1. Field of the Invention
The present invention relates to cultivation of a cell or tissue in the fields of regeneration medicine and tissue engineering, and relates to a method of three dimensional tissue cultivation for three dimensional tissue or organ regeneration. Concretely, the present invention relates to a cultivation apparatus and a cultivation method that are used in cultivation executed with one or some of a cell, a cell scaffold and an ECM (extracellular matrix) that a cell generates, as a cell construct. There may be a case where the above cultivation is executed with addition of a culture fluid, other additives, a growth factor, a chemical and so on.
In short, the cultivation apparatus and the cultivation method of the present invention differ from the conventional static cultivation. The cultivation apparatus and the cultivation method of the present invention are an apparatus relating to three dimensional cultivation where physical action is used together. The cultivation apparatus is for realizing objective regeneration tissue by promotion of differentiation or stop thereof along with growth, cell migration and substance migration that are promoted by stimulating a cell of a cell construct aggressively and displacing a cell construct.
2. Description of the Related Art
For cultivation of a cell or tissue, a method of imparting physical stimulation such as pressure and tension to a cell or tissue to be cultivated is studied, and various bioreactors and so on are suggested. Two dimension cultivation (plane cultivation) is a cultivation method using a flat bottomed culture carrier, and in general, is static cultivation in an incubator. Suspension cultivation is a method of cultivating a non-adherent cell being suspended. This method is also static cultivation in an incubator. Three dimension cultivation is a method that is generally executed such that a cell scaffold where a cell is disseminated is left still in an incubator to be cultivated. It is general for the three dimension cultivation (using a bioreactor) that a cell is made to adhere to or is enclosed by a cell scaffold to process stirring of a culture fluid and so on. It is conceived that in the three dimension cultivation of a cell scaffold, physical action such as pressure, compression, tension and shear are imparted to a cell.
A cultivation apparatus for imparting physical action is called “a bioreactor”, “a tissue engineering processor”, etc. Such apparatus is expected to be into practical utilization as a cell/tissue cultivation apparatus in vitro for cultivation experiments of tissue engineering and regeneration medicine.
Concerning such bioreactor having functions of cultivating a cell or tissue, and imparting physical displacement, stress and stimulation used in the cultivation, a method for cultivating a cell or tissue and an apparatus therefor are disclosed in Japanese Laid-open Patent Publication No. 2001-238663 (Abstract, etc.) as an example of using pressure and oscillation (supersonic wave), a method for in vivo, ex vivo and in vitro, repair and regeneration of cartilage and collagen, and bone remodeling is disclosed in Published Japanese Translations of PCT International Publication for Patent Application No. 2004-512031 (Abstract, etc.) as an example of using pressure, a cell and tissue-cultivating apparatus is disclosed in Japanese Laid-open Patent Publication No. 2002-315566 (Abstract, etc.) as an example of using shear force, a cell and tissue-cultivating device is disclosed in Japanese Laid-open Patent Publication No. 2003-061642 (Abstract, etc.) as an example of using tensile force, a cell and tissue cultivation apparatus is disclosed in Japanese Laid-open Patent Publication No. 2003-180331 (Abstract, etc.) as an example of using compression force, a device for cultivating cell is disclosed in Japanese Laid-open Patent Publication No. H09-313166 (Abstract, etc.) as an example of using shear force, a loading device of extending and contracting stimulation for cultivating a cell by using a silicone belt is disclosed in Japanese Laid-open Patent Publication No. H10-155475 (Abstract, etc.) as an example of using tensile force, and an apparatus executing sterilization, inoculation, cultivation, preservation, transport and test of tissue and a synthetic or natural vascular graft, and a method therefor are disclosed in Published Japanese Translations of PCT International Publication for Patent Application No. H11-504216 (Abstract, etc.) as an example of using both tension and shear. A cultivation method where distortion is given to cells held on membranes by the membranes is disclosed in Japanese Laid-open Patent Publication No. 2005-143343 (Abstract, etc.). A semi-permeable membrane being used for cultivation is disclosed in International Publication Pamphlet No. WO 2006/015304 A2 (Abstract, etc.) and Published Japanese Translations of PCT International Publication for Patent Application No. 2000-513214 A (Abstract, etc.). Imparting of various kinds of physical action and stimulation, and using of a semi-permeable membrane are tried for cultivation of a cell, etc.
There are regions receiving many kinds of stress in the human body. Tissue used for repairing these regions is different according to the regions. For example, a disc, a meniscus, a bone, fiber cartilage and a valve of a heart receive bending force in vivo. This bending stress is different from simple pressure, compression, tension, shear, etc. It is insufficient that tissue cultivated by a stimulus factor such as a simple pressure, compression, tension and shear is applied to a region receiving such bending force.
For the above, the inventors of the present invention conceive that bending is so useful for growth, etc. of a cell or tissue as stimulation or a load imparted to a cell or tissue to be cultivated. Such problem is not disclosed in the above patent documents, and is not also suggested therein.