• Artery
• Cellular reprogramming
• Collateral arteries
• Development
• Endothelial cells
• Genetic lineage tracing
• Regeneration

The global incidence of asthma, a leading respiratory disorder affecting more than 235 million people, has dramatically increased in recent years. Characterized by chronic airway inflammation and an imbalanced response to airborne irritants, this chronic condition is associated with elevated levels of inflammatory factors and symptoms such as dyspnea, cough, wheezing, and chest tightness. Conventional asthma therapies, such as corticosteroids, long-acting β-agonists, and anti-inflammatory agents, often evoke diverse adverse reactions and fail to reduce symptoms and hospitalization rates over the long term effectively. These limitations have prompted researchers to explore innovative therapeutic strategies, including stem cell-related interventions, offering hope to those afflicted with this incurable disease. In this review, we describe the characteristics of stem cells and critically assess the potential and challenges of stem cell-based therapies to improve disease management and treatment outcomes for asthma and other diseases.

• Asthma
• Stem cell
• Therapy
• Embryonic stem cells
• Induced pluripotent stem cells
• Mesenchymal stem cells
• Adult stem cells

• Embryonic stem cell
• Endothelial cells
• Endothelial colony forming cells
• Induced Pluripotent stem Cells
• Regeneration
• Stem cells

• Humans
• Human Embryonic Stem Cells/cytology
• Neovascularization, Physiologic
• Fetal Blood/cytology
• Animals
• Endothelial Cells/cytology
• Endothelial Cells/metabolism
• Cell Proliferation
• Cell Differentiation
• Mice
• Endothelial Progenitor Cells/cytology
• Adult
• Cells, Cultured
• Angiogenesis

• Université Paris-Saclay Université Paris-Saclay
• Inserm Inserm
• inserm inserm
• ANR-11-INBS-0009 Infrastructure INGESTEM ANR

• Biological sciences
• Developmental biology
• Molecular biology

• biomaterials
• cardiac tissue engineering
• cardiomyocyte
• heart-on-a-chip
• iPSC
• myocardium

• Humans
• Tissue Engineering/methods
• Myocytes, Cardiac
• Biocompatible Materials
• Lab-On-A-Chip Devices
• Induced Pluripotent Stem Cells
• Myocardium

• R01 HL076485 NHLBI NIH HHS
• 2R01 HL076485 NIH HHS

• Blood vessels
• Endothelial cells
• Induced pluripotent stem cell
• Pericytes
• Smooth muscle cells
• Tissue engineering vascular graft
• Vascular organoids

• buffalo
• early pregnancy detection
• implantation
• maternal recognition of pregnancy
• miRNA expression

• angiocrine
• endothelial cells
• fibrosis
• regeneration
• vascular

• Cardiovascular disease
• Cell differentiation and regenerative medicine
• Direct cell reprogramming
• Endothelial cells
• Neovascularization

• 2020M3A9I4038454 National Research Foundation of Korea
• 2020R1A2C3003784 National Research Foundation of Korea
• 19CDA34760061 AHA Career Development Award
• 20TPA35490282 AHA Transformational Project Award
• HV22C0138 Korea Health Industry Development Institute
• 20016564 Ministry of Trade, Industry and Energy
• 6-2021-0178 Yonsei University College of Medicine
• 27302C0138 NIEHS NIH HHS
• R01HL150877 NHLBI NIH HHS
• NHLBI

Fetal exposure to gestational diabetes mellitus (GDM) predisposes children to future health complications including type-2 diabetes mellitus, hypertension, and cardiovascular disease. A key mechanism by which these complications occur is through stress-induced dysfunction of endothelial progenitor cells (EPCs), including endothelial colony-forming cells (ECFCs). Although several approaches have been previously explored to restore endothelial function, their widespread adoption remains tampered by systemic side effects of adjuvant drugs and unintended immune response of gene therapies. Here, we report a strategy to rejuvenate circulating vascular progenitor cells by conjugation of drug-loaded liposomal nanoparticles directly to the surface of GDM-exposed ECFCs (GDM-ECFCs). Bioactive nanoparticles can be robustly conjugated to the surface of ECFCs without altering cell viability and key progenitor phenotypes. Moreover, controlled delivery of therapeutic drugs to GDM-ECFCs is able to normalize transgelin (TAGLN) expression and improve cell migration, which is a critical key step in establishing functional vascular networks. More importantly, sustained pseudo-autocrine stimulation with bioactive nanoparticles is able to improve in vitro and in vivo vasculogenesis of GDM-ECFCs. Collectively, these findings highlight a simple, yet promising strategy to rejuvenate GDM-ECFCs and improve their therapeutic potential. Promising results from this study warrant future investigations on the prospect of the proposed strategy to improve dysfunctional vascular progenitor cells in the context of other chronic diseases, which has broad implications for addressing various cardiovascular complications, as well as advancing tissue repair and regenerative medicine.

