• Arterial tissue
• Cellular content
• Collagen
• Elastin
• Imaging
• Microscopy
• Microstructure

• Arteries/diagnostic imaging
• Humans
• Animals

• tissue engineered blood vessels
• tissue engineering
• vascular engineering
• vascular model disease
• vascular substitutes
• vascularization

• Tissue Engineering/methods
• Humans
• Blood Vessel Prosthesis
• Animals
• Tissue Scaffolds/chemistry
• Blood Vessels/cytology
• Biocompatible Materials/chemistry

• Endothelial cells
• Regenerative medicine
• Seed cells
• Vascular diseases
• Vascularization

• Humans
• Endothelial Cells/cytology
• Endothelial Cells/metabolism
• Animals
• Tissue Engineering/methods
• Cell Differentiation

• CQYC20210303360 Chongqing Talent Program
• Chongqing Talent Program

• decellularization
• endothelialization
• small‐diameter vascular grafts
• tissue engineering

• Tissue Engineering/methods
• Humans
• Animals
• Blood Vessel Prosthesis
• Decellularized Extracellular Matrix/chemistry
• Tissue Scaffolds/chemistry

• 82070277 National Natural Science Foundation of China
• 82170325 National Natural Science Foundation of China
• 2022YFS0610 Sichuan Province science and technology projects
• 2020LZXNYDF01 Technology Strategic Cooperation Programs of Luzhou Municipal People's Government and Southwest Medical University

• Biomaterials
• Cardiovascular disease
• Scaffold
• Tissue engineering
• Vascular graft

• Humans
• Blood Vessel Prosthesis
• Tissue Engineering/methods
• Bioprosthesis
• Biocompatible Materials
• Cardiovascular Diseases
• Tissue Scaffolds

• Angiogenesis
• Gel-in-oil
• Image analysis
• Nanogel
• Transdermal delivery
• bFGF

• Endothelial Cells
• Neovascularization, Physiologic
• Nanogels
• Cardiovascular Physiological Phenomena

• Biomedical application
• Extracellular matrix
• Tissue engineering scaffold

• Tissue Engineering/methods
• Biomimetics
• Tissue Scaffolds/chemistry
• Extracellular Matrix/chemistry
• Regenerative Medicine/methods

• endothelialization
• human-induced pluripotent stem cell
• tissue-engineered vascular graft
• vascular smooth muscle

• Humans
• Blood Vessel Prosthesis
• Induced Pluripotent Stem Cells
• Endothelial Cells
• Tissue Engineering

• artificial blood vessels
• braiding
• electrospinning
• graft
• knitting
• weaving

• No. ZR2021QC112 The Natural Science Foundation of Shandong Province of China

• Biomimetics
• Cardiovascular diseases
• Small-diameter vascular grafts
• Surface modification
• Tissue engineering

• BK20220613 Natural Science Foundation of Jiangsu Province
• JC12022080 Science and Technology Project of Nantong City
• NRF-2021M3H4A1A04092878 Nano-Materials Technology Program
• National Research Foundation of Korea (NRF) Ministry of Science and ICT, South Korea
• No. 135421615008 Talent Introduction Program of Nantong University

• chronic wounds
• headache
• immune fitness
• impaired wound healing
• migraine
• slow healing wounds
• wound infection

• This research received no external funding

• Adventitial side
• Detergent
• Intimal side
• Porcine aorta
• Pressure decellularization

• Swine
• Animals
• Aorta, Thoracic
• Detergents/analysis
• Detergents/pharmacology
• Aorta
• Microscopy, Electron, Scanning
• Heart
• Tissue Engineering/methods
• Extracellular Matrix/chemistry
• Tissue Scaffolds/chemistry

• Boronic acid-based hydrogel
• Intimal hyperplasia
• Perivascular adipose tissue
• Rapamycin
• Smooth muscle cell
• Tissue adhesion

