From the Center for Tissue Engineering (C.A.V., L.J.B., M.P.V.); the Departments of Anesthesiology (C.A.V., L.J.B., M.P.V.), Cell Biology (L.J.B.), and Pathology (M.P.V.); and the Division of Plastic Surgery (J.S.) -all at the University of Massachusetts Medical School, Worcester. Address reprint requests to Dr. Charles A. Vacanti at

Here we report a unique cellular reprogramming phenomenon, called stimulus-triggered acquisition of pluripotency (STAP), which requires neither nuclear transfer nor the introduction of transcription factors. In STAP, strong external stimuli such as a transient low-pH stressor reprogrammed mammalian somatic cells, resulting in the generation of pluripotent cells. Through real-time imaging of STAP cells derived from purified lymphocytes, as well as gene rearrangement analysis, we found that committed somatic cells give rise to STAP cells by reprogramming rather than selection. STAP cells showed a substantial decrease in DNA methylation in the regulatory regions of pluripotency marker genes. Blastocyst injection showed that STAP cells efficiently contribute to chimaeric embryos and to offspring via germline transmission. We also demonstrate the derivation of robustly expandable pluripotent cell lines from STAP cells. Thus, our findings indicate that epigenetic fate determination of mammalian cells can be markedly converted in a context-dependent manner by strong environmental cues.

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Objective: Previous successful efforts to tissue engineer cartilage for an auricle have used an immunocompromised nude mouse xenograft model. Subsequent efforts in an immunocompetent autogenous animal model have been less successful because of an inflammatory response directed against the foreign scaffold polymer used to provide an auricular shape. We studied an alternative polymer material and surgical technique to engineer autogenous cartilage in the shape of a human ear helix using injectable hydrogel scaffolding, Pluronic F-127 (polyethylene oxide and polypropylene oxide). Subject: Yorkshire swine. Material and Methods: Fresh autogenous chondrocytes were suspended in a biodegradable, biocompatible co-polymer hydrogel, Pluronic F-127, at a concentration of 3 ؋ 10 7 cells/mL. To support the contour of the implant, a skin fold channel in the shape of the helix of a human ear was created in the skin in three sites on the ventral surface of the animal. The cellhydrogel suspension was injected through the skin fold channel. For controls, injections were made into identical channels using either cells alone or the Pluronic F-127 without cells. After 10 weeks, the specimens were excised and examined both grossly and histologically. Results: Grossly, all implants retained a helical-like shape.

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A tissue-engineered human sized auricle of normal anatomic definition can be generated in an immunocompetent large-animal model using a mold technique. Although further refinements will be necessary, the technique appears promising for potential use in patients with microtia.

An adult human-sized auricle and nasal tip cartilaginous structure can be grown entirely in vitro using principles of tissue engineering.