Drug-loaded liposomal nanoparticles conjugated to endothelial colony-forming cells can improve the vasculogenic potential of vascular progenitor cells exposed to gestational diabetes mellitus.

Mandibular defects caused by injuries, tumors, and infections are common and can severely affect mandibular function and the patient’s appearance. However, mandible reconstruction with a mandibular bionic structure remains challenging. Inspired by the process of intramembranous ossification in mandibular development, a hierarchical vascularized engineered bone consisting of angiogenesis and osteogenesis modules has been produced. Moreover, the hierarchical vascular network and bone structure generated by these hierarchical vascularized engineered bone modules match the particular anatomical structure of the mandible. The ultra-tough polyion complex has been used as the basic scaffold for hierarchical vascularized engineered bone for ensuring better reconstruction of mandible function. According to the results of in vivo experiments, the bone regenerated using hierarchical vascularized engineered bone is similar to the natural mandibular bone in terms of morphology and genomics. The sonic hedgehog signaling pathway is specifically activated in hierarchical vascularized engineered bone, indicating that the new bone in hierarchical vascularized engineered bone underwent a process of intramembranous ossification identical to that of mandible development. Thus, hierarchical vascularized engineered bone has a high potential for clinical application in mandibular defect reconstruction. Moreover, the concept based on developmental processes and bionic structures provides an effective strategy for tissue regeneration.

The timely management of skin wounds has been an unmet clinical need for centuries. While there have been several attempts to accelerate wound healing and reduce the cost of hospitalisation and the healthcare burden, there remains a lack of efficient and effective wound healing approaches. In this regard, stem cell‐based therapies have garnered an outstanding position for the treatment of both acute and chronic skin wounds. Stem cells of different origins (e.g., embryo‐derived stem cells) have been utilised for managing cutaneous lesions; specifically, mesenchymal stem cells (MSCs) isolated from foetal (umbilical cord) and adult (bone marrow) tissues paved the way to more satisfactory outcomes. Since angiogenesis plays a critical role in all four stages of normal wound healing, recent therapeutic approaches have focused on utilising stem cells for inducing neovascularisation. In fact, stem cells can promote angiogenesis via either differentiation into endothelial lineages or secreting pro‐angiogenic exosomes. Furthermore, particular conditions (e.g., hypoxic environments) can be applied in order to boost the pro‐angiogenic capability of stem cells before transplantation. For tissue engineering and regenerative medicine applications, stem cells can be combined with specific types of pro‐angiogenic biocompatible materials (e.g., bioactive glasses) to enhance the neovascularisation process and subsequently accelerate wound healing. As such, this review article summarises such efforts emphasising the bright future that is conceivable when using pro‐angiogenic stem cells for treating acute and chronic skin wounds.

• Angiogenesis
• Differentiation
• Exosome
• Mesenchymal stem cells (MSCs)
• Stem cells
• Wound healing

Human hematopoietic stem/progenitor cell (HSPC)-based gene therapy is a promising direction for curing HIV-1-infected individuals. The zinc finger protein (2LTRZFP) designed to target the 2-LTR-circle junction of HIV-1 cDNA was previously reported as an intracellular antiviral molecular scaffold that prevents HIV integration. Here, we elucidate the efficacy and safety of using 2LTRZFP in human CD34⁺ HSPCs. We transduced 2LTRZFP which has the mCherry tag (2LTRZFPmCherry) into human CD34⁺ HSPCs using a lentiviral vector. The 2LTRZFPmCherry-transduced HSPCs were subsequently differentiated into macrophages. The expression levels of pro-apoptotic proteins of the 2LTRZFPmCherry-transduced HSPCs showed no significant difference from those of the non-transduced control. Furthermore, the 2LTRZFPmCherry-transduced HSPCs were successfully differentiated into mature macrophages, which had normal phagocytic function. The cytokine secretion assay demonstrated that 2LTRZFPmCherry-transduced CD34⁺ derived macrophages promoted the polarization towards classically activated (M1) subtypes. More importantly, the 2LTRZFPmCherry transduced cells significantly exhibited resistance to HIV-1 integration in vitro. Our findings demonstrate that the 2LTRZFPmCherry-transduced macrophages were found to be functionally and phenotypically normal, with no adverse effects of the anti-HIV-1 scaffold. Our data suggest that the anti-HIV-1 integrase scaffold is a promising antiviral molecule that could be applied to human CD34⁺ HSPC-based gene therapy for AIDS patients.

