Soft tissue repair and regeneration using postpartum-derived cells
First Claim
Patent Images
1. A postpartum-derived cell (PPDC) comprising a cell derived from human postpartum tissue substantially free of blood, wherein said PPDC self-renews and expands in culture;
- wherein said PPDC provides trophic support to a soft tissue cell;
wherein said cell requires L-valine for growth;
wherein said cell grows in about 5% to about 20% oxygen;
wherein said cell 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, CD 117, 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 MCP-1, IL-6, IL-8, GCP-2, HGF, KGF, FGF, HB-EGF, BDNF, TPO, MIP1a, RANTES, and TIMP1;
(h) lack of secretion of at least one of TGF-beta2, ANG2, PDGFbb, MIP1b, 1309, MDC, and VEGF, as detected by ELISA; and
(i) the ability to undergo at least 40 population doublings in culture.
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Abstract
Cells derived from postpartum tissue having the potential to support cells of and/or differentiate to cells of a soft tissue lineage, and methods of preparation and use of those postpartum tissue-derived cells, are provided by the invention. The invention also provides methods for the use of such postpartum-derived cells and products related thereto in therapies for conditions of soft tissue.
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Citations
113 Claims
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1. A postpartum-derived cell (PPDC) comprising a cell derived from human postpartum tissue substantially free of blood, wherein said PPDC self-renews and expands in culture;
- wherein said PPDC provides trophic support to a soft tissue cell;
wherein said cell requires L-valine for growth;
wherein said cell grows in about 5% to about 20% oxygen;
wherein said cell 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, CD 117, 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 MCP-1, IL-6, IL-8, GCP-2, HGF, KGF, FGF, HB-EGF, BDNF, TPO, MIP1a, RANTES, and TIMP1;
(h) lack of secretion of at least one of TGF-beta2, ANG2, PDGFbb, MIP1b, 1309, MDC, and VEGF, as detected by ELISA; and
(i) the ability to undergo at least 40 population doublings in culture. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113)
- wherein said PPDC provides trophic support to a soft tissue cell;
Specification