfected Myoblasts, as measured with Western blotting), was observed on cell surfaces where gap junctions should exist. Both dye microinjection and scrape loading with fluorescent dyes showed enhancement in intercellular dye transfer between connexin 43–transfected Myoblasts compared with that found in control-transfected cells. Morphologically, these Myoblasts fused and differentiated into multinucleated myotubes more rapidly, demonstrating a higher level of cellular creatine kinase activity as a marker of myogenic differentiation throughout the culture period compared with that of control-transfected Myoblasts. Conclusions: We have generated connexin 43–overexpressing Skeletal Myoblast cell lines that resulted in improved formation of functional intercellular gap junctions, which could be relevant to synchronous contraction of grafted Myoblasts in the heart. In addition, these cells demonstrated more rapid differentiation, which would also be advantageous in a graft for transplantation to the heart.
Philippe Menasche - One of the best experts on this subject based on the ideXlab platform.
-
Self-assembling peptide nanofibers and Skeletal Myoblast transplantation in infarcted myocardium.
Journal of biomedical materials research. Part B Applied biomaterials, 2008Co-Authors: Gilbert Dubois, Albert Hagège, Patrick Bruneval, Valérie Bellamy, Séverine Peyrard, Laurent Sabbah, Vincent F. M. Segers, Richard T. Lee, Philippe MenascheAbstract:Cell transplantation is currently limited by poor graft retention and survival in the postinfarction scar. Because this issue could potentially be addressed by embedding cells in bioinjectable scaffolds and boosting cell survival pathways, we induced a myocardial infarction in 72 rats to assess the effects of different self-assembling peptides with or without platelet-derived growth factor (PDGF-BB) on survival of transplanted Skeletal Myoblasts. Two weeks after coronary artery ligation, rats were randomized to receive in-scar injections of culture medium (controls, n = 11), self-assembling peptide (RAD16-I) nanofibers (NF, n = 9), Skeletal Myoblasts (n = 12), or Skeletal Myoblasts in combination with NF (n = 8). In separate experiments with different self-assembling peptides (RAD16-II), rats received in-scar injections of culture medium (controls, n = 6), Skeletal Myoblasts (n = 10), PDGF-loaded peptides (n = 7), or Skeletal Myoblasts (5 x 10(6)) in combination with PDGF-loaded peptides (n = 9). After 1 month, left ventricular function, as assessed by echocardiography, was not improved in either of the experimental groups compared with controls. This correlated with the failure of RAD16-I peptides or PDGF-loaded RAD16-II peptides to improve Myoblast survival despite a greater angiogenesis. In vitro experiments confirmed that the number of Myoblasts decreased over time when seeded on nanofiber gels. These data suggest that the optimal use of biomaterial scaffolds for survival of transplanted cells will require specific tailoring of the biomaterial to the cell type.
-
Can erythropoietin improve Skeletal Myoblast engraftment in infarcted myocardium
Interactive cardiovascular and thoracic surgery, 2007Co-Authors: Sylvain Chanséaume, Albert Hagège, Patrick Bruneval, Kasra Azarnoush, Agnès Maurel, Valérie Bellamy, Séverine Peyrard, Philippe MenascheAbstract:The benefits of Skeletal Myoblast transplantation are limited by the high rate of early cell death which is partly of ischemic origin. We, therefore, assessed whether graft survival could be improved by the additional use of the angiogenic cytokine erythropoietin (EPO). Thirty-five Lewis rats underwent coronary artery ligation and, two weeks later, were randomized to receive in-scar injections of control medium, Skeletal Myoblasts (5x10(6)) or Skeletal Myoblasts with EPO started the day before transplantation and continued for two weeks (500 U/kg three times a week). A fourth group was treated by EPO alone without injections. Function was assessed by 2D echocardiography before transplantation and one month thereafter. Compared with controls and hearts treated by EPO-alone, those transplanted with Myoblasts yielded a significantly better recovery of LV ejection fraction, irrespective of whether they had received EPO or not. Neither the area of Myoblast engraftment, nor angiogenesis differed between the Myoblast-alone and the Myoblast+EPO groups. Apoptosis was hardly detectable and, therefore, unaffected by EPO therapy. In this model, EPO failed to improve Myoblast engraftment and postinfarction LV function. These negative findings justify to pursue the search for alternate cell survival-enhancing strategies.
