Cartilage and bone repair and regeneration using postpartum-derived cells
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Abstract
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.
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Citations
87 Claims
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1-85. -85. (canceled)
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86. A conditioned medium generated by the growth of a culture of cells in a culture medium wherein said culture of cells comprises at least one postpartum-derived cell (PPDC) wherein said PPDC is derived from human postpartum tissue substantially free of blood, wherein said PPDC is capable of self-renewal and expansion in culture and has the potential to differentiate into a cell of an osteogenic or chondrogenic phenotype;
- wherein said PPDC requires L-valine for growth;
wherein said PPDC is capable of growth in about 5% to about 20% oxygen;
wherein said PPDC further comprises at least one of the following characteristics;
(a) production of at least one of granulocyte chemotactic protein 2 (GCP-2), reticulon 1, tissue factor, vimentin, and alpha-smooth muscle actin;
(b) lack of production of at least one of GRO-alpha or oxidized low density lipoprotein receptor, as detected by flow cytometry;
(c) production of at least one of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A,B,C;
(d) lack of production of at least one of CD31, CD34, CD45, CD80, CD86, CD117, CD141, CD178, B7-H2, HLA-G, and HLA-DR,DP,DQ, as detected by flow cytometry;
(e) expression, which relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an ileac crest bone marrow cell, is increased for at least one of interleukin 8;
reticulon 1;
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 or expression, which relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an ileac crest bone marrow cell, is increased for at least one of C-type lectin superfamily member A2, Wilms tumor 1, aldehyde dehydrogenase 1 family member A2, renin, oxidized low density lipoprotein receptor 1, protein kinase C zeta, clone IMAGE;
4179671, hypothetical protein DKFZp564F013, downregulated in ovarian cancer 1, and clone DKFZp547K1113;
(f) expression, which relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an ileac crest bone marrow cell, is reduced for at least one of;
short stature homeobox 2;
heat shock 27 kDa protein 2;
chemokine (C—
X—
C motif) ligand 12 (stromal cell-derived factor
1);
elastin;
cDNA DKFZp586M2022 (from clone DKFZp586M2022);
mesenchyme homeobox 2;
sine oculis homeobox homolog 1;
crystallin, alpha B;
dishevelled associated activator of morphogenesis 2;
DKFZP586B2420 protein;
similar to neuralin 1;
tetranectin;
src homology three (SH3) and cysteine rich domain;
B-cell translocation gene 1, anti-proliferative;
cholesterol 25-hydroxylase;
runt-related transcription factor 3;
hypothetical protein FLJ23191;
interleukin 11 receptor, alpha;
procollagen C-endopeptidase enhancer;
frizzled homolog 7;
hypothetical gene BC008967;
collagen, type VIII, alpha 1;
tenascin C;
iroquois homeobox protein 5;
hephaestin;
integrin, beta 8;
synaptic vesicle glycoprotein 2;
cDNA FLJ12280 fis, clone MAMMA1001744;
cytokine receptor-like factor 1;
potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4;
integrin, alpha 7;
DKFZP586L151 protein;
transcriptional co-activator with PDZ-binding motif (TAZ);
sine oculis homeobox homolog 2;
KIAA1034 protein;
early growth response 3;
distal-less homeobox 5;
hypothetical protein FLJ20373;
aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II);
biglycan;
fibronectin 1;
proenkephalin;
integrin, beta-like 1 (with EGF-like repeat domains);
cDNA clone EUROIMAGE 1968422;
EphA3;
KIAA0367 protein;
natriuretic peptide receptor C/guanylate cyclase C (atrionatriuretic peptide receptor C);
hypothetical protein FLJ14054;
cDNA DKFZp564B222 (from clone DKFZp564B222);
vesicle-associated membrane protein 5;
EGF-containing fibulin-like extracellular matrix protein 1;
BCL2/adenovirus E1B 19 kDa interacting protein 3-like;
AE binding protein 1;
cytochrome c oxidase subunit VIIa polypeptide 1 (muscle);
neuroblastoma, suppression of tumorigenicity 1; and
insulin-like growth factor binding protein 2, 36 kDa;
(g) secretion of at least one of monocyte chemotactic protein-1, interleukin(IL)-6, IL-8, granulocyte chemotactic protein-2, hepatocyte growth factor, keratinocyte growth factor, fibroblast growth factor, heparin binding-epidermal growth factor, brain derived neurotrophic factor, thrombopoietin, macrophage inflammatory protein (MIP)-1a, RANTES, and tissue inhibitor of matrix metalloprotease 1;
(h) lack of secretion of at least one of transforming growth factor-beta2, angiopoetin-2, platelet derived growth factor-bb, MIP 1b, I309, macrophage-derived chemokine, and vascular endothelial growth factor, as detected by ELISA; and
(i) the ability to undergo at least 40 population doublings in culture.
- wherein said PPDC requires L-valine for growth;
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87-108. -108. (canceled)
Specification