This study describes the use of a previously reported chimerised monoclonal antibody (mAb), ch2448, to kill human embryonic stem cells (hESCs) in vivo and prevent or delay the formation of teratomas. ch2448 was raised against hESCs and was previously shown to effectively kill ovarian and breast cancer cells in vitro and in vivo. The antigen target was subsequently found to be Annexin A2, an oncofetal antigen expressed on both embryonic cells and cancer cells. Against cancer cells, ch2448 binds and kills via antibody‐dependent cell‐mediated cytotoxicity (ADCC) and/or antibody‐drug conjugate (ADC) routes. Here, we investigate if the use of ch2448 can be extended to hESC. ch2448 was found to bind specifically to undifferentiated hESC but not differentiated progenitors. Similar to previous study using cancer cells, ch2448 kills hESC in vivo either indirectly by eliciting ADCC or directly as an ADC. The treatment with ch2448 post‐transplantation eliminated the in vivo circulating undifferentiated cells and prevented or delayed the formation of teratomas. This surveillance role of ch2448 adds an additional layer of safeguard to enhance the safety and efficacious use of pluripotent stem cell‐derived products in regenerative medicine. Thereby, translating the use of ch2448 in the treatment of cancers to a proof of concept study in hESC (or pluripotent stem cell [PSC]), we show that mAbs can also be used to eliminate teratoma forming cells in vivo during PSC‐derived cell therapies. We propose to use this strategy to complement existing methods to eliminate teratoma‐forming cells in vitro. Residual undifferentiated cells may escape in vitro removal methods and be introduced into patients together with the differentiated cells.
BACKGROUND: The normal imaging appearances of the common agents used in injection mammoplasty and the challenges of mammography screening will be reviewed. METHODS: The local database from a tertiary hospital was accessed for imaging cases of injection mammoplasty. RESULTS: Free silicone is seen as multiple high-density opacities on mammograms. Silicone deposits can often be seen within axillary nodes due to lymphatic migration. Sonographically, a snowstorm appearance is seen when the silicone is diffusely distributed. On MRI, free silicone is hypointense on T1-weighted and hyperintense on T2-weighted images, with no contrast enhancement. Mammograms have a limited role in screening due to the high density of silicone. MRI is often required in these patients. Polyacrylamide gel and hyaluronic acid are seen as multiple collections on mammography. Polyacrylamide gel collections are of the same density as cysts, while hyaluronic acid collections are of higher density but less dense than silicone. On ultrasound, both can appear anechoic or show variable internal echoes. MRI demonstrates fluid signal with hypointense T1-weighted and hyperintense T2-weighted signal. Mammographic screening is possible if the injected material is located predominantly in the retro-glandular space without obscuring the breast parenchyma. On mammograms, autologous fat locules appear as lucent masses. Rim calcification can be seen if fat necrosis had developed. On ultrasound, focal fat collections can demonstrate varying levels of internal echogenicity, depending on the stage of fat necrosis. Mammographic screening is usually possible for patients after autologous fat injection as fat is hypodense compared to breast parenchyma. However, the dystrophic calcification associated with fat necrosis may mimic abnormal breast calcification. In such cases, MRI can be utilized as a problem-solving tool. CONCLUSION: It is important for the radiologist to recognize the type of injected material on the various imaging modalities and recommend the best modality for screening.
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