• anti-HIV-1 scaffold
• gene therapy
• hematopoietic stem/progenitor cell
• zinc finger domain
• zinc finger protein

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

Human induced pluripotent stem cells (hiPSCs) hold great promise for cardiovascular regeneration following ischemic injury. Considerable effort has been made toward the development and optimization of methods to differentiate hiPSCs into vascular cells, such as endothelial and smooth muscle cells (ECs and SMCs). In particular, hiPSC-derived ECs have shown robust potential for promoting neovascularization in animal models of cardiovascular diseases, potentially achieving significant and sustained therapeutic benefits. However, the use of hiPSC-derived SMCs that possess high therapeutic relevance is a relatively new area of investigation, still in the earlier investigational stages. In this review, we first discuss different methodologies to derive vascular cells from hiPSCs with a particular emphasis on the role of key developmental signals. Furthermore, we propose a standardized framework for assessing and defining the EC and SMC identity that might be suitable for inducing tissue repair and regeneration. We then highlight the regenerative effects of hiPSC-derived vascular cells on animal models of myocardial infarction and hindlimb ischemia. Finally, we address several obstacles that need to be overcome to fully implement the use of hiPSC-derived vascular cells for clinical application.

• cardiovascular disease
• endothelial cell
• human induced pluripotent stem cell
• regenerative medicine
• smooth muscle cell
• stem cell

• 3D printing
• PGSA
• stem cells
• tissue engineering
• vascular construct

• atherosclerosis
• cardiology
• endothelial cell
• genomics
• peripheral arterial disease

• Animals
• Atherosclerosis/complications
• Atherosclerosis/therapy
• Endothelial Cells/physiology
• Genome-Wide Association Study
• Genomics/trends
• High-Throughput Nucleotide Sequencing
• Humans
• In Vitro Techniques
• Intermittent Claudication/therapy
• Ischemia/complications
• Leg Ulcer/etiology
• Leg Ulcer/therapy
• Mice
• Models, Animal
• Nanoparticles/therapeutic use
• Neovascularization, Physiologic
• Peripheral Arterial Disease/economics
• Peripheral Arterial Disease/genetics
• Peripheral Arterial Disease/therapy
• Pluripotent Stem Cells
• Single-Cell Analysis
• Translational Research, Biomedical
• Wound Healing

• R35 HL144475 NHLBI NIH HHS
• T32 HL098049 NHLBI NIH HHS

• angiogenic exosomes
• cardiac regeneration
• cell therapy
• myocardial infarction
• stem cell

• Angiogenesis Inducing Agents/therapeutic use
• Animals
• Disease Models, Animal
• Exosomes/metabolism
• Heart Diseases/metabolism
• Heart Diseases/therapy
• Rats
• Stem Cell Transplantation/methods
• Zebrafish

• regenerative medicine
• stem cells
• tissue engineering
• urethra
• urethroplasty
• urothelial cells

• Rapidly forming hydrogel
• bioorthogonal chemistry
• cell encapsulation
• double network
• vascularization

• Endothelial
• Tissue engineering
• Vascularization
• Vessel formation

• Blastocyst cells
• Embryoid body
• Endothelial differentiation
• fli:GFP
• kdrl:GFP

Cardiovascular disease, ranging from congenital heart disease to adult myocardial infarction, is the leading cause of death worldwide. In pursuit of reliable cardiovascular regenerative medicine, human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), offer plenty of potential cell-based applications. HPSCs are capable of proliferating indefinitely in an undifferentiated state, and are also pluripotent, being able to differentiate into virtually any somatic cell types given specific stepwise cues, thus representing an unlimited source to generate functional cardiovascular cells for heart regeneration. Here we recapitulated current advances in developing efficient protocols to generate hPSC-derived cardiovascular cell lineages, including cardiomyocytes, endothelial cells, and epicardial cells. We also discussed applications of hPSC-derived cells in combination with compatible bioactive materials, promising trials of cell transplantation in animal models of myocardial infarction, and potential hurdles to bring us closer to the ultimate goal of cell-based heart repair.

