Substrate Recognition By Differentiable Human Mesenchymal Stem Cells

• US 20100233807A1
• Filed: 04/20/2010
• Published: 09/16/2010
• Est. Priority Date: 12/03/2004
• Status: Abandoned Application

• Current Assignee: New Jersey Institute of Technology
• Original Assignee: New Jersey Institute of Technology
• Inventors: Arinzeh, Treena, Shanmugasundaram, Shobana, Jaffe, Michael
• Application Number:
  US12/763,755
• Publication Number:
  US 20100233807A1
• Time in Patent Office: Days
• US Class Current: 435/366
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/3633 Extracellular matrix [ECM]
• CPC Class Codes: A61L 27/3821 Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells
• CPC Class Codes: A61L 27/3852 Cartilage, e.g. meniscus
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C12M 25/14 Scaffolds; Matrices in general C12N5/0068
• CPC Class Codes: C12N 2506/1346 from mesenchymal stem cells
• CPC Class Codes: C12N 2533/40 Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 5/0654 Osteocytes, Osteoblasts, Odontocytes; Bones, Teeth
• CPC Class Codes: C12N 5/0655 Chondrocytes; Cartilage
• CPC Class Codes: C12N 5/0663 Bone marrow mesenchymal stem cells (BM-MSC)
• CPC Class Codes: D01D 5/0038 the fibre formed by solvent evaporation, i.e. dry electro-spinning
• CPC Class Codes: H03L 7/093 using special filtering or amplification characteristics in the loop H03L7/087 - H03L7/091 take precedence

Abstract

The invention described herein provides a structure for growing isolated differentiable human mesenchymal cells, which includes a three-dimensional matrix of fibers. The matrix serves as an implantable scaffolding for delivery of differentiable human mesenchymal cells in tissue engineering. The invention further provides compositions that contain the three-dimensional matrix of fibers seeded with isolated differentiable human mesenchymal cells, wherein the matrix forms a supporting scaffold for growing the isolated differentiable human mesenchymal cells, and wherein the differentiable human mesenchymal cells differentiate into a mature cell phenotype. The invention further provides methods of preparing the implantable nanofiber matrix scaffolding seeded with differentiable human mesenchymal cells for use in tissue engineering.

Claims

1. A structure for growing isolated differentiable human mesenchymal cells comprising a three-dimensional matrix of electrospun fibers, wherein the matrix of fibers is seeded with the isolated differentiable human mesenchymal cells, such that the isolated differentiable human mesenchymal cells attach to the matrix of fibers and proliferate on the matrix of fibers, and wherein the three-dimensional matrix of fibers forms a supporting scaffold of fibers for promoting differentiation of the isolated differentiable human mesenchymal cells into a mature cell phenotype on the scaffold of fibers.

2. The structure according to claim 1, wherein the three-dimensional matrix of fibers is formed of a polymeric material.

3. The structure according to claim 2, wherein the polymeric material is a biocompatible polymer.

5. The structure according to claim 3, wherein the biocompatible polymer is poly L-lactic acid.

6. The structure according to claim 1, wherein the electrospun fibers have a diameter of from about 1 nm to about 100 μ

m.

7. The structure according to claim 1, wherein the electrospun fibers have a diameter of from about 300 nm to about 30 μ

m.

8. The structure according to claim 1, wherein the isolated differentiable human mesenchymal cells are isolated from human bone marrow.

9. The structure according to claim 1, wherein the isolated differentiable human mesenchymal cells have a CD44⁺, CD34⁻

, CD45⁻

phenotype.

10. The structure according to claim 1, wherein the seeded isolated differentiable human mesenchymal cells are capable of growth throughout the scaffold.

11. The structure according to claim 1, wherein the mature cell phenotype comprises a chondrogenic cell phenotype.

12. A composition for use in tissue engineering comprising:

isolated differentiable human mesenchymal cells; and

a supporting scaffold for growing the isolated differentiable human mesenchymal cells, the supporting scaffold comprising a three-dimensional matrix of electrospun fibers, wherein the matrix is seeded with the isolated differentiable human mesenchymal cells, wherein the isolated differentiable human mesenchymal cells attach to the matrix of fibers, proliferate on the matrix of fibers, such that the isolated differentiable human mesenchymal cells attach to the matrix of fibers and proliferate on the matrix of fibers, and wherein the supporting scaffold of fibers promotes differentiation of the isolated differentiable human mesenchymal cells into a mature cell phenotype on the scaffold of fibers.

13. The composition according to claim 12, wherein the three dimensional matrix of fibers is formed of a polymeric material.

14. The composition according to claim 13, wherein the polymeric material is a biocompatible polymer.

15. The composition according to claim 14, wherein the biocompatible polymer is poly L-lactic acid.

16. The composition according to claim 12, wherein the differentiable human mesenchymal cells are isolated from human bone marrow.

17. The composition according to claim 12, wherein the isolated differentiable human mesenchymal cells have a CD44⁺, CD34⁻

, CD45⁻

phenotype.

18. The composition according to claim 12, wherein the seeded differentiable human mesenchymal cells are capable of growth throughout the scaffold.

19. The composition according to claim 12, wherein the mature cell phenotype comprises a chondrogenic cell phenotype.

20. The structure according to claim 12, wherein the electrospun fibers have a diameter of from about 1 nm to about 100 μ

m.