The Experts below are selected from a list of 227001 Experts worldwide ranked by ideXlab platform
Shirin Bonni - One of the best experts on this subject based on the ideXlab platform.
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PIAS1 and TIF1γ collaborate to promote SnoN SUMOylation and suppression of epithelial–mesenchymal transition
Cell Death & Differentiation, 2020Co-Authors: Ayan Chanda, Yoshiho Ikeuchi, Kunal Karve, Anusi Sarkar, Lili Deng, Amrita Singh Chandhoke, Azad Bonni, Shirin BonniAbstract:SUMO E3 ligases specify protein substrates for SUMOylation. The SUMO E3 ligases PIAS1 and TIF1γ target the transcriptional regulator SnoN for SUMOylation leading to suppression of epithelial–mesenchymal transition (EMT). Whether and how TIF1γ and PIAS1 might coordinate SnoN SUMOylation and regulation of EMT remained unknown. Here, we reveal that SnoN associates simultaneously with both TIF1γ and PIAS1, leading to a trimeric protein complex. Hence, PIAS1 and TIF1γ collaborate to promote the SUMOylation of SnoN. Importantly, loss of function studies of PIAS1 and TIF1γ suggest that these E3 ligases act in an interdependent manner to suppress EMT of breast cell-Derived Tissue organoids. Collectively, our findings unveil a novel mechanism by which SUMO E3 ligases coordinate substrate SUMOylation with biological implications.
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PIAS1 and TIF1γ collaborate to promote SnoN SUMOylation and suppression of epithelial–mesenchymal transition
Cell Death & Differentiation, 2020Co-Authors: Ayan Chanda, Yoshiho Ikeuchi, Kunal Karve, Anusi Sarkar, Lili Deng, Amrita Singh Chandhoke, Azad Bonni, Shirin BonniAbstract:SUMO E3 ligases specify protein substrates for SUMOylation. The SUMO E3 ligases PIAS1 and TIF1γ target the transcriptional regulator SnoN for SUMOylation leading to suppression of epithelial–mesenchymal transition (EMT). Whether and how TIF1γ and PIAS1 might coordinate SnoN SUMOylation and regulation of EMT remained unknown. Here, we reveal that SnoN associates simultaneously with both TIF1γ and PIAS1, leading to a trimeric protein complex. Hence, PIAS1 and TIF1γ collaborate to promote the SUMOylation of SnoN. Importantly, loss of function studies of PIAS1 and TIF1γ suggest that these E3 ligases act in an interdependent manner to suppress EMT of breast cell-Derived Tissue organoids. Collectively, our findings unveil a novel mechanism by which SUMO E3 ligases coordinate substrate SUMOylation with biological implications.
Simon P. Hoerstrup - One of the best experts on this subject based on the ideXlab platform.
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Adipose Derived Tissue engineered heart valve
Journal of Tissue Science & Engineering, 2015Co-Authors: Laura Frese, Bart Sanders, Gertrude M. Beer, Benedikt Weber, A. Driessen Mol, F.p.t. Baaijens, Simon P. HoerstrupAbstract:Abstract Introduction: A major challenge associated with heart valve Tissue engineering is the in vitro creation of mature Tissue structures compliant with native valve functionality. Various cell types have been investigated for heart valve Tissue engineering. In addition to prenatal, umbilical cord- and vascular-Derived cells, mesenchymal stem cells (MSCs) have gained large interest for Tissue engineering purposes, because of their broad differentiation potential. However, bone marrow Derived MSCs require a highly invasive harvesting procedure and decline in both cell number and differentiation potential proportionally with the donor’s age. In contrast, adipose Derived stem cells (ADSCs) represent an interesting alternative. The ease of repeated access to subcutaneous adipose Tissue as well as the less invasive donation procedures provide clear advantages. Therefore, this study investigated the suitability of ADSCs as alternative cell source for Tissue engineered heart valves (TEHVs). Methods: Human ADSCs were seeded on TEHV-scaffolds (n=11) made of nonwoven polyglycolic acid coated with poly-4-hydroxybutyrate. TEHVs were cultivated in diastolic-pulse-duplicator-bioreactor systems and subsequently seeded with a superficial layer of ADSC-Derived endothelial cells. Quantitative assessment of extracellular matrix composition of the TEHV-leaflets was performed with biochemical analyses for sulphated glycosaminoglycans, hydroxyproline and DNA content. Microstructural evaluation was performed on representative samples of the TEHVleaflets by (immuno-)histochemistry and scanning electron microscopy. The mechanical properties of the ADSC Derived TEHV-leaflets were characterized by biaxial tensile tests. Results: ADSC-Derived TEHV-leaflets showed a homogenous vital cell distribution throughout the whole leaflet structure that consisted of large amounts of glycosaminoglycans and collagen and was endothelialized. Furthermore, the mechanically stable matrix of the ADSC-Derived TEHVs showed a stiffness range in the right order of magnitude for heart valve applications. Conclusion: Human ADSCs represent a promising alternative autologous mesenchymal cell source for TEHVs that is of large clinical relevance due to their easy accessibility, efficient proliferation and excellent Tissue formation capacities.
