Cell Sheet Containing Mesenchymal Stem Cells

• US 20090053277A1
• Filed: 01/27/2006
• Published: 02/26/2009
• Est. Priority Date: 01/27/2005
• Status: Active Grant

• Current Assignee: H&L Medical Corporation
• Original Assignee: Japan Health Sciences Foundation
• Inventors: Nagaya, Noritoshi, Miyahara, Yoshinori, Mori, Hidero
• Granted Patent: US 9,782,439 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/3873 Muscle tissue, e.g. sphincter
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: C12N 2539/10 Coating allowing for selective detachment of cells, e.g. thermoreactive coating
• CPC Class Codes: C12N 5/0667 Adipose-derived stem cells [ADSC]; Adipose stromal stem cells

Abstract

Mesenchymal stem cells are pluripotent cells capable of differentiating into myocardial and vascular endothelial cells. The present invention demonstrates that the mesenchymal stem cell sheet have therapeutic potential for a severely damaged heart due to its pluripotency and in situ self-renewal capability. Mesenchymal stem cells derived from adipose tissue were cultured to prepare a mesenchymal stem cell sheet. Four weeks after induction of myocardial infarction in rats, the mesenchymal stem cell sheet was transplanted to the heart. The mesenchymal stem cell sheet were readily engrafted to the surface of the scarred myocardium, grew gradually in situ, and formed a thick layer (approximately 600 μm) in 4 weeks. The grown transplanted mesenchymal tissue contained newly formed blood vessels, myocardial cells, and undifferentiated mesenchymal cells. The engrafted mesenchymal stem cells inhibited thinning of the myocardial wall in the scar area, and improved cardiac function and survival rate in rats with myocardial infarcts. Thus, mesenchymal stem cell sheet transplantation may represent a novel therapeutic approach for myocardial tissue regeneration.

Claims

1. A cell sheet for transplantation comprising mesenchymal stem cells.

2. The cell sheet according to claim 1, wherein the stem cells are derived from bone marrow or adipose tissue.

3. The cell sheet according to claim 1, wherein the stem cells will grow in situ to form a layer with a thickness of 100 μ

m or more.

4. The cell sheet according to claim 1, wherein the stem cells will grow in situ to induce cardiac muscle and neovascularization.

5. The cell sheet according to claim 1, wherein the stem cells will differentiate in situ into myocardial, vascular endothelial, and vascular smooth muscle cells.

6. A method for treating heart failure in a patient, comprising transplanting a cell sheet for transplantation comprising mesenchymal stem cells to the heart of said patient.