•

HPSCs hold tremendous therapeutic potential for treating CVDs.

• Cardiovascular cells
• Human pluripotent stem cells
• Tissue engineering

• endothelial cell
• endothelium
• fibroblast
• human
• regeneration

• Angiogenesis
• Coronary artery
• Endothelial cell
• Functional maturation
• Pluripotent stem cell
• Substrate topography

• angiogenesis
• from bench to bedside
• induced pluripotent stem cells
• tissue engineering
• tissue regeneration

• 3D EB formation
• Endothelial cells
• Human stem cells
• Tissue engineering

• Cell Differentiation/genetics
• Cell Differentiation/physiology
• Embryonic Stem Cells/cytology
• Embryonic Stem Cells/metabolism
• Endothelial Cells/cytology
• Endothelial Cells/metabolism
• Humans
• Neovascularization, Physiologic/genetics
• Neovascularization, Physiologic/physiology
• Tissue Engineering

• Scientific Research Foundation of the Education Department of Anhui Province, China.

Endothelial cells (ECs) are required for a multitude of cardiovascular clinical applications, such as revascularization of ischemic tissues or endothelialization of tissue engineered grafts. Patient derived primary ECs are limited in number, have donor variabilities and their in vitro phenotypes and functions can deteriorate over time. This necessitates the exploration of alternative EC sources. Although there has been a recent surge in the use of pluripotent stem cell derived endothelial cells (PSC-ECs) for various cardiovascular clinical applications, current differentiation protocols yield a heterogeneous EC population, where their specification into arterial or venous subtypes is undefined. Since arterial and venous ECs are phenotypically and functionally different, inappropriate matching of exogenous ECs to host sites can potentially affect clinical efficacy, as exemplified by venous graft mismatch when placed into an arterial environment. Therefore, there is a need to design and employ environmental cues that can effectively modulate PSC-ECs into a more homogeneous arterial or venous phenotype for better adaptation to the host environment, which will in turn contribute to better application efficacy. In this review, we will first give an overview of the developmental and functional differences between arterial and venous ECs. This provides the foundation for our subsequent discussion on the different bioengineering strategies that have been investigated to varying extent in providing biochemical and biophysical environmental cues to mature PSC-ECs into arterial or venous subtypes. The ability to efficiently leverage on a combination of biochemical and biophysical environmental cues to modulate intrinsic arterio-venous specification programs in ECs will greatly facilitate future translational applications of PSC-ECs. Since the development and maintenance of arterial and venous ECs in vivo occur in disparate physio-chemical microenvironments, it is conceivable that the application of these environmental factors in customized combinations or magnitudes can be used to selectively mature PSC-ECs into an arterial or venous subtype.

• arterial specification
• endothelial cells
• environmental cues
• functional maturation
• human pluripotent stem cells
• shear stress
• substrate topography

• cardiovascular disease
• cell transplantation
• endothelial cells
• regeneration
• stem cell
• tissue engineering

• Angiogenesis
• Endothelial progenitor cells
• Hydrogel
• Mesenchymal cells
• Stem cells
• Vascularization
• Vasculogenesis
• iPS cells

• Endothelial Cells/cytology
• Humans
• Microvessels/cytology
• Pericytes/cytology
• Pluripotent Stem Cells/cytology
• Tissue Engineering/trends

• R01 AR069038 NIAMS NIH HHS
• R01 HL128452 NHLBI NIH HHS
• R01HL128452 National Heart, Lung, and Blood Institute
• R21AI123883 National Institute of Allergy and Infectious Diseases
• R21 AI123883 NIAID NIH HHS
• R01AR069038 National Institute of Arthritis and Musculoskeletal and Skin Diseases

• Adult human liver cells
• Bioink
• Biomaterials
• Bioprinting
• Diabetes
• Human embryonic stem
• Islet cells
• Mesenchymal stem cells
• Pluripotent stem cells
• Stem cell
• Tissue engineering
• β-cells

• SC2 HL134642 NHLBI NIH HHS

• ETV2
• Endothelial
• GATA2
• Half-life
• Hematopoiesis
• Modified RNA
• Primate
• Stem cells
• UTR
• Untranslated region

