Bone morphogenetic protein and fibroblast growth factor compositions and methods for the induction of cardiogenesis

• US 20050096274A1
• Filed: 09/28/2004
• Published: 05/05/2005
• Est. Priority Date: 04/07/1998
• Status: Abandoned Application

• Current Assignee: John W. Lough, Matthew R. Barron
• Original Assignee: John W. Lough, Matthew R. Barron
• Inventors: Barron, Matthew R., Lough, John W.
• Application Number:
  US10/951,396
• Publication Number:
  US 20050096274A1
• Time in Patent Office: Days
• US Class Current: 514/8.8
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/357 having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
• CPC Class Codes: A61K 38/1875 Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: C07K 14/51 Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor

Abstract

A composition comprising a purified mixture of a bone morphogenetic protein and a fibroblast growth factor is disclosed. In another embodiment, the present invention is a method of inducing cardiogenesis in cells of a non-cardiac lineage comprising the steps of exposing cells to the composition and observing the development of cardiac cells.

Claims

1. A composition comprising a purified mixture of a bone morphogenetic protein (BMP) and a fibroblast growth factor (FGF) selected from BMP-2 and FGF-2, BMP-4 and FGF-2, or BMP-4 and FGF-4.

2. The composition of claim 1, wherein the molar ratio of the BMP to the FGF is 1:

1.

3. The composition of claim 1, wherein the composition additionally comprises a matrix material.

4. The composition of claim 3, wherein the matrix material is collagen.

5. The composition of claim 1, wherein the composition comprises a purified mixture of BMP-2 and FGF-2.

6. The composition of claim 1, wherein the composition comprises a purified mixture of BMP-4 and FGF-2.

7. The composition of claim 1, wherein the composition comprises a purified mixture of BMP-4 and FGF-4.

8. A method for inducing cardiogenesis in cells of non-cardiac lineage, comprising the steps of:

exposing the cells to a purified mixture of a BMP and an FGF selected from BMP-2 and FGF-2, BMP-4 and FGF-2, or BMP-4 and FGF-4; and

observing the development of rhythmic and synchronously contractile cells.

10. The method of claim 8, wherein both the BMP and the FGF have a concentration from about 5 ng/ml to about 1,000 ng/ml.

11. The method of claim 8, wherein both the BMP and the FGF have a concentration of about 50 ng/ml.

12. The method of claim 8, wherein the exposure to the mixture of BMP and FGF is achieved by exogenously applying a mixture of the proteins to the cells.

13. The method of claim 8, wherein the exposure to the mixture of BMP and FGF is achieved by transforming the cells with a genetic construct encoding the BMP and the FGF.

14. The method of claim 8, wherein the exposure is in vivo.

15. The method of claim 8, wherein the exposure is in vitro.

16. The method of claim 8, wherein the cells are exposed to a purified mixture of BMP-2 and FGF-2.

9. The method of Claim8, further comprising the step of:

confirming the development of rhythmic and synchronously contractile cells by measuring the expression of sarcomeric α

-actin in the cells.

17. A method for inducing cardiogenesis in cells of non-cardiac lineage, comprising the steps of:

exposing the cells to a purified mixture of a BMP and an FGF selected from BMP-2 and FGF-2, BMP-4 and FGF-2, or BMP-4 and FGF-4; and

measuring the expression of SRF and Nkx-2.5 in the cells.

18. A method for inducing cardiogenesis in cells of non-cardiac lineage, sing the steps of:

exposing the cells to a purified mixture of a BMP and an FGF selected from and FGF-2, BMP-4 and FGF-2, or BMP-4 and FGF-4; and

continuing to expose the cells to the BMP without the FGF.