-
Institutional report - Experimental Can erythropoietin improve Skeletal Myoblast engraftment in infarcted myocardium?
2007Co-Authors: Kasra Azarnoush, Patrick Bruneval, Philippe MenascheAbstract:The benefits of Skeletal Myoblast transplantation are limited by the high rate of early cell death which is partly of ischemic origin. We, therefore, assessed whether graft survival could be improved by the additional use of the angiogenic cytokine erythropoietin (EPO). Thirtyfive Lewis rats underwent coronary artery ligation and, two weeks later, were randomized to receive in-scar injections of control medium, Skeletal Myoblasts (5=10 ) or Skeletal Myoblasts with EPO started the day before transplantation and continued for two weeks (500 Uykg 6
-
Construction of Skeletal Myoblast-Based Polyurethane Scaffolds for Myocardial Repair
Artificial organs, 2007Co-Authors: Matthias Siepe, Philippe Menasche, Marie-noëlle Giraud, Elisabeth Liljensten, Urs E. Nydegger, Thierry Carrel, Hendrik T. TevaearaiAbstract:Intramyocardial transplantation of Skeletal Myoblasts augments postinfarction cardiac function. However, poor survival of injected cells limits this therapy. It is hypothesized that implantation of Myoblast-based scaffolds would result in greater cell survival. Rat Skeletal Myoblasts were seeded on highly porous polyurethane (PU) scaffolds (7.5 x 7.5 x 2.0 mm). The effect of several scaffold pretreatments, initial cell densities, and culture periods was tested by DNA-based cell count and viability assessment. Seeded PU scaffolds were implanted on infarcted hearts and immunohistology was performed 4 weeks later. Precoating with laminin allowed the most favorable cell attachment. An initial inoculation with 5 x 10(6) cells followed by a 15-day culture period resulted in optimal Myoblast proliferation. Four weeks after their implantation in rats, numerous Myoblasts were found throughout the seeded patches although no sign of differentiation could be observed. This Myoblast seeding technique on PU allows transfer of a large number of living Myoblasts to a damaged myocardium.
-
Skeletal Myoblast transplantation through a catheter based coronary sinus approach an effective means of improving function of infarcted myocardium
European Heart Journal, 2005Co-Authors: Camille Brasselet, Albert Hagège, Jean-thomas Vilquin, Patrick Bruneval, Claire Carrion, Alvine Bissery, Emmanuel Messas, Miguel Cortes Morichetti, Antoine Lafont, Philippe MenascheAbstract:Aims This study was designed to assess the functional effects of a transvenous coronary sinus technique of Skeletal Myoblast delivery in infarcted myocardium. Methods and results An anterior myocardial infarction was created percutaneously in 14 sheep. Simultaneously, a muscle biopsy was harvested and expanded. Two weeks later, sheep were instrumented percutaneously with a dedicated catheter incorporating an extendable needle for puncture of the venous wall and, under endovascular ultrasound guidance, a microcatheter was advanced through the needle into the target scar for cell delivery. Following the baseline echocardiographic assessment of left ventricular (LV) function, sheep were randomly allocated to receive four-staged in-scar injections of either autologous cells (n ¼ 7) or culture medium (n ¼ 7). Two months later, LV function was reassessed blindly and hearts were explanted for subsequent histological and immunohistochemical analysis. There were no acute procedural complications. Baseline LV ejection fraction (EF) was significantly lower in transplanted sheep than in controls [38% (35‐48) vs. 51% (38‐55), respectively, P ¼ 0.03; median (range)]. Two months later, LVEF was significantly higher in the transplanted group than in controls [50% (47‐56) vs. 39% (36‐47), respectively, P ¼ 0.002]. Clusters of Myoblasts were identified by histology and immunohistochemistry in three of the seven transplanted sheep. Conclusion These data suggest the functional efficacy of the transvenous coronary sinus technique as a less invasive means of cell delivery to infarcted myocardium.
