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Advanced Science (Weinheim,... Jul 2021The thymus plays a key role in adaptive immunity by generating a diverse population of T cells that defend the body against pathogens. Various factors from disease and... (Review)
Review
The thymus plays a key role in adaptive immunity by generating a diverse population of T cells that defend the body against pathogens. Various factors from disease and toxic insults contribute to the degeneration of the thymus resulting in a fewer output of T cells. Consequently, the body is prone to a wide host of diseases and infections. In this review, first, the relevance of the thymus is discussed, followed by thymic embryological organogenesis and anatomy as well as the development and functionality of T cells. Attempts to regenerate the thymus include in vitro methods, such as forming thymic organoids aided by biofabrication techniques that are transplantable. Ex vivo methods that have shown promise in enhancing thymic regeneration are also discussed. Current regenerative technologies have not yet matched the complexity and functionality of the thymus. Therefore, emerging techniques that have shown promise and the challenges that lie ahead are explored.
Topics: Humans; Organogenesis; Regeneration; Rejuvenation; T-Lymphocytes; Thymus Gland
PubMed: 34306981
DOI: 10.1002/advs.202100543 -
Cellular and Molecular Life Sciences :... Jul 2020Epithelial to mesenchymal transition (EMT) is a complex plastic and reversible cellular process that has critical roles in diverse physiological and pathological... (Review)
Review
Epithelial to mesenchymal transition (EMT) is a complex plastic and reversible cellular process that has critical roles in diverse physiological and pathological phenomena. EMT is involved in embryonic development, organogenesis and tissue repair, as well as in fibrosis, cancer metastasis and drug resistance. In recent years, the ability to edit the genome using the clustered regularly interspaced palindromic repeats (CRISPR) and associated protein (Cas) system has greatly contributed to identify or validate critical genes in pathway signaling. This review delineates the complex EMT networks and discusses recent studies that have used CRISPR/Cas technology to further advance our understanding of the EMT process.
Topics: CRISPR-Cas Systems; Embryonic Development; Epithelial-Mesenchymal Transition; Gene Editing; Humans; Organogenesis; Signal Transduction
PubMed: 32008085
DOI: 10.1007/s00018-020-03449-3 -
Pediatric Nephrology (Berlin, Germany) Jul 2016Appreciation for the role of epigenetic modifications in the diagnosis and treatment of diseases is fast gaining attention. Treatment of chronic kidney disease stemming... (Review)
Review
Appreciation for the role of epigenetic modifications in the diagnosis and treatment of diseases is fast gaining attention. Treatment of chronic kidney disease stemming from diabetes or hypertension as well as Wilms tumor will all profit from knowledge of the changes in the epigenomic landscapes. To do so, it is essential to characterize the epigenomic modifiers and their modifications under normal physiological conditions. The transcription factor Pax2 was identified as a major epigenetic player in the early specification of the kidney. Notably, the progenitors of all nephrons that reside in the cap mesenchyme display a unique bivalent histone signature (expressing repressive epigenetic marks alongside activation marks) on lineage-specific genes. These cells are deemed poised for differentiation and commitment to the nephrogenic lineage. In response to the appropriate inducing signal, these genes lose their repressive histone marks, which allow for their expression in nascent nephron precursors. Such knowledge of the epigenetic landscape and the resultant cell fate or behavior in the developing kidney will greatly improve the overall success in designing regenerative strategies and tissue reprogramming methodologies from pluripotent cells.
Topics: Animals; Epigenesis, Genetic; Humans; Kidney; Organogenesis
PubMed: 26493068
DOI: 10.1007/s00467-015-3228-x -
Journal of the American Society of... Sep 2021
Topics: Organogenesis; Receptors, Immunologic
PubMed: 34465603
DOI: 10.1681/ASN.2021070900 -
Biomolecules Jun 2021The vasculature of stem-cell-derived liver organoids can be engineered using methods that recapitulate embryonic liver development. Hepatic organoids with a vascular... (Review)
Review
The vasculature of stem-cell-derived liver organoids can be engineered using methods that recapitulate embryonic liver development. Hepatic organoids with a vascular network offer great application prospects for drug screening, disease modeling, and therapeutics. However, the application of stem cell-derived organoids is hindered by insufficient vascularization and maturation. Here, we review different theories about the origin of hepatic cells and the morphogenesis of hepatic vessels to provide potential approaches for organoid generation. We also review the main protocols for generating vascularized liver organoids from stem cells and consider their potential and limitations in the generation of vascularized liver organoids.
Topics: Cell Culture Techniques; Cell Differentiation; Drug Evaluation, Preclinical; Genetic Engineering; Hepatocytes; Humans; Liver; Organogenesis; Organoids; Stem Cells
PubMed: 34208902
DOI: 10.3390/biom11070966 -
Current Osteoporosis Reports Feb 2015Synovial joint morphogenesis occurs through the condensation of mesenchymal cells into a non-cartilaginous region known as the interzone and the specification of... (Review)
Review
Synovial joint morphogenesis occurs through the condensation of mesenchymal cells into a non-cartilaginous region known as the interzone and the specification of progenitor cells that commit to the articular fate. Although several signaling molecules are expressed by the interzone, the mechanism is poorly understood. For treatments of cartilage injuries, it is critical to discover the presence of joint progenitor cells in adult tissues and their expression gene pattern. Potential stem cell niches have been found in different joint regions, such as the surface zone of articular cartilage, synovium, and groove of Ranvier. Inherited joint malformations as well as joint-degenerating conditions are often associated with other skeletal defects and may be seen as the failure of morphogenic factors to establish the correct microenvironment in cartilage and bone. Therefore, exploring how joints form can help us understand how cartilage and bone are damaged and develop drugs to reactivate this developing mechanism.