• COL1A1
• endothelial cells
• extracellular matrix

Engineered tissues are a promising tool for addressing the growing need for tissues and organs in surgical reconstructions. Prevascularization of implanted tissues is expected to enhance survival prospects post transplantation and minimize deficiencies and/or hypoxia deeper in the tissue. Here, we fabricate a three-dimensional, prevascularized engineered muscle containing human myoblasts, genetically modified endothelial cells secreting angiopoietin 1 (ANGPT1) and genetically modified smooth muscle cells secreting vascular endothelial growth factor (VEGF). The genetically engineered human muscle shows enhanced host neovascularization and myogenesis following transplantation into a mouse host, compared to the non-secreting control. The vascular, genetically modified cells have been cleared for clinical trials and can be used to construct autologous vascularized tissues. Therefore, the described genetically engineered vascularized muscle has the potential to be fully translated to the clinical setting to overcome autologous tissue shortage and to accelerate host neovascularization and integration of engineered grafts following transplantation.

Luba Perry et al. report transplantation of engineered prevascularized human muscle into mice to repair an abdominal muscle defect. They show that genetically engineering smooth muscle cells to secrete VEGF and endothelial cells to secrete ANGPT1 significantly improves host neovascularization and myogenesis.

The microvasculature plays a critical role in human physiology and is closely associated to various human diseases. By combining advanced microfluidic-based techniques, the engineered 3D microvascular network model provides a precise and reproducible platform to study the microvasculature in vitro, which is an essential and primary component to engineer organ-on-chips and achieve greater biological relevance. In this review, we discuss current strategies to engineer microvessels in vitro, which can be broadly classified into endothelial cell lining-based methods, vasculogenesis and angiogenesis-based methods, and hybrid methods. By closely simulating relevant factors found in vivo such as biomechanical, biochemical, and biological microenvironment, it is possible to create more accurate organ-specific models, including both healthy and pathological vascularized microtissue with their respective vascular barrier properties. We further discuss the integration of tumor cells/spheroids into the engineered microvascular to model the vascularized microtumor tissue, and their potential application in the study of cancer metastasis and anti-cancer drug screening. Finally, we conclude with our commentaries on current progress and future perspective of on-chip vascularization techniques for fundamental and clinical/translational research.

• microfluidics
• organ-on-a-chip
• tissue engineering
• vascularization
• vascularized tumor model

• HSCs
• MACS
• PCR
• flow cytometry
• rabbit CD34

• Cardiovascular disease
• Endothelial cell
• Human pluripotent stem cell
• Regenerative medicine
• Stem cell therapy

• Cardiovascular Diseases/therapy
• Cell Differentiation
• Endothelial Progenitor Cells/cytology
• Endothelial Progenitor Cells/transplantation
• Humans
• Models, Biological
• Pluripotent Stem Cells/cytology
• Regeneration
• Regenerative Medicine/methods
• Regenerative Medicine/trends

• DP3 DK094346 NIDDK NIH HHS
• DP3 DK108245 NIDDK NIH HHS
• R01 HL127759 NHLBI NIH HHS
• R01 HL129511 NHLBI NIH HHS

• Animal models
• Clinical studies
• In vitro
• Scaffolds
• TEBV
• Tissue engineered blood vessels
• Tissue engineering

New approaches in regenerative medicine and vasculogenesis have generated a demand for sufficient numbers of human endothelial cells (ECs). ECs and their progenitors reside on the interior surface of blood and lymphatic vessels or circulate in peripheral blood; however, their numbers are limited, and they are difficult to expand after isolation. Recent advances in human induced pluripotent stem cell (hiPSC) research have opened possible avenues to generate unlimited numbers of ECs from easily accessible cell sources, such as the peripheral blood. In this study, we reprogrammed peripheral blood mononuclear cells, human umbilical vein endothelial cells (HUVECs), and human saphenous vein endothelial cells (HSVECs) into hiPSCs and differentiated them into ECs. The phenotype profiles, functionality, and genome stability of all hiPSC-derived ECs were assessed and compared with HUVECs and HSVECs. hiPSC-derived ECs resembled their natural EC counterparts, as shown by the expression of the endothelial surface markers CD31 and CD144 and the results of the functional analysis. Higher expression of endothelial progenitor markers CD34 and kinase insert domain receptor (KDR) was measured in hiPSC-derived ECs. An analysis of phosphorylated histone H2AX (γH2AX) foci revealed that an increased number of DNA double-strand breaks upon reprogramming into pluripotent cells. However, differentiation into ECs restored a normal number of γH2AX foci. Our hiPSCs retained a normal karyotype, with the exception of the HSVEC-derived hiPSC line, which displayed mosaicism due to a gain of chromosome 1. Peripheral blood from adult donors is a suitable source for the unlimited production of patient-specific ECs through the hiPSC interstage. hiPSC-derived ECs are fully functional and comparable to natural ECs. The protocol is eligible for clinical applications in regenerative medicine, if the genomic stability of the pluripotent cell stage is closely monitored.