Liver transplantation is the only curative therapy for end stage liver disease, but is limited by the organ shortage, and is associated with the adverse consequences of immunosuppression. Repopulation of decellularised whole organ scaffolds with appropriate cells of recipient origin offers a theoretically attractive solution, allowing reliable and timely organ sourcing without the need for immunosuppression. Decellularisation methodologies vary widely but seek to address the conflicting objectives of removing the cellular component of tissues whilst keeping the 3D structure of the extra-cellular matrix intact, as well as retaining the instructive cell fate determining biochemicals contained therein. Liver scaffold recellularisation has progressed from small rodent in vitro studies to large animal in vivo perfusion models, using a wide range of cell types including primary cells, cell lines, foetal stem cells, and induced pluripotent stem cells. Within these models, a limited but measurable degree of physiologically significant hepatocyte function has been reported with demonstrable ammonia metabolism in vivo. Biliary repopulation and function have been restricted by challenges relating to the culture and propagations of cholangiocytes, though advances in organoid culture may help address this. Hepatic vasculature repopulation has enabled sustainable blood perfusion in vivo, but with cell types that would limit clinical applications, and which have not been shown to have the specific functions of liver sinusoidal endothelial cells. Minority cell groups such as Kupffer cells and stellate cells have not been repopulated. Bioengineering by repopulation of decellularised scaffolds has significantly progressed, but there remain significant experimental challenges to be addressed before therapeutic applications may be envisaged.

• Regenerative
• Bioengineering
• Scaffolds
• Liver
• Decellularisation
• Recellularisation

• cell proliferation
• cell viability
• electrospinning
• human umbilical vein cells (HUVEC)
• human vascular fibroblast cells (HVF)
• poly (lactic-co-glycolic acid) (PLGA)
• polycaprolactone (PCL)
• tissue engineering

Patients with cardiovascular disease often need replacement or bypass of a diseased blood vessel. With disadvantages of both autologous blood vessels and synthetic grafts, tissue engineering is emerging as a promising alternative of advanced therapy medicinal products for individualized blood vessels. By reconditioning of a decellularized blood vessel with the recipient’s own peripheral blood, we have been able to prevent rejection without using immunosuppressants and prime grafts for efficient recellularization in vivo. Recently, decellularized veins reconditioned with autologous peripheral blood were shown to be safe and functional in a porcine in vivo study as a potential alternative for vein grafting. In this study, personalized tissue engineered arteries (P-TEA) were developed using the same methodology and evaluated for safety in a sheep in vivo model of carotid artery transplantation. Five personalized arteries were transplanted to carotid arteries and analyzed for safety and patency as well as with histology after four months in vivo. All grafts were fully patent without any occlusion or stenosis. The tissue was well cellularized with a continuous endothelial cell layer covering the luminal surface, revascularized adventitia with capillaries and no sign of rejection or infection. In summary, the results indicate that P-TEA is safe to use and has potential as clinical grafts.

•

Safety and functionality evaluation of a tissue engineered ATMP in a sheep model of carotid transplantation.

• ATMP
• Blood vessels
• Recellularization
• Regenerative medicine
• Scaffold
• Tissue engineering

• endothelialization
• immunoengineering
• macrophages
• monocytes
• vascular grafts

• Mice
• Animals
• Monocytes/metabolism
• Tissue Engineering
• Myocytes, Smooth Muscle
• Endothelial Cells
• Blood Vessel Prosthesis
• Endothelium, Vascular

• R01 HL151196 NHLBI NIH HHS

• biomaterial
• biomimetics
• orientation
• scaffold
• tissue engineering
• tissue regeneration
• topography

• 81901903 National Natural Science Foundation of China
• BK20190356, BK20190354 Natural Science Foundation of Jiangsu Province
• 31900962 National Natural Science Foundation of China

• anti-angiogenic drugs
• endothelial progenitor cells
• melanoma vascularization
• vasculogenesis

• APP1163986 National Health and Medical Research Council

• Animals
• Aortic Valve
• Bioprosthesis
• Endothelial Progenitor Cells
• Heart Valve Prosthesis
• Heart Valves
• Hepatocyte Growth Factor/pharmacology
• Swine
• Tissue Engineering/methods

