The Experts below are selected from a list of 384 Experts worldwide ranked by ideXlab platform

Ray C.-j. Chiu - One of the best experts on this subject based on the ideXlab platform.

  • Systemic and Coronary Delivery of Marrow Stromal Cells for Cellular Cardiomyoplasty: Advantages and Precautions
    2014
    Co-Authors: Brett S. Burstein, Dominique Shum-tim, Ray C.-j. Chiu
    Abstract:

    Implanting multipotent adult stem cells and progenitor cells is undergoing extensive laboratory studies as well as early clinical trials. In most of these studies, localized myocardial infarcts had been the target lesion, and donor cells had been implanted by local injections. However in heart failure due to diffuse cardiomyopathies, coronary or systemic delivery of donor cells may be preferable. The advantages and feasibility of such cell delivery techniques will be discussed, while possible risks associated with embolization by aggregated donor cells will be reported. With appropriate precautions, we believe such alternate delivery approaches would be clinically desirable in selected patients. Key words: administration, adult stem cells, aggregation, Cellular Cardiomyoplasty, embolism, marrow stromal cells. Basic Appl Myol 13 (1): 7-10, 2003 Cell therapy to regenerate damaged myocardium, or “Cellular Cardiomyoplasty ” [5], is undergoing active experimental studies [10, 14, 16, 19] and early clinical trial

  • placental mesenchymal stem cells a unique source for Cellular Cardiomyoplasty
    The Annals of Thoracic Surgery, 2013
    Co-Authors: Georges Makhoul, Ray C.-j. Chiu, Renzo Cecere
    Abstract:

    In coronary heart disease, the use of stem cells for regeneration purposes has been broadly studied. Whereas bone marrow mesenchymal stem cells remain the most extensively investigated, other cell sources have been reported. Here we discuss and compare the characteristics of placenta-derived mesenchymal stem cells as a novel alternative cell source for Cellular Cardiomyoplasty. These cells are isolated from the human term placenta, which is normally discarded post partum. With their lack of ethical conflicts and young age, the readily available placenta-derived mesenchymal stem cells could be more suitable for myocardial regenerative therapy.

  • marrow stromal cells for cell based therapy the role of antiinflammatory cytokines in Cellular Cardiomyoplasty
    The Annals of Thoracic Surgery, 2010
    Co-Authors: Guangyong Chen, Ray C.-j. Chiu, Madhur Nayan, Minh Duong, Juan Francisco Asenjo, Dominique Shumtim
    Abstract:

    Background The mechanism by which marrow stromal cells (MSCs) improve cardiac function after myocardial infarction (MI) is still unclear. Because MI patients with lower circulating proinflammatory/antiinflammatory cytokine ratios have been reported to have a better prognosis and in vitro studies showed that MSCs express antiinflammatory cytokines, we hypothesized that changes in cytokine ratios in the infarct microenvironment after MSC therapy may play a role in improving early cardiac function after MI. Methods Sixty-three rats that survived left coronary artery ligations were injected with culture media (group M) or MSCs (group C). Cardiac functional changes were assessed with echocardiography. Cytokine gene expressions of interleukin (IL)-1β, IL-6, IL-8, (proinflammatory) and IL-10 (antiinflammatory) were quantified by real-time polymerase chain reaction. ExtraCellular matrix deposition, injury score, and the matrix metallopeptidase 2/tissue inhibitor of metallopeptidase 1 ratio were also analyzed. Results The ratio of proinflammatory/antiinflammatory cytokine gene expression was decreased in group C at various times, particularly in the early postoperative period. In group C, the matrix metallopeptidase 2/tissue inhibitor of metallopeptidase 1 gene expression ratio was significantly lower than group M at the early phase (12 hours), which in group C was translated into significantly lower extraCellular matrix deposition at 24 hours, 1, and 2 weeks. Functional recovery was also significantly better in cell therapy group C. Conclusions Our data demonstrate that MSC therapy decreases the proinflammatory/antiinflammatory cytokine ratio in the microenvironment early after MI. This is associated with subsequent less scar formation and improved cardiac function.

  • MSC Immune Tolerance in Cellular Cardiomyoplasty
    Seminars in thoracic and cardiovascular surgery, 2008
    Co-Authors: Ray C.-j. Chiu
    Abstract:

    During the past several years, there have been increasing experimental and early clinical observations indicating that allogeneic, and even xenogeneic, mesenchymal stem cells (MSCs) may be useful for Cellular Cardiomyoplasty. Although the immune tolerance of MSCs is well established in various in vitro studies, controversies on the in vivo immune tolerance of MSCs persist. Confirmation of the feasibility of allogeneic Cellular Cardiomyoplasty will have vast clinical implications, since it will provide convenient "off-the-shelf" donor cells, as a vehicle for gene therapy, and avoid the need to use dysfunctional autologous MSCs in senile and/or disabled patients.