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Stem cells for heart valve regeneration
Swiss Medical Weekly, 2012Co-Authors: Benedikt Weber, Maximilian Y. Emmert, Simon P. HoerstrupAbstract:Heart valve Tissue engineering holds the potential to overcome limitations of currently used heart valve prostheses. It involves the isolation and expansion of autologous patient cells, the subsequent seeding of these cells onto an appropriate scaffold material, the in vitro incubation and the in vivo implantation of the Derived Tissue-engineered construct into the patient from whom the cells were taken. While vascular-Derived cells require harvest of intact donor Tissue and show limited expansion capacities, the use of stem or progenitor cells may overcome these limitations and expand the versatility of the concept of heart valve Tissue engineering. Possible sources include cells isolated from blood, bone marrow, adipose Tissue, amniotic fluid, chorionic villi, umbilical cord and induced pluripotent stem cells. Here we review different stem cell sources with particular regard to cellular phenotypes and their suitability for application in heart valve Tissue engineering.
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Adipose Fat Derived Tissue-Engineered Heart Valves
QScience Proceedings, 2012Co-Authors: Laura Frese, Petra E. Dijkman, Bart Sanders, Gertrude M. Beer, Benedikt Weber, F.p.t. Baaijens, Maximilian Y. Emmert, Chad Brokopp, Anita Anita Driessen-mol, Simon P. HoerstrupAbstract:Abstract A major challenge in Tissue engineering of heart valves is the in vitro creation of mature Tissue structures compliant with the native valve function. Concerning the remodeling capacity of the extracellular matrix (ECM), various cell types have been investigated, including prenatal cells, umbilical cord and vascular Derived cells. The pluripotency and availability of human mesenchymal stem cells has made them highly attractive for Tissue engineering purposes. However, for clinical use, adult bone marrow Derived mesenchymal stem cells (MSC) are suboptimal due to the highly invasive donation procedure, and the decline in MSC number and differentiation potential with increasing age of the patient. Adipose Derived stem cells (ADSC) represent an interesting alternative of mesodermal origin. The easy and repeatable access to subcutaneous adipose Tissue and the simple isolation procedures provide a clear advantage. Here, we investigate the suitability of ADSC as a novel cell source for Tissue engineered heart valves (TEHV). Tissue Engineered (TE) heart valve leaflets (n=6) were produced, based on PGA/P4HB scaffolds seeded with human ADSC isolated from fat Tissue excisions from plastic surgery. To stimulate Tissue formation and induce matrix alignment, the TE leaflets were cultivated in dynamic strain bioreactors for 4 weeks. We subsequently reseeded the cultivated valves with ADSC Derived endothelial cells. Differentiation into endothelial-like cells was induced by cultivation of ADSC in the presence of vascular endothelial growth factor. To determine the ECM composition of the TE leaflets, biochemical analyses for glycosaminoglycans (GAG), hydroxyproline (HYP) and DNA were performed. To further evaluate the microstructural features, Tissue samples of TE leaflets were analyzed by stainings as well as by scanning electron microscopy. The mechanical properties of the ADSC Derived TE leaflets were analyzed using a biaxial tensile tester. TE leaflets based on ADSC showed a homogenous vital cell distribution throughout the whole leaflet structure and the formation of a confluent endothelial lining. Furthermore, a mechanically stable matrix with GAG and collagen was demonstrated. These results indicate that ADSC represent an interesting alternative autologous mesenchymal human cell source with clinical relevance due to their easy accessibility and excellent proliferation and Tissue formation capacities.
Mareike Sauer - One of the best experts on this subject based on the ideXlab platform.