• Animals
• Blood Vessel Prosthesis
• Endothelium, Vascular/physiology
• Polymers
• Porosity
• Rabbits
• Vascular Grafting

• National Natural Science Foundation of China

Stem cell-based therapeutics have gained tremendous attention in recent years due to their wide range of applications in various degenerative diseases, injuries, and other health-related conditions. Therapeutically effective bone marrow stem cells, cord blood- or adipose tissue-derived mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and more recently, induced pluripotent stem cells (iPSCs) have been widely reported in many preclinical and clinical studies with some promising results. However, these stem cell-only transplantation strategies are hindered by the harsh microenvironment, limited cell viability, and poor retention of transplanted cells at the sites of injury. In fact, a number of studies have reported that less than 5% of the transplanted cells are retained at the site of injury on the first day after transplantation, suggesting extremely low (<1%) viability of transplanted cells. In this context, 3D porous or fibrous national polymers (collagen, fibrin, hyaluronic acid, and chitosan)-based scaffold with appropriate mechanical features and biocompatibility can be used to overcome various limitations of stem cell-only transplantation by supporting their adhesion, survival, proliferation, and differentiation as well as providing elegant 3-dimensional (3D) tissue microenvironment. Therefore, stem cell-based tissue engineering using natural or synthetic biomimetics provides novel clinical and therapeutic opportunities for a number of degenerative diseases or tissue injury. Here, we summarized recent studies involving various types of stem cell-based tissue-engineering strategies for different degenerative diseases. We also reviewed recent studies for preclinical and clinical use of stem cell-based scaffolds and various optimization strategies.

• National Research Foundation of Korea
• Gachon University

• bioengineering
• cell- and tissue-based therapy
• humans
• regenerative medicine
• tissue engineering

• Animals
• Bioengineering
• Biomedical Engineering
• Blood Vessel Prosthesis
• Cardiovascular System
• Humans
• Tissue Engineering

• UL1 TR001863 NCATS NIH HHS

• MSCs
• exosomes
• immunomodulation
• inflammation
• liver disease
• regeneration

• Extracellular Vesicles/metabolism
• Fibrosis
• Humans
• Immunomodulation
• Liver Diseases/etiology
• Liver Diseases/metabolism
• Liver Diseases/therapy
• Mesenchymal Stem Cells/metabolism

We have designed a reinforced drug-loaded vascular graft composed of polycaprolactone (PCL) and polydioxanone (PDO) via a combination of electrospinning/3D printing approaches. To evaluate its potential for clinical application, we compared the in vivo blood compatibility and performance of PCL/PDO + 10%DY grafts doped with an antithrombotic drug (dipyridamole) with a commercial expanded polytetrafluoroethylene (e-PTFE) graft in a porcine model.

A total of 10 pigs (weight: 25–35 kg) were used in this study. We made a new 5-mm graft with PCL/PDO composite nanofiber via the electrospinning technique. We simultaneously implanted a commercially available e-PTFE graft (n = 5) and our PCL/PDO + 10%DY graft (n = 5) into the carotid arteries of the pigs. No anticoagulant/antiplatelet agent was administered during the follow-up period, and ultrasonography was performed weekly to confirm the patency of the two grafts in vivo. Four weeks later, we explanted and compared the performance of the two grafts by histological analysis and scanning electron microscopy (SEM).

No complications, such as sweating on the graft or significant bleeding from the needle hole site, were seen in the PCL/PDO + 10%DY graft immediately after implantation. Serial ultrasonographic examination and immunohistochemical analysis demonstrated that PCL/PDO + 10%DY grafts showed normal physiological blood flow and minimal lumen reduction, and pulsed synchronously with the native artery at 4 weeks after implantation. However, all e-PTFE grafts occluded within the study period. The luminal surface of the PCL/PDO + 10%DY graft in the transitional zone was fully covered with endothelial cells as observed by SEM.