  • Cellular Cardiomyoplasty routes of cell delivery and retention
    Frontiers in Bioscience, 2008
    Co-Authors: Adil Al H Kindi, Dominique Shumtim, Ray C.-j. Chiu
    Abstract:

    Experimental and clinical studies have proven the feasibility of Cellular Cardiomyoplasty in treating the damaged myocardium following ischemic injury. Over the years, this field has exploded with different investigators trying different routes of cell delivery ranging from direct cell injection into the heart to peripheral intravenous delivery utilizing the various signaling mechanisms known. These different routes have resulted in a wide range of retention and engraftment of cells in the target tissues. In this review, we will explore the different modalities of cell delivery, the pros and cons of each route and the Cellular retention and therapeutic efficacy of these routes. We will then look into the different theories that try to explain the observed retention and engraftment of cells in the target tissues. Finally, we will discuss various methods that can improve Cellular retention and engraftment and hence better improvement in myocardial function.

Hsingwen Sung - One of the best experts on this subject based on the ideXlab platform.

  • intramuscular delivery of 3d aggregates of huvecs and cbmscs for Cellular Cardiomyoplasty in rats with myocardial infarction
    Journal of Controlled Release, 2013
    Co-Authors: Dingyuan Chen, Chiehcheng Huang, Haoji Wei, Weiwen Lin, Shiawmin Hwang, Kunju Lin, Yen Chang, Hsingwen Sung
    Abstract:

    Cell-based therapeutic neovascularization is a promising method for treating ischemic disorders. In this work, human umbilical vein endothelial cells (HUVECs) were thoroughly premixed with cord-blood mesenchymal stem cells (cbMSCs) and cultivated to form three-dimensional (3D) cell aggregates for Cellular Cardiomyoplasty. In the in vitro study, tubular networks were formed at day 1 after the co-culturing of dissociated HUVECs and cbMSCs on Matrigel; however, as time progressed, the grown tubular networks regressed severely. Conversely, when 3D cell aggregates were grown on Matrigel, mature and stable tubular networks were observed over time, under the influence of their intensive cell-extraCellular matrix (ECM) interactions and cell-cell contacts. 3D cell aggregates were transplanted into the peri-infarct zones of rats with myocardial infarction (MI) via direct intramyocardial injection. Based on our pinhole single photon emission computed tomography (SPECT) myocardial-perfusion observations, echocardiographic heart-function examinations and histological analyses, the engrafted 3D cell aggregates considerably enhanced the vascular densities and the blood flow recovery in the ischemic myocardium over those of their dissociated counterparts, thereby reducing the size of perfusion defects and restoring cardiac function. These results demonstrate that the intramuscular delivery of 3D cell aggregates of HUVECs/cbMSCs can be a valuable cell-based regenerative therapeutic strategy against MI.

  • a translational approach in using cell sheet fragments of autologous bone marrow derived mesenchymal stem cells for Cellular Cardiomyoplasty in a porcine model
    Biomaterials, 2013
    Co-Authors: Chiehcheng Huang, Weiwen Lin, Shiawmin Hwang, Dingyuan Chen, Yen Chang, Hungwen Tsai, Wenyu Lee, Yiwen Hung, Jeewei Chen, Hsingwen Sung
    Abstract:

    Based on a porcine model with surgically created myocardial infarction (MI) as a pre-clinical scheme, this study investigates the clinical translation of cell sheet fragments of autologous mesenchymal stem cells (MSCs) for Cellular Cardiomyoplasty. MSC sheet fragments retaining endogenous extraCellular matrices are fabricated using a thermo-responsive methylcellulose hydrogel system. Echocardiographic observations indicate that transplantation of MSC sheet fragments in infarcted hearts can markedly attenuate the adverse ventricular dilation and preserve the cardiac function post MI, which is in contrast to the controlled groups receiving saline or dissociated MSCs. Additionally, histological analyses suggest that administering MSC sheet fragments significantly prevents the scar expansion and left ventricle remodeling after MI. Immunohistochemistry results demonstrate that the engrafted MSCs can differentiate into endothelial cells and smooth muscle cells, implying that angiogenesis and the subsequent regional perfusion improvement is a promising mechanism for ameliorating post-infarcted cardiac function. However, according to the data recorded by an implantable loop recorder, the transplanted MSCs may provoke arrhythmia. Nevertheless, the proposed approach may potentially lead to the eventual translation of MSC-based therapy into practical and effective clinical treatments.

