Mesenchymal stromal cells (MSCs) continue to be proposed for clinical investigation to treat myriad diseases given their purported potential to stimulate endogenous regenerative processes, such as angiogenesis. However, MSC functional heterogeneity has hindered clinical success and still poses a substantial manufacturing challenge from a product quality control perspective. Here, a quantitative bioassay based on an enhanced-throughput is described, microphysiological system (MPS) to measure the specific bioactivity of MSCs to stimulate angiogenesis as a potential measure of MSC potency. Using this novel bioassay, MSCs derived from multiple donors at different passages are co-cultured with human umbilical vein endothelial cells and exhibit significant heterogeneity in angiogenic potency between donors and cell passage. Depending on donor source and cellular passage number, MSCs varied in their ability to stimulate tip cell dominant or stalk cell dominant phenotypes in angiogenic sprout morphology which correlated with expression levels of hepatocyte growth factor (HGF). These findings suggest that MSC angiogenic bioactivity may be considered as a possible potency attribute in MSC quality control strategies. Development of a reliable and functionally relevant potency assay for measuring clinically relevant potency attributes of MSCs will help to improve consistency in quality and thereby, accelerate clinical development of these cell-based products.
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http://dx.doi.org/10.1002/adbi.202300094 | DOI Listing |
Nano Converg
January 2025
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21205, USA.
bioRxiv
January 2025
Department of Chemistry, 409 McCormick Road, University of Virginia, Charlottesville, VA 22904.
Antibody production is central to protection against new pathogens and cancers, as well as to certain forms of autoimmunity. Antibodies often originate in the lymph node (LN), specifically at the extrafollicular border of B cell follicles, where T and B lymphocytes physically interact to drive B cell maturation into antibody-secreting plasmablasts. In vitro models of this process are sorely needed to predict aspects of the human immune response.
View Article and Find Full Text PDFLung fibrosis, characterized by chronic and progressive scarring, has no cure. Hallmarks are the accumulation of myofibroblasts and extracellular matrix, as well as vascular remodeling. The crosstalk between myofibroblasts and vasculature is poorly understood, with conflicting reports on whether angiogenesis and vessel density are increased or decreased in lung fibrosis.
View Article and Find Full Text PDFWe report on the design and fabrication of a novel circular pillar array as an interfacial barrier for microfluidic microphysiological systems ( ). Traditional barrier interfaces, such as porous membranes and microchannel arrays, present limitations due to inconsistent pore size, complex fabrication and device assembly, and lack of tunability using a scalable design. Our pillar array overcomes these limitations by providing precise control over pore size, porosity, and hydraulic resistance through simple modifications of pillar dimensions.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA.
The aberrant vascular response associated with tendon injury results in circulating immune cell infiltration and a chronic inflammatory feedback loop leading to poor healing outcomes. Studying this dysregulated tendon repair response in human pathophysiology has been historically challenging due to the reliance on animal models. To address this, our group developed the human tendon-on-a-chip (hToC) to model cellular interactions in the injured tendon microenvironment; however, this model lacked the key element of physiological flow in the vascular compartment.
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