Development of HLA engineered universal vascular grafts from human iPSCs
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ABSTRACT:
PROVIDER: PRJNA747546 | ENA |
REPOSITORIES: ENA
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Project description:Microtia, the congenital malformation of the external ear, imposes a significant psychosocial burden on affected children1-4. The current gold standard treatment, autologous costal cartilage reconstruction, requires multiple complex surgeries, including the harvest of rib cartilage5-7. Tissue engineering offers a promising alternative, enabling the generation of patient-specific auricular grafts from a small biopsy (~5 mg). However, despite multiple decades of research, clinically viable, tissue engineered auricular grafts remain unavailable8. Key challenges include fibrocartilage formation in vitro, heterogeneous extracellular matrix development, and mechanical inferiority, all resulting in graft deformation and degradation in vivo9-15. Here, we report the successful fabrication of bioprinted auricular grafts that closely resemble native human auricular cartilage. Our grafts demonstrated a uniform distribution of elastin, glycosaminoglycans, and collagen II, lacked collagen I, and achieved a compressive modulus of 803 ± 134 kPa after 9 weeks of maturation in vitro (human auricular cartilage: 1023 ± 101 kPa). In vivo, grafts maintained their structural integrity for 6 weeks in a subcutaneous rat model and showed a transition towards mature elastic fiber. These grafts represent the closest approximation to native elastic cartilage reported to date and lay the foundation for a clinically viable, long-term treatment for children affected by microtia.
2025-10-17 | GSE300497 | GEO
Project description:Tissue Engineered Elastic Cartilage-Mimetic Auricular Grafts for Microtia Reconstruction
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Project description:Human iPSCs and NSCs were engineered by AAVS1 and/or C13 safe-harbor TALENs which mediated targeted integration of various reporter genes at single or dual safe-harbor loci. Multiple clones of targeted human iPSCs were used to compare with parental untargeted NCRM5 iPSCs. Polyclonal targeted human NSCs were used to compare with their parental untargeted NCRM1NSCs or H9NSCs. Total RNA obtained from targeted human iPSCs or NSCs compared to untargeted control iPSCs or NSCs.
2014-09-01 | E-GEOD-55975 | biostudies-arrayexpress
Project description:Congenital and acquired esophageal pathologies such as oesophageal atresia can leave large tissue deficits in patients were insufficient oesophagus exists to restore continuity. Currently, these require replacement by repurposing the stomach, colon or small bowel. The aim of this study was to develop a tissue engineered oesophagus as an alternative, produced using a clinically relevant timescale, and determine feasibility, safety of autologous transplantation of autologous grafts via a thoracic approach in a growing minipig model, together with assessment of function and integration.
2025-12-23 | GSE280737 | GEO
Project description:Vascular smooth muscle cells (VSMCs) can be derived in large numbers from human induced pluripotent stem cells (hiPSCs) for producing tissue-engineered vascular grafts (TEVGs). However, hiPSC-derived TEVGs are hampered by low mechanical strength and significant radial dilation after implantation. Here, we report generation of hiPSC-derived TEVGs with mechanical strength comparable to native vessels used in arterial bypass grafts by utilizing biodegradable scaffolds, incremental pulsatile stretching, and optimal culture conditions. Following implantation into a rat aortic model, hiPSC-derived TEVGs show excellent patency without luminal dilation and effectively maintain mechanical and contractile function. This study provides a foundation for future production of non-immunogenic, cellularized hiPSC-derived TEVGs composed of allogenic vascular cells, potentially serving needs to a considerable number of patients whose dysfunctional vascular cells preclude TEVG generation via other methods.
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Project description:Human iPSCs and NSCs were engineered by AAVS1 and/or C13 safe-harbor TALENs which mediated targeted integration of various reporter genes at single or dual safe-harbor loci. Multiple clones of targeted human iPSCs were used to compare with parental untargeted NCRM5 iPSCs. Polyclonal targeted human NSCs were used to compare with their parental untargeted NCRM1NSCs or H9NSCs.
2014-09-01 | GSE55975 | GEO
Project description:Functional Integration of Autologous Tissue-Engineered Grafts in a Pre-Clinical Esophageal Defect Model
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Project description:Albeit vascular prostheses for the replacement of large arteries (e.g. aorta) are commercially available for decades, small-diameter vascular grafts (e.g., for coronary artery bypass graft surgery) still remain an unmet clinical need. Biostable polymers commonly used for the fabrication of aortic prostheses (e.g., poly(ethylene terephthalate) or expanded poly(tetrafluoroethylene)) have insufficient haemocompatibility to withstand thrombosis at low blood flow characteristic of small arteries (e.g., coronary artery). Hence, researchers endeavor to develop a biodegradable, tissue-engineered vascular graft (TEVG) to avoid the use of autologous blood vessels, such as saphenous vein or internal mammary artery, as conduits during the bypass surgery. Although a number of promising prototypes have been designed to date, none of them passed the pre-clinical trials successfully. Implantation into the ovine or porcine arteries is associated with thrombosis, neointimal hyperplasia, and aneurysms within one-year postoperation, precluding further clinical translation of TEVGs. Among the reasons of such impediment is that pathophysiology of TEVG implantation remains unclear and the molecular events occurring in the TEVG upon its implantation have not been properly investigated hitherto. Here, we for the first time performed a proteomic profiling of the TEVGs (n = 12) implanted into the ovine carotid arteries for one year and suffered from thrombosis to identify the signatures of TEVG failure in an unbiased manner. Contralateral intact ovine carotid arteries (n = 12) have been selected as a control group.
2022-11-26 | PXD036520 | Pride
Project description:We constructed a clinical-grade haplobank of 27 induced pluripotent stem cells (iPSCs) lines prepared in accordance with good manufacturing practice regulations from seven donors who were homozygous for one of the four most frequent human leukocyte antigen (HLA)-haplotypes in Japan. The haplobank could provide HLA-matched iPSCs lines to ~40% of the Japanese population. Since the first release in 2015, these iPSC lines have been used in more than 12 clinical studies. We performed rigorous quality control (QC) tests, including residual episomal vectors, genetic mutations in cancer-related genes, copy number alterations, karyotype, expression of markers of the undifferentiated state, morphology, identity (HLA typing and short tandem repeat analysis), sterility and endotoxin. Although the significance of most mutations in cancer-related genes is unknown, we excluded iPSC lines with such mutations to maximize the safety. The haplobank we have established here is an important step toward the clinical application of iPSCs in cell therapies.
2022-11-15 | GSE201468 | GEO