  • enhancement of cell retention and functional benefits in myocardial infarction using human amniotic fluid stem cell bodies enriched with endogenous ecm
    Biomaterials, 2011
    Co-Authors: Shiawmin Hwang, Jiunjie Wang, Yen Chang, Mingsong Tsai, Hsingwen Sung
    Abstract:

    Stem cell transplantation may repair the infarcted heart. Despite the encouraging preliminary results, an optimal cell type used and low retention of the transplanted cells remain to be overcome. In this study, a multiwelled methylcellulose hydrogel system was used to cultivate human amniotic-fluid stem cells (hAFSCs) to form spherically symmetric cell bodies for Cellular Cardiomyoplasty. The grown hAFSC bodies enriched with extraCellular matrices (ECM) were xenogenically transplanted in the peri-infarct area of an immune-suppressed rat, via direct intramyocardial injection. Results of bioluminescence imaging and real-time PCR revealed that hAFSC bodies could considerably enhance cell retention and engraftment in short-term and long-term observations, when compared with dissociated hAFSCs. Echocardiography and magnetic resonance imaging showed that the enhanced cell engraftment in the hAFSC-body group could significantly attenuate the progression of heart failure, improve the global function, and increase the regional wall motion. At the infarct, expressions of HGF, bFGF and VEGF were significantly up-regulated, an indication of the significantly increased vessel densities in the hearts treated with hAFSC bodies. The injected hAFSC bodies could undergo differentiation into angiogenic and cardiomyogenic lineages and contribute to functional benefits by direct regeneration. The aforementioned results demonstrate that hAFSC bodies can attenuate cell loss after intramuscular injection by providing an adequate physical size and offering an enriched ECM environment to retain the transplanted cells in the myocardium, thus improving heart function.

  • Cellular Cardiomyoplasty with human amniotic fluid stem cells in vitro and in vivo studies
    Tissue Engineering Part A, 2010
    Co-Authors: Yichun Yeh, Haoji Wei, Shiawmin Hwang, Yen Chang, Wenyu Lee, Liwen Hsu, Minfan Chung, Mingsong Tsai, Hsingwen Sung
    Abstract:

    Human amniotic fluid stem cells (hAFSCs) derived from second-trimester amniocentesis were evaluated for the therapeutic potential of cardiac repair. Whether hAFSCs can be differentiated into cardiomyogenic cells and toward the maturation of endothelial cell lineage was investigated in vitro using mimicking differentiation milieu. Employing an immune-suppressed rat model with experimental myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were three treatment groups: sham, saline, and hAFSCs (n ≥ 10). When cultured with rat neonatal cardiomyocytes or in endothelial growth medium-2 enriched with vascular endothelial growth factor, hAFSCs were differentiated into cardiomyocyte-like cells and cells of endothelial lineage, respectively. After 4 weeks, hAFSC-treated animals showed a preservation of the infarcted thickness, an attenuation of left ventricle remodeling, a higher vascular density, and thus an improvement in cardiac function, w...

  • spherically symmetric mesenchymal stromal cell bodies inherent with endogenous extraCellular matrices for Cellular Cardiomyoplasty
    Stem Cells, 2009
    Co-Authors: Chungchi Wang, Weiwen Lin, Shiawmin Hwang, Yen Chang, Wenyu Lee, Chunhung Chen, Chihhao Huang, Hsingwen Sung
    Abstract:

    Cell transplantation via direct intramyocardial injection is a promising therapy for patients with myocardial infarction; however, retention of the transplanted cells at the injection sites remains a central issue following injection of dissociated cells. Using a thermoresponsive hydrogel system with a multiwell structure, we successfully developed an efficient technique to generate spherically symmetric bodies of mesenchymal stromal cells (MSCs) inherent with endogenous extraCellular matrices (ECMs) for direct intramyocardial injection. After injection through a needle and upon transferring to another growth surface, the time required to attach, migrate, and proliferate was significantly shorter for the MSC bodies than the dissociated MSCs. Employing a syngeneic rat model with experimental myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were four treatment groups (n = 10): sham, phosphate-buffered saline, dissociated MSCs, and MSC bodies. The results obtained in the echocardiography and catheterization measurements demonstrated that the MSC body group had a superior heart function to the dissociated MSC group. Histologically, it was found that MSC bodies could provide an adequate physical size to entrap into the interstices of muscular tissues and offer a favorable ECM environment to retain the transplanted cells intramuscularly. Additionally, transplantation of MSC bodies stimulated a significant increase in vascular density, thus improving the cardiac function. These results indicated that the spherically symmetric bodies of MSCs developed in the study may serve as a cell-delivery vehicle and improve the efficacy of therapeutic cell transplantation.

