title: Economic 3D-printing approach for transplantation of human stem cell-derived β-like cells.
abstract: Transplantation of human pluripotent stem cells (hPSC) differentiated into insulin-producing β cells is a regenerative medicine approach being investigated for diabetes cell replacement therapy. This report presents a multifaceted transplantation strategy that combines differentiation into stem cell-derived β (SC-β) cells with 3D printing. By modulating the parameters of a low-cost 3D printer, we created a macroporous device composed of polylactic acid (PLA) that houses SC-β cell clusters within a degradable fibrin gel. Using finite element modeling of cellular oxygen diffusion-consumption and an in vitro culture system that allows for culture of devices at physiological oxygen levels, we identified cluster sizes that avoid severe hypoxia within 3D-printed devices and developed a microwell-based technique for resizing clusters within this range. Upon transplantation into mice, SC-β cell-embedded 3D-printed devices function for 12 weeks, are retrievable, and maintain structural integrity. Here, we demonstrate a novel 3D-printing approach that advances the use of differentiated hPSC for regenerative medicine applications and serves as a platform for future transplantation strategies.
authors.affiliation: Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Department of Biomedical Engineering, Washington University School of Medicine, Campus Box 8127, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Song
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Millman
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D010100:Oxygen / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry; D066330:Printing, Three-Dimensional; D013234:Stem Cells / Q000166:cytology; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D020100:Hydrogels; D007328:Insulin; D011091:Polyesters; C033616:poly(lactide); D005947:Glucose; D010100:Oxygen