The PCL/PDO + 10%DY graft was well tolerated, and no adverse tissue reaction was observed in porcine carotid models during the short-term follow-up. Colonization of the graft by host endothelial and smooth muscle cells coupled with substantial extracellular matrix production marked the regenerative capability. Thus, this material may be an ideal substitute for vascular reconstruction and bypass surgeries. Long-term observations will be necessary to determine the anti-thrombotic and remodeling potential of this device.

The online version contains supplementary material available at 10.1007/s13770-021-00422-4.

• 3D printing
• Electrospinning
• Endothelialization
• Nanofiber
• Vascular graft

• Cell–cell signaling
• Computational modeling
• Growth and remodeling
• Mechano-regulation
• Mechanobiology
• Tissue organization

• Biomechanical Phenomena
• Cell Communication
• Heart Valves/physiology
• Signal Transduction
• Tissue Engineering/methods

• 846617 H2020 Marie Skłodowska-Curie Actions
• 802967 European Research Council
• 771168 European Research Council

Coronary heart disease (CHD) is caused by narrowing or blockage of coronary arteries due to atherosclerosis. Coronary artery bypass grafting (CABG) is widely used for the treatment of severe CHD cases. Although autologous vessels are a preferred choice, healthy autologous vessels are not always available; hence there is a demand for tissue engineered vascular grafts (TEVGs) to be used as alternatives. However, producing clinical grade implantable TEVGs that could healthily survive in the host with long-term patency is still a great challenge. There are additional difficulties in producing small diameter (<6 mm) vascular conduits. As a result, there have not been TEVGs that are commercially available. Properties of vascular scaffolds such as tensile strength, thrombogenicity and immunogenicity are key factors that determine the biocompatibility of TEVGs. The source of vascular cells employed to produce TEVGs is a limiting factor for large-scale productions. Advanced technologies including the combined use of natural and biodegradable synthetic materials for scaffolds in conjunction with the use of mesenchyme stem cells or induced pluripotent stem cells (iPSCs) provide promising solutions for vascular tissue engineering. The aim of this review is to provide an update on various aspects in this field and the current status of TEVG clinical applications.

• induced pluripotent stem cells
• ischemic heart disease
• mesenchyme stem cells
• tissue engineered vascular grafts
• vascular tissue engineering

• failure
• immune response
• regeneration
• tissue-engineered vascular grafts

• Animals
• Biocompatible Materials/pharmacology
• Blood/immunology
• Blood Coagulation/drug effects
• Blood Vessel Prosthesis
• Humans
• Immunity
• Treatment Failure

• 277877758172, 819-2017 Ministerio de Ciencia, Tecnología e Innovación (Minciencias)

• cardiovascular diseases
• tissue engineering

• cardiovascular disease
• coating
• decellularize
• endothelial
• scaffold
• small diameter
• treatment

• biomimetics
• bioreactors
• in-vitro and in-vivo
• regenerative medicine
• scaffolds
• stem cells
• surface modification
• tissue engineering

• R01 HL138252 NHLBI NIH HHS
• UH3 TR002142 NCATS NIH HHS

• angiogenesis
• cell therapy
• decellularization
• vascular network formation
• vessels on a chip

• History, 20th Century
• History, 21st Century
• Humans
• Molecular Biology/history
• Periodicals as Topic

• antithrombotic therapy
• end-to-end anastomosis
• end-to-side anastomosis
• large-animal models
• patency
• small-diameter tissue engineered vascular grafts (SD-TEVGs)

• Animals
• Blood Vessel Prosthesis
• Blood Vessel Prosthesis Implantation
• Extracellular Matrix/metabolism
• Graft Rejection/etiology
• Humans
• Models, Animal
• Tissue Engineering

• Grant no. not applicable Odense University Hospital
• Grant no. not applicable Karen Elise Jensen
• Grant no. not applicable University of Southern Denmark
• #7051-00001A Innovation Fund Denmark
• #1530 S.C. Van Fonden