Shiawmin Hwang - One of the best experts on this subject based on the ideXlab platform.

  • intramuscular delivery of 3d aggregates of huvecs and cbmscs for Cellular Cardiomyoplasty in rats with myocardial infarction
    Journal of Controlled Release, 2013
    Co-Authors: Dingyuan Chen, Chiehcheng Huang, Haoji Wei, Weiwen Lin, Shiawmin Hwang, Kunju Lin, Yen Chang, Hsingwen Sung
    Abstract:

    Cell-based therapeutic neovascularization is a promising method for treating ischemic disorders. In this work, human umbilical vein endothelial cells (HUVECs) were thoroughly premixed with cord-blood mesenchymal stem cells (cbMSCs) and cultivated to form three-dimensional (3D) cell aggregates for Cellular Cardiomyoplasty. In the in vitro study, tubular networks were formed at day 1 after the co-culturing of dissociated HUVECs and cbMSCs on Matrigel; however, as time progressed, the grown tubular networks regressed severely. Conversely, when 3D cell aggregates were grown on Matrigel, mature and stable tubular networks were observed over time, under the influence of their intensive cell-extraCellular matrix (ECM) interactions and cell-cell contacts. 3D cell aggregates were transplanted into the peri-infarct zones of rats with myocardial infarction (MI) via direct intramyocardial injection. Based on our pinhole single photon emission computed tomography (SPECT) myocardial-perfusion observations, echocardiographic heart-function examinations and histological analyses, the engrafted 3D cell aggregates considerably enhanced the vascular densities and the blood flow recovery in the ischemic myocardium over those of their dissociated counterparts, thereby reducing the size of perfusion defects and restoring cardiac function. These results demonstrate that the intramuscular delivery of 3D cell aggregates of HUVECs/cbMSCs can be a valuable cell-based regenerative therapeutic strategy against MI.

  • a translational approach in using cell sheet fragments of autologous bone marrow derived mesenchymal stem cells for Cellular Cardiomyoplasty in a porcine model
    Biomaterials, 2013
    Co-Authors: Chiehcheng Huang, Weiwen Lin, Shiawmin Hwang, Dingyuan Chen, Yen Chang, Hungwen Tsai, Wenyu Lee, Yiwen Hung, Jeewei Chen, Hsingwen Sung
    Abstract:

    Based on a porcine model with surgically created myocardial infarction (MI) as a pre-clinical scheme, this study investigates the clinical translation of cell sheet fragments of autologous mesenchymal stem cells (MSCs) for Cellular Cardiomyoplasty. MSC sheet fragments retaining endogenous extraCellular matrices are fabricated using a thermo-responsive methylcellulose hydrogel system. Echocardiographic observations indicate that transplantation of MSC sheet fragments in infarcted hearts can markedly attenuate the adverse ventricular dilation and preserve the cardiac function post MI, which is in contrast to the controlled groups receiving saline or dissociated MSCs. Additionally, histological analyses suggest that administering MSC sheet fragments significantly prevents the scar expansion and left ventricle remodeling after MI. Immunohistochemistry results demonstrate that the engrafted MSCs can differentiate into endothelial cells and smooth muscle cells, implying that angiogenesis and the subsequent regional perfusion improvement is a promising mechanism for ameliorating post-infarcted cardiac function. However, according to the data recorded by an implantable loop recorder, the transplanted MSCs may provoke arrhythmia. Nevertheless, the proposed approach may potentially lead to the eventual translation of MSC-based therapy into practical and effective clinical treatments.

  • injectable plga porous beads Cellularized by hafscs for Cellular Cardiomyoplasty
    Biomaterials, 2012
    Co-Authors: Chiehcheng Huang, Haoji Wei, Yichun Yeh, Jiunjie Wang, Weiwen Lin, Tingyin Lee, Shiawmin Hwang, Sungwook Choi, Younan Xia
    Abstract:

