Murata Kozue, Takamura Kanae, Watanabe Risa, Nagashima Akitomo, Miyauchi Miho, Miyauchi Yoshiteru, Masumoto Hidetoshi
Clinical Translational Research Program, Center for Biosystems Dynamics Research, RIKEN, 2-2-3 Minatojimaminami-Cho, Chuo-Ku, Kobe, 650-0047, Japan.
Department of Cardiovascular Surgery, Kyoto University Hospital, Kyoto, Japan.
Stem Cell Res Ther. 2025 Jun 25;16(1):303. doi: 10.1186/s13287-025-04424-0.
Bioactive cytokines such as vascular endothelial growth factor (VEGF) and Activin A are critical for the differentiation of stem cells into vascular endothelial cells and cardiomyocytes. However, production of the cytokines using conventional Escherichia coli or mammalian cell expression systems carries risks of immunogenicity and viral contamination. In this study, we developed a VEGF and Activin A plant expression system and demonstrated that plant-expressed VEGF and Activin A are as active as their commercial counterparts. We also showed that plant-expressed VEGF and Activin A are as efficient as human recombinant counterparts in inducing endothelial cells and cardiomyocytes from human pluripotent stem cells. These results suggest that plant-expressed VEGF and Activin A are promising alternatives for the safe and efficient production of cardiac cells, specifically cardiomyocytes and endothelial cells, for stem cell-based regenerative medicine.
生物活性细胞因子，如血管内皮生长因子（VEGF）和激活素A，对于干细胞分化为血管内皮细胞和心肌细胞至关重要。然而，使用传统的大肠杆菌或哺乳动物细胞表达系统生产这些细胞因子存在免疫原性和病毒污染的风险。在本研究中，我们开发了一种VEGF和激活素A植物表达系统，并证明植物表达的VEGF和激活素A与它们的商业同类产品一样具有活性。我们还表明，植物表达的VEGF和激活素A在诱导人多能干细胞分化为内皮细胞和心肌细胞方面与重组人源同类产品一样有效。这些结果表明，植物表达的VEGF和激活素A有望成为基于干细胞的再生医学中安全、高效生产心脏细胞（特别是心肌细胞和内皮细胞）的替代物。
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