Endothelial progenitor cells (EPCs) have been broadly studied for several years due to their outstanding regenerative potential. Moreover, these cells might be a valuable source of genetic information for the preservation of endangered animal species. However, a controversy regarding their characterization still exists. The aim of this study was to isolate and compare the rabbit peripheral blood- and bone marrow-derived EPCs with human umbilical vein endothelial cells (HUVECs) in terms of their phenotype and morphology that could be affected by the passage number or cryopreservation as well as to assess their possible neuro-differentiation potential. Briefly, cells were isolated and cultured under standard endothelial conditions until passage 3. The morphological changes during the culture were monitored and each passage was analyzed for the typical phenotype using flow cytometry, quantitative real–time polymerase chain reaction (qPCR) and novel digital droplet PCR (ddPCR), and compared to HUVECs. The neurogenic differentiation was induced using a commercial kit. Rabbit cells were also cryopreserved for at least 3 months and then analyzed after thawing. According to the obtained results, both rabbit EPCs exhibit a spindle-shaped morphology and high proliferation rate. The both cell lines possess same stable phenotype: CD14⁻CD29⁺CD31⁻CD34⁻CD44⁺CD45⁻CD49f⁺CD73⁺CD90⁺CD105⁺CD133⁻CD146⁻CD166⁺VE-cadherin⁺VEGFR-2⁺SSEA-4⁺MSCA-1⁻vWF⁺eNOS⁺AcLDL⁺ALDH⁺vimentin⁺desmin⁺α-SMA⁺, slightly different from HUVECs. Moreover, both induced rabbit EPCs exhibit neuron-like morphological changes and expression of neuronal markers ENO2 and MAP2. In addition, cryopreserved rabbit cells maintained high viability (>85%) and endothelial phenotype after thawing. In conclusion, our findings suggest that cells expanded from the rabbit peripheral blood and bone marrow are of the endothelial origin with a stable marker expression and interesting proliferation and differentiation capacity.

• HUVECs
• bone marrow
• cryopreservation
• ddPCR
• endothelial progenitor cells
• flow cytometry
• neuro-transdifferentiation
• peripheral blood
• qPCR
• rabbit

• Animals
• Bone Marrow Cells/cytology
• Bone Marrow Cells/metabolism
• Cell Proliferation
• Cell Survival
• Cells, Cultured
• Coculture Techniques
• Cryopreservation
• Endothelial Progenitor Cells/cytology
• Endothelial Progenitor Cells/metabolism
• Genetic Markers
• Human Umbilical Vein Endothelial Cells/cytology
• Human Umbilical Vein Endothelial Cells/metabolism
• Humans
• Neurons/cytology
• Neurons/metabolism
• Peripheral Blood Stem Cells/cytology
• Peripheral Blood Stem Cells/metabolism
• Phenotype
• Rabbits

Endothelial progenitor cells (EPCs) are promising candidates for the cellular therapy of peripheral arterial and cardiovascular diseases. However, hitherto there is no specific marker(s) defining precisely EPCs. Herein, we are proposing a new in silico approach for finding novel EPC markers.

We assembled five groups of chosen EPC-related genes/factors using PubMed literature and Gene Ontology databases. This shortened database of EPC factors was fed into publically published transcriptome matrix to compare their expression between endothelial colony-forming cells (ECFCs), HUVECs, and two adult endothelial cell types (ECs) from the skin and adipose tissue. Further, the database was used for functional enrichment on Mouse Phenotype database and protein-protein interaction network analyses. Moreover, we built a digital matrix of healthy donors’ PBMCs (33 thousand single-cell transcriptomes) and analyzed the expression of these EPC factors.

