Selective elimination of tumorigenic cells from mixed culture of normal and tumorigenic cells using hybrid liposomes aimed at realizing of cell therapy

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-02-13 DOI:10.1007/s10616-023-00613-y

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Abstract

While induced pluripotent stem (iPS) cells are expected to be a cell source for regenerative medicine, they also have tumorigenic properties owing to their proliferative potential. During the manufacturing of regenerative medicine products, undifferentiated iPS cells and malignant transformed cells may be mixed in the cell culture population. Therefore, it is essential to eliminate tumorigenic cells selectively. In this study, a mixed culture of normal human fetal hepatocytes (Hc cells) and human hepatocellular carcinoma cells (HuH-7 cells) was used as a cell population model to be used as regenerative medicine products, and the selective elimination of HuH-7 cells by hybrid liposomes (HL) was analyzed. HL tended to fuse and accumulate more in HuH-7 cells due to larger fluidity of plasma membrane for HuH-7 cells than that for Hc cells. In a mixed culture of Hc and HuH-7 cells, HL selectively eliminated HuH-7 cells while allowing Hc cells to remain viable. In addition, HL treatment for the mixed culture of Hc and HuH-7 cells suppressed the tumorigenicity of HuH-7 cells. Therefore, HL selectively fused and accumulated in tumorigenic cells in a mixed cell culture of normal and tumorigenic cells, and eliminated tumorigenic cells while allowing normal cells to remain viable. The results of this study suggest the potential of HL in eliminating tumorigenic cells during the manufacturing of regenerative medicine products. Thus, HL could be expected to contribute to the development of safe regenerative medical products.

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利用旨在实现细胞疗法的混合脂质体，从正常细胞和致瘤细胞的混合培养液中选择性清除致瘤细胞

摘要尽管诱导多能干细胞（iPS）有望成为再生医学的细胞来源，但由于其增殖潜力，它们也具有致瘤特性。在再生医学产品的生产过程中，细胞培养群体中可能会混入未分化的 iPS 细胞和恶性转化细胞。因此，必须有选择性地消除致瘤细胞。本研究以正常人胎儿肝细胞（Hc 细胞）和人肝癌细胞（HuH-7 细胞）的混合培养作为细胞群模型，分析了杂交脂质体（HL）对 HuH-7 细胞的选择性清除作用。由于HuH-7细胞的质膜流动性比Hc细胞大，因此HL在HuH-7细胞中更容易融合和聚集。在 Hc 和 HuH-7 细胞的混合培养中，HL 可选择性地消除 HuH-7 细胞，而让 Hc 细胞保持活力。此外，对 Hc 和 HuH-7 细胞的混合培养进行 HL 处理可抑制 HuH-7 细胞的致瘤性。因此，在正常细胞和致瘤细胞的混合细胞培养中，HL可选择性地融合并积聚在致瘤细胞中，在消除致瘤细胞的同时使正常细胞保持活力。这项研究结果表明，在再生医学产品的生产过程中，HL 有可能消除致瘤细胞。因此，HL有望为开发安全的再生医学产品做出贡献。

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