1. Field of the Invention
The present invention relates to a cell structure and a method for producing a cell structure. Specifically, the present invention relates to a cell structure which can form a blood vessel after transplantation, and a production method thereof.
2. Description of the Related Art
Currently, regenerative medicine, which regenerates living body tissues and organs having functional disorders or dysfunction, is put into practical use. The regenerative medicine is new medical technology creating a form or a function of a living body tissue that cannot be recovered with only natural healing ability possessed by a living body, which is the same as that of an original tissue, again, using three factors including a cell, a scaffold, and a growth factor. In recent years, treatment using cells is gradually realized. Examples thereof include cartilage treatment using autologous chondrocytes, and cultured epidermis using autologous cells; bone regeneration treatment using mesenchymal stem cells; myocardial cell sheet treatment using myoblasts; cornea regeneration treatment using corneal epithelial sheets; and nerve regeneration treatment. These kinds of new treatment are different from alternative medicine (for example, a bone prosthetic material or hyaluronic acid injection) using an artifact in the related art, and repair and regenerate biological tissues, thereby obtaining a high treatment effect. Actually, products such as cultured epidermis or cultured cartilage using autologous cells have been available on the market.
For example, when regenerating the myocardium using cell sheets, it is considered that a multilayer structure of the cell sheets is required in order to regenerate a tissue with thickness. In recent years, Okano et al. have developed a cell sheet using a temperature-responsive culture dish. Since the cell sheet does not require enzymatic treatment using trypsin or the like, bonding between cells and adhesive proteins are maintained (Shimizu, T. et al., Circ. Res. 90, e40-48 (2002), Kushida, A. et al., J. Biomed. Mater. Res. 51, 216-223 (2000), Kushida, A. et al., J. Biomed. Mater. Res. 45, 355-362 (1999), Shimizu, T., Yamato, M., Kikuchi, A. & Okano, T., Tissue Eng. 7, 141-151 (2001), Shimizu, T et al., J. Biomed. Mater. Res. 60, 110-117(2002), and Harimoto, M. et al., J. Biomed. Mater. Res. 62, 464-470 (2002)). It is anticipated that a technology for producing such a cell sheet will be useful for regeneration of myocardial tissues (Shimizu, T., Yamato, M., Kikuchi, A. & Okano, T., Biomaterials 24, 2309-2316 (2003)). In addition, Okano et al. have developed a cell sheet in which it is necessary to form a vascular plexus and to which vascular endothelial cells are introduced together (Inflammation and Regeneration vol. 25 No. 3 2005, p 158-159. The 26th Annual Meeting of the Japanese Society of Inflammation and Regeneration, “Fusion of Inflammation and Regeneration Researches”, Teruo OKANO).
In addition, a cell structure, which contains cells and macromolecular blocks having biocompatibility, and in which the plurality of the above-described macromolecular blocks are arranged in gaps between the plurality of the above-described cells, is disclosed in WO2011/108517A. In the cell structure disclosed in WO2011/108517A, it is possible to deliver nutrients to the inside of the cell structure from the outside. The cell structure has a sufficient thickness, and cells exist in the structure uniformly. In Example of WO2011/108517A, high cell survival activity is verified using a macromolecular block formed of a recombinant gelatin material or a natural gelatin material. A cell structure for cell transplantation, which contains a macromolecular block having biocompatibility and at least one kind of cell, and in which the plurality of the above-described macromolecular blocks are arranged in the gaps between the plurality of the above-described cells, is disclosed in JP2014-12114A. In Example of JP2014-12114A, angiogenesis is evaluated using the cell structure for cell transplantation.