• endothelial differentiation
• induced pluripotent stem cells
• peripheral blood mononuclear cells

• Biomarkers/metabolism
• Cell Differentiation/physiology
• Cells, Cultured
• Endothelial Cells/cytology
• Endothelial Cells/metabolism
• Fibroblasts/cytology
• Fibroblasts/metabolism
• Human Umbilical Vein Endothelial Cells/cytology
• Human Umbilical Vein Endothelial Cells/metabolism
• Humans
• Induced Pluripotent Stem Cells/cytology
• Induced Pluripotent Stem Cells/metabolism
• Leukocytes, Mononuclear/cytology
• Leukocytes, Mononuclear/metabolism
• Neovascularization, Physiologic/physiology
• Regenerative Medicine/methods

• EPCs
• cardiac
• heart
• ischemia
• progenitors
• reperfusion

• 3D culture
• Collagen
• Hepatocyte
• Liver extract
• Matrigel

Over the past years, vascular diseases have continued to threaten human health and increase financial burdens worldwide. Transplantation of allogeneic and autologous blood vessels is the most convenient treatment. However, it could not be applied generally due to the scarcity of donors and the patient’s condition. Developments in tissue engineering are contributing greatly with regard to this urgent need for blood vessels. Tissue engineering-derived blood vessels are promising alternatives for patients with aortic dissection/aneurysm. The aim of this review is to show the importance of advances in biomaterials development for the treatment of vascular disease. We also provide a comprehensive overview of the current status of tissue reconstruction from stem cells and transplantable cellular scaffold constructs, focusing on the combination of stem cells and tissue engineering for blood vessel regeneration and vascular disease treatment.

• Regeneration
• Scaffold material
• Stem cells
• Vascular tissue engineering

Brain microvascular endothelial cells (BMECs) separate the peripheral blood from the brain. These cells, which are surrounded by basal lamina, pericytes and glial cells, are highly interconnected through tight and gap junctions. Their permeability properties restrict the transfer of potentially useful therapeutic agents. In such a hermetic system, the gap junctional exchange of small molecules between cerebral endothelial and non-endothelial cells is crucial for maintaining tissue homeostasis. MicroRNA were shown to cross gap junction channels, thereby modulating gene expression and function of the recipient cell. It was also shown that, when altered, BMEC could be regenerated by endothelial cells derived from pluripotent stem cells. Here, we discuss the transfer of microRNA through gap junctions between BMEC, the regeneration of BMEC from induced pluripotent stem cells that could be engineered to express specific microRNA, and how such an innovative approach could benefit to the treatment of glioblastoma and other neurological diseases.

• blood capillary
• connexin43
• gap junction
• glioblastoma
• microRNA
• neurological disorders
• targeted therapy

• arterial endothelial cells
• arterial-specific functions
• human pluripotent stem cell differentiation
• myocardial infarction
• single-cell RNA-seq

• Animals
• Arteries/cytology
• CRISPR-Cas Systems
• Cell Line
• Endothelial Cells/cytology
• Endothelial Cells/transplantation
• Humans
• Mice
• Myocardial Infarction/therapy
• Neovascularization, Physiologic
• Pluripotent Stem Cells/physiology
• Sequence Analysis, RNA
• Tissue Engineering/methods

• UH2 TR000506 NCATS NIH HHS
• R01 AI066219 NIAID NIH HHS
• UH3 TR000506 NCATS NIH HHS
• T32 AI125231 NIAID NIH HHS
• U01 HL134655 NHLBI NIH HHS
• R01 HL093282 NHLBI NIH HHS
• R21 EB016381 NIBIB NIH HHS