Cartilage and bone repair and regeneration using postpartum-derived cells
Cells derived from postpartum tissue and methods for their isolation and induction to differentiate to cells of a chondrogenic or osteogenic phenotype are provided by the invention. The invention further provides cultures and compositions of the postpartum-derived cells and products related thereto. The postpartum-derived cells of the invention and products related thereto have a plethora of uses, including but not limited to research, diagnostic, and therapeutic applications, for example, in the treatment of bone and cartilage conditions.
1. A method of forming cartilage in a patient, said method comprising administering to said patient a matrix comprising a homogeneous population of undifferentiated umbilical cord tissue-derived cells, wherein the homogeneous population of cells is obtained from human postpartum umbilical cord substantially free of blood, and wherein said homogeneous population of cells:
i) exhibits increased expression, relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell, of an endogenous gene encoding interleukin 8 and an endogenous gene encoding reticulon 1;
ii) secretes MCP-1, IL-6, IL-8, GCP-2, HGF, KGF, FGF, HB-EGF, BDNF, TPO, MIP1b, RANTES and TIMP 1;
iii) produces CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, and HLA-A, B, C; and
iv) lacks production of CD31, CD34, CD117, CD141, and HLA-DR, DP, DQ,
whereby cartilage is formed in the matrix.
2. The method of claim 1 wherein said matrix is implanted into said patient.
3. The method of claim 1 wherein said matrix comprises at least one bioactive factor.
4. The method of claim 1 wherein said matrix is administered to a bone of said patient.
5. The method of claim 1 wherein said matrix is administered to cartilage of said patient.
6. The method of claim 1 wherein said homogeneous cell population is capable of self-renewal and expansion in culture, has the potential to differentiate into cells of a chondrogenic phenotype, and requires L-valine for growth.
7. The method of claim 1 wherein said homogeneous cell population has the potential for at least 40 doublings in culture.
8. The method of claim 1 wherein said homogeneous cell population does not express any of CD80, CD86, CD178, or HLA-G.
9. The method of claim 1 wherein said homogeneous cell population expresses a gene for each of chemokine (C-X-C motif) ligand 1(melanoma growth stimulating activity, alpha); chemokine (C-X-C motif) ligand 6 (granulocyte chemotactic protein 2); chemokine (C-X-C motif) ligand 3; and tumor necrosis factor, alpha-induced protein 3.
10. The method of claim 1 wherein said homogeneous cell population does not secrete any of the factors SDF-1alpha, TGF-beta2, ANG2, PDGFbb, MIP1a and VEGF.
11. The method of claim 1 wherein said homogeneous cell population is obtained by contacting umbilical cord tissue with an enzyme solution comprising a matrix metalloprotease, a neutral protease and a mucolytic enzyme.
12. A method of forming cartilage in a patient, said method comprising administering to said patient a matrix comprising a homogeneous population of undifferentiated umbilical cord tissue-derived cells, wherein said homogenous population of cells is deposited with ATCC under Accession No. PTA-6067, whereby cartilage is formed in the matrix.
13. A method of forming cartilage in a patient, said method comprising administering to said patient a matrix comprising a homogeneous population of undifferentiated umbilical cord tissue-derived cells, wherein said homogenous population of cells is deposited with ATCC under Accession No. PTA-6068, whereby cartilage is formed in the matrix.
14. The method of claim 12 , wherein the homogeneous population of undifferentiated umbilical cord tissue-derived cells has the potential to differentiate into cells of a chondrogenic phenotype.
15. The method of claim 13 , wherein the homogeneous population of undifferentiated umbilical cord tissue-derived cells has the potential to differentiate into cells of a chondrogenic phenotype.