    Cellular Cardiomyoplasty has been limited by poor graft retention after cell transplantation. To ensure good retention of the engrafted cells, a microfluidic device was used to fabricate spherical porous beads of poly(D,L-lactic-co-glycolic acid) as a platform for cell delivery. The beads thus obtained had a relatively uniform size, a highly porous structure, and a favorably interconnected interior architecture, to facilitate the transportation of oxygen and nutrients. These porous beads were loaded with human amniotic fluid stem cells (hAFSCs) to generate Cellularized microscaffolds. Live/dead assay demonstrated that most of the cells in the porous constructs were viable. The hAFSCs that were grown in beads formed a complex three-dimensional organization with well-preserved extraCellular matrices (ECM) according to their porous structure. Retention of the administered beads was clearly identified at the site of engraftment following an experimentally induced myocardial infarction in a rat model. The results of echocardiography, magnetic resonance imaging, and histological analyses suggest that the transplantation of hAFSC beads into an infarcted heart could effectively maintain its gross morphology, prevent successive ventricular expansion, and thereby improve the post-infarcted cardiac function. Immunofluorescent staining revealed that the microenvironment that was provided by the infarcted myocardium might offer cues for the induction of the engrafted hAFSCs into angiogenic and cardiomyogenic lineages. Our results demonstrate that the Cellularized beads with endogenously secreted ECM were of sufficient physical size to be entrapped in the interstitial tissues following transplantation, thereby benefiting the infarcted heart.

  • enhancement of cell retention and functional benefits in myocardial infarction using human amniotic fluid stem cell bodies enriched with endogenous ecm
    Biomaterials, 2011
    Co-Authors: Shiawmin Hwang, Jiunjie Wang, Yen Chang, Mingsong Tsai, Hsingwen Sung
    Abstract:

    Stem cell transplantation may repair the infarcted heart. Despite the encouraging preliminary results, an optimal cell type used and low retention of the transplanted cells remain to be overcome. In this study, a multiwelled methylcellulose hydrogel system was used to cultivate human amniotic-fluid stem cells (hAFSCs) to form spherically symmetric cell bodies for Cellular Cardiomyoplasty. The grown hAFSC bodies enriched with extraCellular matrices (ECM) were xenogenically transplanted in the peri-infarct area of an immune-suppressed rat, via direct intramyocardial injection. Results of bioluminescence imaging and real-time PCR revealed that hAFSC bodies could considerably enhance cell retention and engraftment in short-term and long-term observations, when compared with dissociated hAFSCs. Echocardiography and magnetic resonance imaging showed that the enhanced cell engraftment in the hAFSC-body group could significantly attenuate the progression of heart failure, improve the global function, and increase the regional wall motion. At the infarct, expressions of HGF, bFGF and VEGF were significantly up-regulated, an indication of the significantly increased vessel densities in the hearts treated with hAFSC bodies. The injected hAFSC bodies could undergo differentiation into angiogenic and cardiomyogenic lineages and contribute to functional benefits by direct regeneration. The aforementioned results demonstrate that hAFSC bodies can attenuate cell loss after intramuscular injection by providing an adequate physical size and offering an enriched ECM environment to retain the transplanted cells in the myocardium, thus improving heart function.

  • Cellular Cardiomyoplasty with human amniotic fluid stem cells in vitro and in vivo studies
    Tissue Engineering Part A, 2010
    Co-Authors: Yichun Yeh, Haoji Wei, Shiawmin Hwang, Yen Chang, Wenyu Lee, Liwen Hsu, Minfan Chung, Mingsong Tsai, Hsingwen Sung
    Abstract:

    Human amniotic fluid stem cells (hAFSCs) derived from second-trimester amniocentesis were evaluated for the therapeutic potential of cardiac repair. Whether hAFSCs can be differentiated into cardiomyogenic cells and toward the maturation of endothelial cell lineage was investigated in vitro using mimicking differentiation milieu. Employing an immune-suppressed rat model with experimental myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were three treatment groups: sham, saline, and hAFSCs (n ≥ 10). When cultured with rat neonatal cardiomyocytes or in endothelial growth medium-2 enriched with vascular endothelial growth factor, hAFSCs were differentiated into cardiomyocyte-like cells and cells of endothelial lineage, respectively. After 4 weeks, hAFSC-treated animals showed a preservation of the infarcted thickness, an attenuation of left ventricle remodeling, a higher vascular density, and thus an improvement in cardiac function, w...

Eugen Kolossov - One of the best experts on this subject based on the ideXlab platform.