Koichi Toda - One of the best experts on this subject based on the ideXlab platform.
-
Autologous Skeletal Myoblast patch implantation prevents the deterioration of myocardial ischemia and right heart dysfunction in a pressure-overloaded right heart porcine model
PloS one, 2021Co-Authors: Kanta Araki, Masaki Taira, Shigeru Miyagawa, Koichi Toda, Toru Kuratani, Takuji Kawamura, Ryo Ishii, Tadashi Watabe, Akima Harada, Takayoshi UenoAbstract:Right ventricular dysfunction is a predictor for worse outcomes in patients with congenital heart disease. Myocardial ischemia is primarily associated with right ventricular dysfunction in patients with congenital heart disease and may be a therapeutic target for right ventricular dysfunction. Previously, autologous Skeletal Myoblast patch therapy showed an angiogenic effect for left ventricular dysfunction through cytokine paracrine effects; however, its efficacy in right ventricular dysfunction has not been evaluated. Thus, this study aimed to evaluate the angiogenic effect of autologous Skeletal Myoblast patch therapy and amelioration of metabolic and functional dysfunction, in a pressure-overloaded right heart porcine model. Pulmonary artery stenosis was induced by a vascular occluder in minipigs; after two months, autologous Skeletal Myoblast patch implantation on the right ventricular free wall was performed (n = 6). The control minipigs underwent a sham operation (n = 6). The autologous Skeletal Myoblast patch therapy alleviated right ventricular dilatation and ameliorated right ventricular systolic and diastolic dysfunction. 11C-acetate kinetic analysis using positron emission tomography showed improvement in myocardial oxidative metabolism and myocardial flow reserve after cell patch implantation. On histopathology, a higher capillary density and vascular maturity with reduction of myocardial ischemia were observed after patch implantation. Furthermore, analysis of mRNA expression revealed that the angiogenic markers were upregulated, and ischemic markers were downregulated after patch implantation. Thus, autologous Skeletal Myoblast patch therapy ameliorated metabolic and functional dysfunction in a pressure-overloaded right heart porcine model, by alleviating myocardial ischemia through angiogenesis.
-
long term outcomes of autologous Skeletal Myoblast cell sheet transplantation for end stage ischemic cardiomyopathy
Molecular Therapy, 2021Co-Authors: Satoshi Kainuma, Shigeru Miyagawa, Koichi Toda, Takuji Kawamura, Yasushi Yoshikawa, Hiroki Hata, Daisuke Yoshioka, Ai Kawamura, Noriyuki Kashiyama, Yoshito ItoAbstract:We evaluated the cardiac function recovery following Skeletal Myoblast cell-sheet transplantation and the long-term outcomes after applying this treatment in 23 patients with ischemic cardiomyopathy. We defined patients as "responders" when their left ventricular ejection fraction remained unchanged or improved at 6 months after treatment. At 6 months, 16 (69.6%) patients were defined as responders, and the average increase in left ventricular ejection fraction was 4.9%. The responders achieved greater improvement degrees in left ventricular and hemodynamic function parameters, and they presented improved exercise capacity. During the follow-up period (56 ± 28 months), there were four deaths and the overall 5-year survival rate was 95%. Although the responders showed higher freedom from mortality and/or heart failure admission (5-year, 81% versus 0%; p = 0.0002), both groups presented an excellent 5-year survival rate (5-year, 93% versus 100%; p = 0.297) that was higher than that predicted using the Seattle Heart Failure Model. The stepwise logistic regression analysis showed that the preoperative estimated glomerular filtration rate and the left ventricular end-systolic volume index were independently associated with the recovery progress. Approximately 70% of patients with "no-option" ischemic cardiomyopathy responded well to the cell-sheet transplantation. Preoperative renal and left ventricular function might predict the patients' response to this treatment.
