Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Adv Drug Deliv Rev. 2019 Jan 1;138:276-292. doi: 10.1016/j.addr.2019.01.004. Epub 2019 Jan 11.
Cell transplantation is a promising approach for promoting tissue regeneration in the treatment of damaged tissues or organs. Although cells have conventionally been delivered by direct injection to damaged tissues, cell injection has limited efficiency to deliver therapeutic cells to the target sites. Progress in tissue engineering has moved scaffold-based cell/tissue delivery into the mainstream of tissue regeneration. A variety of scaffolds can be fabricated from natural or synthetic polymers to provide the appropriate culture conditions for cell growth and achieve in-vitro tissue formation. Tissue engineering has now become the primary approach for cell-based therapies. However, there are still serious limitations, particularly for engineering of cell-dense tissues. "Cell sheet engineering" is a scaffold-free tissue technology that holds even greater promise in the field of tissue engineering and regenerative medicine. Thermoresponsive poly(N-isopropylacrylamide)-grafted surfaces allow the fabrication of a tissue-like cell monolayer, a "cell sheet", and efficiently delivers this cell-dense tissue to damaged sites without the use of scaffolds. At present, this unique approach has been applied to human clinical studies in regenerative medicine. Furthermore, this thermally triggered cell manipulation system allows us to produce various types of 3D tissue models not only for regenerative medicine but also for tissue modeling, which can be used for drug discovery. Here, new cell sheet-based technologies are described including vascularization for scaled-up 3D tissue constructs, induced pluripotent stem (iPS) cell technology for human cell sheet fabrication and microfabrication for arranging tissue microstructures, all of which are expected to produce more complex tissues based on cell sheet tissue engineering.
细胞移植是一种很有前途的方法，可以促进组织再生，从而治疗受损组织或器官。虽然传统上细胞是通过直接注射到受损组织来输送的，但细胞注射在将治疗细胞输送到靶位方面效率有限。组织工程学的进展已经将基于支架的细胞/组织输送推向了组织再生的主流。各种支架可以由天然或合成聚合物制成，为细胞生长提供适当的培养条件，并实现体外组织形成。组织工程学现在已经成为细胞治疗的主要方法。然而，仍然存在严重的限制，特别是对于细胞密集组织的工程。“细胞片工程”是一种无支架组织技术，在组织工程和再生医学领域具有更大的潜力。温敏性聚（N-异丙基丙烯酰胺）接枝表面允许制造类似组织的单层细胞，即“细胞片”，并且可以在不使用支架的情况下将这种细胞密集的组织有效地输送到受损部位。目前，这种独特的方法已经应用于再生医学的人体临床研究。此外，这种热触发的细胞操作系统允许我们不仅为再生医学，而且为组织建模生产各种类型的 3D 组织模型，这可用于药物发现。在这里，描述了新的基于细胞片的技术，包括用于放大 3D 组织构建体的血管化、用于制造人细胞片的诱导多能干细胞（iPS）技术以及用于组织微结构排列的微加工，所有这些都有望基于细胞片组织工程产生更复杂的组织。