  • engraftment of engineered es cell derived cardiomyocytes but not bm cells restores contractile function to the infarcted myocardium
    Journal of Experimental Medicine, 2006
    Co-Authors: Eugen Kolossov, Wilhelm Roell, Philipp Sasse, Martin Breitbach, Toktam Bostani, Frank Pillekamp, Jens M Nygren, Olga Rubenchik, Jochen W U Fries, Daniela Wenzel
    Abstract:

    Cellular Cardiomyoplasty is an attractive option for the treatment of severe heart failure. It is, however, still unclear and controversial which is the most promising cell source. Therefore, we investigated and examined the fate and functional impact of bone marrow (BM) cells and embryonic stem cell (ES cell)-derived cardiomyocytes after transplantation into the infarcted mouse heart. This proved particularly challenging for the ES cells, as their enrichment into cardiomyocytes and their long-term engraftment and tumorigenicity are still poorly understood. We generated transgenic ES cells expressing puromycin resistance and enhanced green fluorescent protein cassettes under control of a cardiac-specific promoter. Puromycin selection resulted in a highly purified (>99%) cardiomyocyte population, and the yield of cardiomyocytes increased 6-10-fold because of induction of proliferation on purification. Long-term engraftment (4-5 months) was observed when co-transplanting selected ES cell-derived cardiomyocytes and fibroblasts into the injured heart of syngeneic mice, and no teratoma formation was found (n = 60). Although transplantation of ES cell-derived cardiomyocytes improved heart function, BM cells had no positive effects. Furthermore, no contribution of BM cells to cardiac, endothelial, or smooth muscle neogenesis was detected. Hence, our results demonstrate that ES-based cell therapy is a promising approach for the treatment of impaired myocardial function and provides better results than BM-derived cells.

  • engraftment of engineered es cell derived cardiomyocytes but not bm cells restores contractile function to the infarcted myocardium
    Journal of Experimental Medicine, 2006
    Co-Authors: Eugen Kolossov, Wilhelm Roell, Philipp Sasse, Martin Breitbach, Toktam Bostani, Frank Pillekamp, Jens M Nygren, Olga Rubenchik, Jochen W U Fries, Daniela Wenzel
    Abstract:

    Cellular Cardiomyoplasty is an attractive option for the treatment of severe heart failure. It is, however, still unclear and controversial which is the most promising cell source. Therefore, we investigated and examined the fate and functional impact of bone marrow (BM) cells and embryonic stem cell (ES cell)-derived cardiomyocytes after transplantation into the infarcted mouse heart. This proved particularly challenging for the ES cells, as their enrichment into cardiomyocytes and their long-term engraftment and tumorigenicity are still poorly understood. We generated transgenic ES cells expressing puromycin resistance and enhanced green fluorescent protein cassettes under control of a cardiac-specific promoter. Puromycin selection resulted in a highly purified (>99%) cardiomyocyte population, and the yield of cardiomyocytes increased 6-10-fold because of induction of proliferation on purification. Long-term engraftment (4-5 months) was observed when co-transplanting selected ES cell-derived cardiomyocytes and fibroblasts into the injured heart of syngeneic mice, and no teratoma formation was found (n = 60). Although transplantation of ES cell-derived cardiomyocytes improved heart function, BM cells had no positive effects. Furthermore, no contribution of BM cells to cardiac, endothelial, or smooth muscle neogenesis was detected. Hence, our results demonstrate that ES-based cell therapy is a promising approach for the treatment of impaired myocardial function and provides better results than BM-derived cells.

  • Cellular Cardiomyoplasty improves survival after myocardial injury
    Circulation, 2002
    Co-Authors: Wilhelm Roell, Ying Xia, Eva Stoecker, Wilhelm Bloch, Sharon Siedner, Klaus Tiemann, Michaela Fleischmann, Heribert Bohlen, Robert Stehle, Eugen Kolossov
    Abstract:

    Background— Cellular Cardiomyoplasty is discussed as an alternative therapeutic approach to heart failure. To date, however, the functional characteristics of the transplanted cells, their contribution to heart function, and most importantly, the potential therapeutic benefit of this treatment remain unclear. Methods and Results— Murine ventricular cardiomyocytes (E12.5–E15.5) labeled with enhanced green fluorescent protein (EGFP) were transplanted into the cryoinjured left ventricular walls of 2-month-old male mice. Ultrastructural analysis of the cryoinfarction showed a complete loss of cardiomyocytes within 2 days and fibrotic healing within 7 days after injury. Two weeks after operation, EGFP-positive cardiomyocytes were engrafted throughout the wall of the lesioned myocardium. Morphological studies showed differentiation and formation of interCellular contacts. Furthermore, electrophysiological experiments on isolated EGFP-positive cardiomyocytes showed time-dependent differentiation with postnatal v...