-
Autologous Skeletal Myoblast sheet implantation for pediatric dilated cardiomyopathy: A case report
General Thoracic and Cardiovascular Surgery, 2020Co-Authors: Kanta Araki, Masaki Taira, Shigeru Miyagawa, Tomomitsu Kanaya, Naoki Okuda, Koichi Toda, Toru Kuratani, Takayoshi Ueno, Yoshiki SawaAbstract:Background In children with dilated cardiomyopathy, heart transplantation is the last treatment option. However, new regenerative treatments, such as cell therapy, have attracted scientific attention. We have previously demonstrated the efficacy of autologous Skeletal Myoblast sheet implantation for treatment of ischemic and dilated cardiomyopathy in adults. Because of the mechanism underlying this cell therapy, a similar effectiveness is expected for patients with pediatric dilated cardiomyopathy. Case Herein, we describe the case of a child with dilated cardiomyopathy who underwent an autologous Skeletal Myoblast sheet implantation, which proved to be safe, and led to sustained maintenance and improvements in cardiac function and clinical status.
-
Abstract 16376: Long-Term Results of Autologous Skeletal Myoblast Cell-Sheet Transplantation for End-Stage Ischemic Cardiomyopathy
Circulation, 2019Co-Authors: Satoshi Kainuma, Shigeru Miyagawa, Koichi Toda, Takuji Kawamura, Yasushi Yoshikawa, Hiroki Hata, Daisuke Yoshioka, Ai Kawamura, Yoshiki SawaAbstract:Introduction: The recent Phase I clinical trial demonstrated that the Skeletal Myoblast cell-sheet transplantation was feasible and safe in cardiomyopathy patients, however its long-term therapeuti...
-
safety and efficacy of autologous Skeletal Myoblast sheets tcd 51073 for the treatment of severe chronic heart failure due to ischemic heart disease
Circulation, 2015Co-Authors: Yoshiki Sawa, Koichi Toda, Nobuhisa Hagiwara, Yasushi Yoshikawa, Satsuki Fukushima, Koichiro Kinugawa, Yasushi Sakata, Kenji Yamazaki, Shigeru MiyagawaAbstract:BACKGROUND: Poor survival outcomes for patients with severe heart failure (HF) and the donor shortage for heart transplantation warrant the development of myocardial regenerative therapy. We performed a multicenter, phase II study to evaluate the safety and efficacy of autologous Skeletal Myoblast sheets (TCD-51073). METHODS AND RESULTS: In 3 study sites, we enrolled 7 patients with severe chronic HF due to ischemic heart disease despite maximal therapy, all of whom underwent transplantation of TCD-51073. No serious arrhythmia was reported, and no changes were noted in the frequency of ventricular extrasystole frequency. The primary efficacy endpoint of the change in left ventricular ejection fraction (LVEF) on gated blood-pool scintigraphy at 26 weeks after transplantation showed that 5 subjects were responders (classified as "improved" or "unchanged"). In addition, LVEF on echocardiography improved over time, with a change in LVEF of 7.1±2.8% at 26 weeks posttransplantation. Among the 7 subjects, 6 showed improvement in New York Heart Association functional class by at least 1 class. The 6-min walk distance was 410.1±136.1 m before transplantation and 455.4±103.7 m at 26 weeks after transplantation. CONCLUSIONS: This study demonstrated the feasibility and safety of the transplantation of TCD-51073 in the patients with severe chronic HF due to ischemic heart disease, suggesting that TCD-51073 might maintain or improve cardiac function, symptoms, and physical function.