Maintenance and propagation of mesenchymal stem cells

• US 8,084,023 B2
• Filed: 01/22/2007
• Issued: 12/27/2011
• Est. Priority Date: 01/22/2007
• Status: Active Grant

• Current Assignee: US Department of Veterans Affairs (Government of the United States of America), The Board of Trustees of the University of Arkansas (University of Arkansas System)
• Original Assignee: US Department of Veterans Affairs (Government of the United States of America), The Board of Trustees of the University of Arkansas (University of Arkansas System)
• Inventors: Chen, Xiao-Dong, Jilka, Robert L.
• Primary Examiner(s): Long, Scott
• Application Number:
  US11/625,763
• Publication Number:
  US 20080175816A1
• Time in Patent Office: 1,800 Days
• Field of Search: None
• US Class Current: 424/93.1
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• 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: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: C12M 21/08 for producing artificial tissue or for ex-vivo cultivation of tissue prostheses A61F2/00, grafts A61L27/00
• CPC Class Codes: C12M 25/14 Scaffolds; Matrices in general C12N5/0068
• CPC Class Codes: C12N 2513/00 3D culture
• CPC Class Codes: C12N 2533/90 Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
• CPC Class Codes: C12N 5/0662 Stem cells
• CPC Class Codes: C12N 5/0663 Bone marrow mesenchymal stem cells (BM-MSC)
• CPC Class Codes: C12N 5/0668 Mesenchymal stem cells from other natural sources

Abstract

Various embodiments of the present invention include compositions, materials and methods for maintaining and propagating mammalian mesenchymal stem cells in an undifferentiated state in the absence of feeder cells and applications of the same.

Claims

1. A cellular composition comprising a proliferating, undifferentiated mammalian mesenchymal stem cell embedded in a stromal cell-derived 3D extracellular matrix, wherein the stromal cell-derived 3D extracellular matrix comprises collagen I, collagen III, syndecan-1, perlecan, fibronectin, laminin, biglycan, and decorin.

2. The cellular composition of claim 1, wherein the cellular composition is essentially free of feeder cells.

3. The cellular composition of claim 1, wherein the mammalian mesenchymal stem cell is selected from the group consisting of a human mesenchymal stem cell and a murine mesenchymal stem cell.

4. The cellular composition of claim 1, wherein the mammalian mesenchymal stem cell is capable of symmetrical division.

5. The cellular composition of claim 1, wherein the stromal cell-derived 3D extracellular matrix is a marrow stromal cell derived extracellular matrix.

6. The cellular composition of claim 5, wherein the marrow stromal cell derived 3D extracellular matrix is manufactured by culturing marrow stromal cells, lysing the marrow stromal cells and removing the lysed marrow stromal cells by washing.