  • Cellular Cardiomyoplasty in a transgenic mouse model
    Transplantation, 2002
    Co-Authors: Wilhelm Roell, Yun Fan, Ying Xia, Eva Stoecker, Philipp Sasse, Eugen Kolossov, Wilhelm Bloch, Harald Metzner, Christoph Schmitz, Klaus Addicks
    Abstract:

    Background. Recent progress in the cardiotypic differentiation of embryonic and somatic stem cells opens novel prospects for the treatment of cardiovascular disorders. The aim of the present study was to develop a novel surgical approach that allows standardized Cellular Cardiomyoplasty in mouse with low-perioperative mortality. Methods. Reproducible transmural lesions were generated by cryoinjury followed by intramural injection of embryonic cardiomyocytes using a newly designed holding device and vital dye staining. This approach was validated with a transgenic mouse model, in which the live reporter gene-enhanced green fluorescent protein (EGFP) is under control of a cardiac-specific promoter. Results. The perioperative mortality was 10%. The engrafted EGFP-positive cardiomyocytes could be identified in a high percentage (72.2%, n=36) of operated animals. Conclusions. This novel approach enables reliable Cellular replacement therapy in mouse and greatly facilitates the analysis of its molecular, Cellular, and functional efficacy.

Yen Chang - One of the best experts on this subject based on the ideXlab platform.

  • intramuscular delivery of 3d aggregates of huvecs and cbmscs for Cellular Cardiomyoplasty in rats with myocardial infarction
    Journal of Controlled Release, 2013
    Co-Authors: Dingyuan Chen, Chiehcheng Huang, Haoji Wei, Weiwen Lin, Shiawmin Hwang, Kunju Lin, Yen Chang, Hsingwen Sung
    Abstract:

    Cell-based therapeutic neovascularization is a promising method for treating ischemic disorders. In this work, human umbilical vein endothelial cells (HUVECs) were thoroughly premixed with cord-blood mesenchymal stem cells (cbMSCs) and cultivated to form three-dimensional (3D) cell aggregates for Cellular Cardiomyoplasty. In the in vitro study, tubular networks were formed at day 1 after the co-culturing of dissociated HUVECs and cbMSCs on Matrigel; however, as time progressed, the grown tubular networks regressed severely. Conversely, when 3D cell aggregates were grown on Matrigel, mature and stable tubular networks were observed over time, under the influence of their intensive cell-extraCellular matrix (ECM) interactions and cell-cell contacts. 3D cell aggregates were transplanted into the peri-infarct zones of rats with myocardial infarction (MI) via direct intramyocardial injection. Based on our pinhole single photon emission computed tomography (SPECT) myocardial-perfusion observations, echocardiographic heart-function examinations and histological analyses, the engrafted 3D cell aggregates considerably enhanced the vascular densities and the blood flow recovery in the ischemic myocardium over those of their dissociated counterparts, thereby reducing the size of perfusion defects and restoring cardiac function. These results demonstrate that the intramuscular delivery of 3D cell aggregates of HUVECs/cbMSCs can be a valuable cell-based regenerative therapeutic strategy against MI.

  • a translational approach in using cell sheet fragments of autologous bone marrow derived mesenchymal stem cells for Cellular Cardiomyoplasty in a porcine model
    Biomaterials, 2013
    Co-Authors: Chiehcheng Huang, Weiwen Lin, Shiawmin Hwang, Dingyuan Chen, Yen Chang, Hungwen Tsai, Wenyu Lee, Yiwen Hung, Jeewei Chen, Hsingwen Sung
    Abstract:

    Based on a porcine model with surgically created myocardial infarction (MI) as a pre-clinical scheme, this study investigates the clinical translation of cell sheet fragments of autologous mesenchymal stem cells (MSCs) for Cellular Cardiomyoplasty. MSC sheet fragments retaining endogenous extraCellular matrices are fabricated using a thermo-responsive methylcellulose hydrogel system. Echocardiographic observations indicate that transplantation of MSC sheet fragments in infarcted hearts can markedly attenuate the adverse ventricular dilation and preserve the cardiac function post MI, which is in contrast to the controlled groups receiving saline or dissociated MSCs. Additionally, histological analyses suggest that administering MSC sheet fragments significantly prevents the scar expansion and left ventricle remodeling after MI. Immunohistochemistry results demonstrate that the engrafted MSCs can differentiate into endothelial cells and smooth muscle cells, implying that angiogenesis and the subsequent regional perfusion improvement is a promising mechanism for ameliorating post-infarcted cardiac function. However, according to the data recorded by an implantable loop recorder, the transplanted MSCs may provoke arrhythmia. Nevertheless, the proposed approach may potentially lead to the eventual translation of MSC-based therapy into practical and effective clinical treatments.