Topics: Homeostasis; Humans; Joints; Morphogenesis; Organogenesis
PubMed: 25431159
DOI: 10.1007/s11914-014-0247-7 -
Development (Cambridge, England) May 2014During organogenesis, various molecular and physical signals are orchestrated in space and time to sculpt multiple cell types into functional tissues and organs. The... (Review)
Review
During organogenesis, various molecular and physical signals are orchestrated in space and time to sculpt multiple cell types into functional tissues and organs. The complex and dynamic nature of the process has hindered studies aimed at delineating morphogenetic mechanisms in vivo, particularly in mammals. Recent demonstrations of stem cell-driven tissue assembly in culture offer a powerful new tool for modeling and dissecting organogenesis. However, despite the highly organotypic nature of stem cell-derived tissues, substantial differences set them apart from their in vivo counterparts, probably owing to the altered microenvironment in which they reside and the lack of mesenchymal influences. Advances in the biomaterials and microtechnology fields have, for example, afforded a high degree of spatiotemporal control over the cellular microenvironment, making it possible to interrogate the effects of individual microenvironmental components in a modular fashion and rapidly identify organ-specific synthetic culture models. Hence, bioengineering approaches promise to bridge the gap between stem cell-driven tissue formation in culture and morphogenesis in vivo, offering mechanistic insight into organogenesis and unveiling powerful new models for drug discovery, as well as strategies for tissue regeneration in the clinic. We draw on several examples of stem cell-derived organoids to illustrate how bioengineering can contribute to tissue formation ex vivo. We also discuss the challenges that lie ahead and potential ways to overcome them.
Topics: Animals; Biocompatible Materials; Bioengineering; Humans; Organogenesis; Organoids; Stem Cells; Tissue Engineering
PubMed: 24757002
DOI: 10.1242/dev.101048 -
Annual Review of Physiology Feb 2017Coronary artery disease (CAD) is the number one cause of death worldwide and involves the accumulation of plaques within the artery wall that can occlude blood flow to... (Review)
Review
Coronary artery disease (CAD) is the number one cause of death worldwide and involves the accumulation of plaques within the artery wall that can occlude blood flow to the heart and cause myocardial infarction. The high mortality associated with CAD makes the development of medical interventions that repair and replace diseased arteries a high priority for the cardiovascular research community. Advancements in arterial regenerative medicine could benefit from a detailed understanding of coronary artery development during embryogenesis and of how these pathways might be reignited during disease. Recent research has advanced our knowledge on how the coronary vasculature is built and revealed unexpected features of progenitor cell deployment that may have implications for organogenesis in general. Here, we highlight these recent findings and discuss how they set the stage to interrogate developmental pathways during injury and disease.
Topics: Animals; Cell Differentiation; Coronary Artery Disease; Coronary Vessels; Heart; Humans; Organogenesis; Stem Cells
PubMed: 27959616
DOI: 10.1146/annurev-physiol-022516-033953 -
Developmental Dynamics : An Official... Mar 2016Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly... (Review)
Review
Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans.
Topics: Animals; Embryo, Mammalian; Epithelium; Humans; Mesoderm; Organogenesis; Signal Transduction; Viscera
PubMed: 26638186
DOI: 10.1002/dvdy.24373 -
Developmental Dynamics : An Official... May 2020Despite significant advancements in understanding physiological properties of the carotid body, little attention has been paid to its organogenesis. This review... (Review)
Review
Despite significant advancements in understanding physiological properties of the carotid body, little attention has been paid to its organogenesis. This review addresses the molecular and cellular mechanisms underlying organogenesis of the carotid body in mammals. The carotid body consists of two types of cells, that is, glomus cells and sustentacular cells, that are derived from different origins. Glomus cells are derivatives of neural crest cells which form sympathetic ganglia. Sustentacular cells are derivatives of mesenchymal neural crest cells which colonize the third pharyngeal arch and form the wall of the third arch artery. Gene-targeting studies indicate that three elements are required for carotid body organogenesis: the carotid sinus nerve (CSN), third arch artery, and superior cervical sympathetic ganglion (SCG). The CSN sends sensory fibers and Schwann cells to the wall of the third arch artery. The third arch artery provides mesenchymal cells, which give rise to sustentacular cells. The nerve process from the SCG sends glomus cell progenitors into the carotid body primordium. The presence of stem cells in the adult carotid body was recently highlighted. The origin of stem cells, however, remains controversial. Based on embryonic development of the carotid body, this review proposes the origin of stem cells.
Topics: Animals; Carotid Body; Carotid Sinus; Neural Crest; Organogenesis
PubMed: 31837176
DOI: 10.1002/dvdy.144