Historically believed to be a homogeneous cell type that is often overlooked, fibroblasts are more and more understood to be heterogeneous in nature. Though the mechanisms behind how fibroblasts participate in homeostasis and pathology are just beginning to be understood, these cells are believed to be highly dynamic and play key roles in fibrosis and remodeling. Focusing primarily on fibroblasts within the skin and during wound healing, we describe the field's current understanding of fibroblast heterogeneity in form and function. From differences due to embryonic origins to anatomical variations, we explore the diverse contributions that fibroblasts have in fibrosis and plasticity. Following this, we describe molecular techniques used in the field to provide deeper insights into subpopulations of fibroblasts and their varied roles in complex processes such as wound healing. Limitations to current work are also discussed, with a focus on future directions that investigators are recommended to take in order to gain a deeper understanding of fibroblast biology and to develop potential targets for translational applications in a clinical setting.
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http://dx.doi.org/10.3390/biomedicines11082264 | DOI Listing |
Alzheimers Dement
December 2024
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Background: Biorepositories play an integral role in the advancement of our understanding of neurodegenerative diseases and improving human health outcomes. Research efforts are accelerated when access to high-quality clinical specimens is made available from a large, diverse participant group. Indiana University is home to three important neurodegenerative disease-focused biorepositories including the NIA-funded National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD), the NINDS-funded Biospecimen Exchange for Neurological Disorders (BioSEND), and the Michael J.
View Article and Find Full Text PDFBackground: Alzheimer's disease is characterized by early decreases in cerebral glucose metabolism which are linked to reduced glucose transporter 1 (GLUT1) expression at the blood-brain barrier (BBB). Another key disease hallmark is the abundance of Aβ peptides as plaques in the brain which arise from the processing of the amyloid precursor protein (APP). Autosomal dominant inherited mutations causatively link APP itself to AD, rendering it imperative to fully understand APP's physiological functions to define the underlying biology of AD.
View Article and Find Full Text PDFCurr Protoc
January 2025
Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana.
Human induced pluripotent stem cell (hiPSC)-based disease modeling can be successfully recapitulated to mimic disease characteristics across various human pathologies. Glaucoma, a progressive optic neuropathy, primarily affects the retinal ganglion cells (RGCs). While multiple groups have successfully generated RGCs from non-diseased hiPSCs, producing RGCs from glaucomatous human samples holds significant promise for understanding disease pathology by revealing patient-specific disease signatures.
View Article and Find Full Text PDFCurr Mol Med
January 2025
Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou 256603, China.
Most chronic respiratory diseases often lead to the clinical manifestation of pulmonary fibrosis. Inflammation and immune disorders are widely recognized as primary contributors to the onset of pulmonary fibrosis. Given that macrophages are predominantly responsible for inflammation and immune disorders, in this review, we first focused on the role of different subpopulations of macrophages in the lung and discussed the crosstalk between macrophages and other immune cells, such as neutrophils, regulatory T cells, NKT cells, and B lymphocytes during pulmonary fibrogenesis.
View Article and Find Full Text PDFSci Rep
January 2025
Nordic Bioscience, Immunoscience, Herlev Hovedgade 205-207, Herlev, 2730, Denmark.
Understanding how inflammatory cytokines influence profibrogenic wound healing responses in fibroblasts is important for understanding the pathogenesis of fibrosis. TNF-α and IL-13 are key cytokines in Th1 and Th2 immune responses, respectively, while TGF-β1 is the principal pro-fibrotic mediator. We show that 12-day fibroblast culture with TNF-α or IL-13 induces fibrogenesis, marked by progressively increasing type III and VI collagen formation, and that TGF-β1 co-stimulation amplifies these effects.
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