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Human cell-Derived Tissue-engineered heart valve with integrated Valsalva sinuses: towards native-like transcatheter pulmonary valve replacements
npj Regenerative Medicine, 2019Co-Authors: Sarah E. Motta, Matilde Putti, Héctor Rodriguez Cetina Biefer, Mareike Sauer, Emanuela S. Fioretta, Valentina Lintas, Petra E. Dijkman, Miriam Lipiski, Etem Caliskan, Nikola CesarovicAbstract:Transcatheter valve replacement indication is currently being extended to younger and lower-risk patients. However, transcatheter prostheses are still based on glutaraldehyde-fixed xenogeneic materials. Hence, they are prone to calcification and long-term structural degeneration, which are particularly accelerated in younger patients. Tissue-engineered heart valves based on decellularized in vitro grown Tissue-engineered matrices (TEM) have been suggested as a valid alternative to currently used bioprostheses, showing good performance and remodeling capacity as transcatheter pulmonary valve replacement (TPVR) in sheep. Here, we first describe the in vitro development of human cell-Derived TEM (hTEM) and their application as Tissue-engineered sinus valves (hTESVs), endowed with Valsalva sinuses for TPVR. The hTEM and hTESVs were systematically characterized in vitro by histology, immunofluorescence, and biochemical analyses, before they were evaluated in a pulse duplicator system under physiological pulmonary pressure conditions. Thereafter, transapical delivery of hTESVs was tested for feasibility and safety in a translational sheep model, achieving good valve performance and early cellular infiltration. This study demonstrates the principal feasibility of clinically relevant hTEM to manufacture hTESVs for TPVR.
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Development of a Novel Human Cell-Derived Tissue-Engineered Heart Valve for Transcatheter Aortic Valve Replacement: an In Vitro and In Vivo Feasibility Study
Journal of Cardiovascular Translational Research, 2018Co-Authors: Valentina Lintas, Marco Pensalfini, Emanuela S. Fioretta, Petra E. Dijkman, Miriam Lipiski, Sarah E. Motta, Etem Caliskan, Edoardo Mazza, H Rodriguez, Mareike SauerAbstract:Transcatheter aortic valve replacement (TAVR) is being extended to younger patients. However, TAVR-compatible bioprostheses are based on xenogeneic materials with limited durability. Off-the-shelf Tissue-engineered heart valves (TEHVs) with remodeling capacity may overcome the shortcomings of current TAVR devices. Here, we develop for the first time a TEHV for TAVR, based on human cell-Derived extracellular matrix and integrated into a state-of-the-art stent for TAVR. The TEHVs, characterized by a dense acellular collagenous matrix, demonstrated in vitro functionality under aortic pressure conditions (n = 4). Next, transapical TAVR feasibility and in vivo TEHV functionality were assessed in acute studies (n = 5) in sheep. The valves successfully coped with the aortic environment, showing normal leaflet motion, free coronary flow, and absence of stenosis or paravalvular leak. At explantation, TEHVs presented full structural integrity and initial cell infiltration. Its long-term performance proven, such TEHV could fulfill the need for next-generation lifelong TAVR prostheses.
Ayan Chanda - One of the best experts on this subject based on the ideXlab platform.
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PIAS1 and TIF1γ collaborate to promote SnoN SUMOylation and suppression of epithelial–mesenchymal transition
Cell Death & Differentiation, 2020Co-Authors: Ayan Chanda, Yoshiho Ikeuchi, Kunal Karve, Anusi Sarkar, Lili Deng, Amrita Singh Chandhoke, Azad Bonni, Shirin BonniAbstract:SUMO E3 ligases specify protein substrates for SUMOylation. The SUMO E3 ligases PIAS1 and TIF1γ target the transcriptional regulator SnoN for SUMOylation leading to suppression of epithelial–mesenchymal transition (EMT). Whether and how TIF1γ and PIAS1 might coordinate SnoN SUMOylation and regulation of EMT remained unknown. Here, we reveal that SnoN associates simultaneously with both TIF1γ and PIAS1, leading to a trimeric protein complex. Hence, PIAS1 and TIF1γ collaborate to promote the SUMOylation of SnoN. Importantly, loss of function studies of PIAS1 and TIF1γ suggest that these E3 ligases act in an interdependent manner to suppress EMT of breast cell-Derived Tissue organoids. Collectively, our findings unveil a novel mechanism by which SUMO E3 ligases coordinate substrate SUMOylation with biological implications.
