Myocardial cells stop their proliferation upon the maturation of a host. Accordingly, restoration of myocardial cells could not be expected in a heart that has been once afflicted with myocardial infarction, and the heart was considered to be a nonregenerative organ. In recent years, however, the existence of myocardial precursor/stem cells was discovered in the heart, and division thereof or differentiation thereof into myocardial cells was occasionally observed (Beltrami A. P., et al., “Adult Cardiac Stem Cells Are Multipotent and Support Myocardial Regeneration,” Cell, Vol. 114, pp. 763-776, 2003). The development of a technique for inducing ectopic cells, which can be differentiated into myocardial cells, to differentiate into myocardial cells enables the treatment of myocardial infarction, which was difficult in the past.
Master cells of the fetal period, i.e., embryonic stem cells (ES cells), can be easily differentiated into myocardial cells. However, preparation of ES cells for each patient is ethically problematic, and myocardial cells differentiated from the randomly prepared ES cells cause immunological rejection. Thus, ES cells cannot be applied to actual medical practice at present.
The bone marrow stroma comprises multipotent mesenchymal stem cells, and many reports have been heretofore made concerning tissue regeneration techniques utilizing such mesenchymal stem cells. Examples of such techniques include: the regeneration of skeletal muscles utilizing bone marrow-derived myocytes (Ferrari G. et al., “Muscle regeneration by bone marrow-derived myogenic progenitors,” Science 1998, 279 (5356), pp. 1528-30); the improvement in cardiac functions via administration of c-kit-positive bone marrow stem cells to the heart (Orlic D, et al., “Bone marrow cells regenerate infracted myocardium,” Nature, Vol. 410, No. 5, 2001, pp. 701-705); and the regeneration of cardiac muscles mediated by bone marrow-derived cells (JP Patent Publication (Kohyo) No. 2002-511094 A, WO 01/048151, and JP Patent Publication (Kohyo) No. 2002-521493 A). It is also reported that the mesenchymal stem cells can be differentiated into myocardial cells by adding a demethylating enzyme to the mesenchymal stem cells to reset them (Makino S. et al., “Cardiomyocytes can be generated from marrow stromal cells in vitro,” The Journal of Clinical Investigation 103: pp. 697-705, 1999). The myocardial cells prepared via such method have been subjected to demethylation, and thus, they may cause anomalies in the future. Accordingly, clinical application of such myocardial cells would involve considerable difficulties.
Tissue regeneration utilizing mesenchymal stem cells involves the issue of quantitative limitations of the bone marrow to be used, and more extensive resources have been expected for materials for tissue regeneration. Fat tissues are easily obtainable. Multipotent cells have been isolated from human fat tissues, and differentiation thereof into nerve cells was recently observed (Zuk P. A. et al., “Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based Therapies,” Tissue Engineering, Vol. 7, No. 2, 2001, pp. 211-228; Zuk P. A. et al., “Human Adipose Tissue Is a Source of Multipotent Stem Cells,” Molecular Biology of the Cell, Vol. 13, pp. 4279-4295, 2002). Also, mouse cell strains derived from sarcoblasts that can be differentiated into myocardial cells have also been isolated (JP Patent Publication (Kokai) No. 2003-325169 A and 2003-259863 A). Use of such cells is not practical because of their particularity and the need for a complicated step of culture in order to induce cell differentiation.