Derivation of fibrochondrocytes from progenitor cells

Patent metadata

Field	Value
Publication number	US-9487754-B2
Application number	US-201113877260-A
Country	US
Kind code	B2
Filing date	Oct 3, 2011
Priority date	Oct 1, 2010
Publication date	Nov 8, 2016
Grant date	Nov 8, 2016

Abstract

Provided herein are compositions and methods for forming fibrochondrocytes or fibrochondrocyte-like cells from progenitor cells, such as mesenchymal stem cells. One aspect provides a fibrochondrocyte culture medium including CTGF and TGFβ3, optionally encapsulated by microspheres having different release profiles. Another aspect provides a method for forming fibrochondrocytes or fibrochondrocyte-like cells from progenitor cells by culturing with CTGF and TGFβ3.

First claim

What is claimed is:

1. A method of treating a subject having a meniscus tissue defect, the method comprising:
(a) implanting into a subject in need thereof, at a site of a meniscus tissue defect, a scaffold comprising
(i) an anatomically correct model of a meniscus,
(ii) connective tissue growth factor (CTGF) encapsulated in a first microsphere in an outer region of the scaffold, and
(iii) transforming growth factor β3 (TGFβ3) encapsulated in a second microsphere in an inner region of the scaffold;

(b) inducing migration of a progenitor cell into or onto the scaffold;
(c) forming chondrocytes or chondrocyte-like cells in the inner region of the meniscus shaped scaffold; and
(d) forming fibroblasts or fibroblast-like cells in the outer region of the meniscus shaped scaffold,
wherein
the first microsphere releases CTGF before the second microsphere releases TGFβ3, and
the scaffold does not comprise a transplanted cell prior to implant.

2. The method of claim 1 , wherein the scaffold comprises a biocompatible matrix material.

3. The method of claim 1 , wherein the scaffold comprises poly(lactic-co-glycolic acid) (PLGA) or polycaprolactone (PCL).

4. The method of claim 1 , wherein the scaffold comprises at least one physical channel.

5. The method of claim 1 , wherein the scaffold is an anatomically correct model of a knee meniscus.

6. The method of claim 1 , wherein the scaffold further comprises:
a fibroblastic induction supplement comprising ascorbic acid; or
a chondrogenic induction supplement comprising one or more of ITS+1 solution, sodium pyruvate, ascorbic acid 2-phosphate, proline, or dexamethasone.

7. The method of claim 1 , wherein CTGF has a concentration of about 10 to about 1000 ng/mL; and TGFβ3 has a concentration of about 1 to about 1000 ng/mL.

8. The method of claim 1 , wherein CTGF has a concentration of about 100 ng/mL; and TGFβ3 has a concentration of about 10 ng/mL.

9. The method of claim 1 , wherein the first microsphere is a 50:50 poly(lactic-co-glycolic acid) (PLGA) microsphere and the second microsphere is a 75:25 PLGA microsphere.

10. The method of claim 1 , wherein the number of formed fibrochondrocytes or fibrochondrocyte-like cells in the scaffold is at least about 100% greater than the number of fibrochondrocytes or fibrochondrocyte-like cells formed under conditions not comprising CTGF and TGFβ3.

11. The method of claim 1 , wherein the fibrochondrocytes or fibrochondrocyte-like cells display one or more of: increased collagen (COL) deposition; increased proteoglycan (PG) deposition; increased glycosaminoglycan (GAG) deposition; increased proCOL-I+; or increased proCOL-IIα+, as compared to the progenitor cell.

12. The method of claim 1 , wherein the progenitor cell is a mesenchymal stem cell.

13. The method of claim 1 , wherein the progenitor cell is a human mesenchymal stem cell.

14. The method of claim 1 , wherein the first microsphere releases CTGF faster than the second microsphere releases TGFβ3.

Assignees

• Mao Jeremy J
• Lee Chang Hun
• Univ Columbia

Inventors

• Mao Jeremy J
• Lee Chang Hun

Classifications

• A61L27/18

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds · CPC title

• A61L2300/414

  Growth factors · CPC title

• A61L27/54 Primary

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• C12N5/0655 Primary

  Chondrocytes; Cartilage · CPC title

• C12N2533/40

  Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers · CPC title