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PIAS1 and TIF1γ collaborate to promote SnoN SUMOylation and suppression of epithelial–mesenchymal transition
Cell Death & Differentiation, 2020Co-Authors: Ayan Chanda, Yoshiho Ikeuchi, Kunal Karve, Anusi Sarkar, Lili Deng, Amrita Singh Chandhoke, Azad Bonni, Shirin BonniAbstract:SUMO E3 ligases specify protein substrates for SUMOylation. The SUMO E3 ligases PIAS1 and TIF1γ target the transcriptional regulator SnoN for SUMOylation leading to suppression of epithelial–mesenchymal transition (EMT). Whether and how TIF1γ and PIAS1 might coordinate SnoN SUMOylation and regulation of EMT remained unknown. Here, we reveal that SnoN associates simultaneously with both TIF1γ and PIAS1, leading to a trimeric protein complex. Hence, PIAS1 and TIF1γ collaborate to promote the SUMOylation of SnoN. Importantly, loss of function studies of PIAS1 and TIF1γ suggest that these E3 ligases act in an interdependent manner to suppress EMT of breast cell-Derived Tissue organoids. Collectively, our findings unveil a novel mechanism by which SUMO E3 ligases coordinate substrate SUMOylation with biological implications.
Sarah E. Motta - One of the best experts on this subject based on the ideXlab platform.
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Human cell-Derived Tissue-engineered heart valve with integrated Valsalva sinuses: towards native-like transcatheter pulmonary valve replacements
npj Regenerative Medicine, 2019Co-Authors: Sarah E. Motta, Matilde Putti, Héctor Rodriguez Cetina Biefer, Mareike Sauer, Emanuela S. Fioretta, Valentina Lintas, Petra E. Dijkman, Miriam Lipiski, Etem Caliskan, Nikola CesarovicAbstract:Transcatheter valve replacement indication is currently being extended to younger and lower-risk patients. However, transcatheter prostheses are still based on glutaraldehyde-fixed xenogeneic materials. Hence, they are prone to calcification and long-term structural degeneration, which are particularly accelerated in younger patients. Tissue-engineered heart valves based on decellularized in vitro grown Tissue-engineered matrices (TEM) have been suggested as a valid alternative to currently used bioprostheses, showing good performance and remodeling capacity as transcatheter pulmonary valve replacement (TPVR) in sheep. Here, we first describe the in vitro development of human cell-Derived TEM (hTEM) and their application as Tissue-engineered sinus valves (hTESVs), endowed with Valsalva sinuses for TPVR. The hTEM and hTESVs were systematically characterized in vitro by histology, immunofluorescence, and biochemical analyses, before they were evaluated in a pulse duplicator system under physiological pulmonary pressure conditions. Thereafter, transapical delivery of hTESVs was tested for feasibility and safety in a translational sheep model, achieving good valve performance and early cellular infiltration. This study demonstrates the principal feasibility of clinically relevant hTEM to manufacture hTESVs for TPVR.
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Development of a Novel Human Cell-Derived Tissue-Engineered Heart Valve for Transcatheter Aortic Valve Replacement: an In Vitro and In Vivo Feasibility Study
Journal of Cardiovascular Translational Research, 2018Co-Authors: Valentina Lintas, Marco Pensalfini, Emanuela S. Fioretta, Petra E. Dijkman, Miriam Lipiski, Sarah E. Motta, Etem Caliskan, Edoardo Mazza, H Rodriguez, Mareike SauerAbstract:Transcatheter aortic valve replacement (TAVR) is being extended to younger patients. However, TAVR-compatible bioprostheses are based on xenogeneic materials with limited durability. Off-the-shelf Tissue-engineered heart valves (TEHVs) with remodeling capacity may overcome the shortcomings of current TAVR devices. Here, we develop for the first time a TEHV for TAVR, based on human cell-Derived extracellular matrix and integrated into a state-of-the-art stent for TAVR. The TEHVs, characterized by a dense acellular collagenous matrix, demonstrated in vitro functionality under aortic pressure conditions (n = 4). Next, transapical TAVR feasibility and in vivo TEHV functionality were assessed in acute studies (n = 5) in sheep. The valves successfully coped with the aortic environment, showing normal leaflet motion, free coronary flow, and absence of stenosis or paravalvular leak. At explantation, TEHVs presented full structural integrity and initial cell infiltration. Its long-term performance proven, such TEHV could fulfill the need for next-generation lifelong TAVR prostheses.