Transcriptome analyses showed that BMP2, 4, and ephrinB2 were exclusively highly expressed in EPCs; the expression of neuropilin-1 and VEGF-C were significantly higher in EPCs and HUVECs compared with other ECs; Notch 1 was highly expressed in EPCs and skin-ECs; MIR21 was highly expressed in skin-ECs; PECAM-1 was significantly higher in EPCs and adipose ECs. Moreover, functional enrichment of EPC-related genes on Mouse Phenotype and STRING protein database has revealed significant relations between chosen EPC factors and endothelial and vascular functions, development, and morphogenesis, where ephrinB2, BMP2, and BMP4 were highly expressed in EPCs and were connected to abnormal vascular functions. Single-cell RNA-sequencing analyses have revealed that among the EPC-regulated markers in transcriptome analyses, (i) ICAM1 and Endoglin were weekly expressed in the monocyte compartment of the peripheral blood; (ii) CD163 and CD36 were highly expressed in the CD14+ monocyte compartment whereas CSF1R was highly expressed in the CD16+ monocyte compartment, (iii) L-selectin and IL6R were globally expressed in the lymphoid/myeloid compartments, and (iv) interestingly, PLAUR/UPAR and NOTCH2 were highly expressed in both CD14+ and CD16+ monocytic compartments.

The current study has identified novel EPC markers that could be used for better characterization of EPC subpopulation in adult peripheral blood and subsequent usage of EPCs for various cell therapy and regenerative medicine applications.

• Endothelial progenitor cells
• Multi-parametric flow cytometric analyses
• Protein-protein interaction network analyses
• Single-cell RNA-sequencing analyses
• Transcriptome analyses

Tissue-engineered vascular grafts (TEVGs) have enormous potential for vascular replacement therapy. However, thrombosis and intimal hyperplasia are important problems associated with TEVGs especially small diameter TEVGs (<6 mm) after transplantation. Endothelialization of TEVGs is a key point to prevent thrombosis. Here, we discuss different types of endothelialization and different seed cells of tissue-engineered vascular grafts. Meanwhile, endothelial heterogeneity is also discussed. Based on it, we provide a new perspective for selecting suitable types of endothelialization and suitable seed cells to improve the long-term patency rate of tissue-engineered vascular grafts with different diameters and lengths.

•

The material, diameter and length of tissue-engineered vascular graft are all key factors affecting its long-term patency.

• Tissue-engineered vascular grafts
• endothelial heterogeneity
• scaffold materials
• seed cells
• vascular endothelialization

• 3D and 4D printing
• bypass surgery
• cardiovascular disease
• decellularization
• human umbilical arteries
• small-diameter vascular grafts
• synthetic materials
• thermoresponsive materials
• tissue engineering
• vascular reconstruction

• Decellularization
• Fibrosis
• Inflammatory cells
• Vascular graft

• Tissue engineering
• arteries
• decellularization
• extracellular matrix
• sodium dodecyl sulfate
• vascular grafts

• Diabetes mellitus
• Islets of Langerhans
• Neo-Pancreas
• Re-endothelialization
• Tissue engineering

Liver disease is a major health problem that endangers human health worldwide. Currently, whole organ allograft transplantation is the gold standard for the treatment of end-stage liver disease. A shortage of suitable organs, high costs and surgical complications limit the application of liver transplantation. Mesenchymal stem cell therapy has been considered as a promising alternative approach for end-stage liver disease. Some clinical trials have confirmed the effectiveness of MSC therapy for liver disease, but its application has not been promoted and approved. There are still many issues that should be solved prior to using MSC therapy in clinical applications. The types of liver disease that are most suitable for MSC application should be determined, and the preparation and engraftment of MSCs should be standardized. These may be bottlenecks that limit the use of MSCs. We investigated 22 completed and several ongoing clinical trials to discuss these questions from a clinical perspective. We also discussed the important mechanisms by which MSCs play a therapeutic role in liver disease. Finally, we also proposed novel prospective approaches that can improve the therapeutic effect of MSCs.

• Cell therapy
• Liver disease
• Mesenchymal stem cells

• Endothelial Cells
• Humans
• Myocytes, Cardiac
• Pulsatile Flow
• Signal Transduction
• Stem Cells
• Stress, Mechanical

• T32 GM008349 NIGMS NIH HHS
• T32 GM135066 NIGMS NIH HHS

• PDMS
• extracellular matrix
• fluid shear stress
• integrin
• tissue-specific

• bone marrow stem cell
• decellularisation
• liver
• recellularisation
• scaffold
• sinusoids
• transplantation
• vasculature