  • enhancement of cell retention and functional benefits in myocardial infarction using human amniotic fluid stem cell bodies enriched with endogenous ecm
    Biomaterials, 2011
    Co-Authors: Shiawmin Hwang, Jiunjie Wang, Yen Chang, Mingsong Tsai, Hsingwen Sung
    Abstract:

    Stem cell transplantation may repair the infarcted heart. Despite the encouraging preliminary results, an optimal cell type used and low retention of the transplanted cells remain to be overcome. In this study, a multiwelled methylcellulose hydrogel system was used to cultivate human amniotic-fluid stem cells (hAFSCs) to form spherically symmetric cell bodies for Cellular Cardiomyoplasty. The grown hAFSC bodies enriched with extraCellular matrices (ECM) were xenogenically transplanted in the peri-infarct area of an immune-suppressed rat, via direct intramyocardial injection. Results of bioluminescence imaging and real-time PCR revealed that hAFSC bodies could considerably enhance cell retention and engraftment in short-term and long-term observations, when compared with dissociated hAFSCs. Echocardiography and magnetic resonance imaging showed that the enhanced cell engraftment in the hAFSC-body group could significantly attenuate the progression of heart failure, improve the global function, and increase the regional wall motion. At the infarct, expressions of HGF, bFGF and VEGF were significantly up-regulated, an indication of the significantly increased vessel densities in the hearts treated with hAFSC bodies. The injected hAFSC bodies could undergo differentiation into angiogenic and cardiomyogenic lineages and contribute to functional benefits by direct regeneration. The aforementioned results demonstrate that hAFSC bodies can attenuate cell loss after intramuscular injection by providing an adequate physical size and offering an enriched ECM environment to retain the transplanted cells in the myocardium, thus improving heart function.

  • Cellular Cardiomyoplasty with human amniotic fluid stem cells in vitro and in vivo studies
    Tissue Engineering Part A, 2010
    Co-Authors: Yichun Yeh, Haoji Wei, Shiawmin Hwang, Yen Chang, Wenyu Lee, Liwen Hsu, Minfan Chung, Mingsong Tsai, Hsingwen Sung
    Abstract:

    Human amniotic fluid stem cells (hAFSCs) derived from second-trimester amniocentesis were evaluated for the therapeutic potential of cardiac repair. Whether hAFSCs can be differentiated into cardiomyogenic cells and toward the maturation of endothelial cell lineage was investigated in vitro using mimicking differentiation milieu. Employing an immune-suppressed rat model with experimental myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were three treatment groups: sham, saline, and hAFSCs (n ≥ 10). When cultured with rat neonatal cardiomyocytes or in endothelial growth medium-2 enriched with vascular endothelial growth factor, hAFSCs were differentiated into cardiomyocyte-like cells and cells of endothelial lineage, respectively. After 4 weeks, hAFSC-treated animals showed a preservation of the infarcted thickness, an attenuation of left ventricle remodeling, a higher vascular density, and thus an improvement in cardiac function, w...

  • spherically symmetric mesenchymal stromal cell bodies inherent with endogenous extraCellular matrices for Cellular Cardiomyoplasty
    Stem Cells, 2009
    Co-Authors: Chungchi Wang, Weiwen Lin, Shiawmin Hwang, Yen Chang, Wenyu Lee, Chunhung Chen, Chihhao Huang, Hsingwen Sung
    Abstract:

    Cell transplantation via direct intramyocardial injection is a promising therapy for patients with myocardial infarction; however, retention of the transplanted cells at the injection sites remains a central issue following injection of dissociated cells. Using a thermoresponsive hydrogel system with a multiwell structure, we successfully developed an efficient technique to generate spherically symmetric bodies of mesenchymal stromal cells (MSCs) inherent with endogenous extraCellular matrices (ECMs) for direct intramyocardial injection. After injection through a needle and upon transferring to another growth surface, the time required to attach, migrate, and proliferate was significantly shorter for the MSC bodies than the dissociated MSCs. Employing a syngeneic rat model with experimental myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were four treatment groups (n = 10): sham, phosphate-buffered saline, dissociated MSCs, and MSC bodies. The results obtained in the echocardiography and catheterization measurements demonstrated that the MSC body group had a superior heart function to the dissociated MSC group. Histologically, it was found that MSC bodies could provide an adequate physical size to entrap into the interstices of muscular tissues and offer a favorable ECM environment to retain the transplanted cells intramuscularly. Additionally, transplantation of MSC bodies stimulated a significant increase in vascular density, thus improving the cardiac function. These results indicated that the spherically symmetric bodies of MSCs developed in the study may serve as a cell-delivery vehicle and improve the efficacy of therapeutic cell transplantation.