Treatment of stroke and other acute neuraldegenerative disorders using postpartum derived cells
First Claim
1. A method of treating a patient having an acute neurodegenerative condition, the method comprising administering to the patient postpartum-derived cells in an amount effective to treat the neurodegenerative condition, wherein the postpartum-derived cells are derived from human placental or umbilical cord tissue substantially free of blood, wherein the cells are capable of self-renewal and expansion in culture and have the potential to differentiate into cells of at least a neural phenotype;
- wherein the cells require L-valine for growth and can grow in at least about 5% oxygen;
wherein the cells further comprise at least one of the following characteristics;
a) potential for at least about 40 doublings in culture;
b) attachment and expansion on a coated or uncoated tissue culture vessel, wherein the coated tissue culture vessel comprises a coating of gelatin, laminin, collagen, polyomithine, vitronectin, or fibronectin;
c) production of at least one of tissue factor, vimentin, and alpha-smooth muscle actin;
d) production of at least one of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A, B, C;
e) 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;
f) expression of a gene, 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 a gene encoding;
interleukin 8;
reticulon 1;
chemokine (C-X-C motif) ligand 1 (melonoma growth stimulating activity, alpha);
chemokine (C-X-C motif) ligand 6 (granulocyte chemotactic protein
2);
chemokine (C-X-C motif) ligand 3;
tumor necrosis factor, alpha-induced protein 3;
C-type lectin superfamily member 2;
Wilms tumor 1;
aldehyde dehydrogenase 1 family member A2;
renin;
oxidized low density lipoprotein receptor 1;
Homo sapiens clone IMAGE;
4179671;
protein kinase C zeta;
hypothetical protein DKFZp564F013;
downregulated in ovarian cancer 1; and
Homo sapiens gene from clone DKFZp547k1113. g) expression of a gene, 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 a gene encoding;
short stature homeobox 2;
heat shock 27 kDa protein 2;
chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor
1);
elastin (supravalvular aortic stenosis, Williams-Beuren syndrome);
Homo sapiens mRNA;
cDNA DKFZp586M2022 (from clone DKFZp586M2022);
mesenchyme homeo box 2 (growth arrest-specific homeo box);
sine oculis homeobox homolog 1 (Drosophila);
crystallin, alpha B;
disheveled associated activator of morphogenesis 2;
DKFZP586B2420 protein;
similar to neuralin 1;
tetranectin (plasminogen binding protein);
src homology three (SH3) and cysteine rich domain;
cholesterol 25-hydroxylase;
runt-related transcription factor 3;
interleukin 11 receptor, alpha;
procollagen C-endopeptidase enhancer;
frizzled homolog 7 (Drosophila);
hypothetical gene BC008967;
collagen, type VIII, alpha 1;
tenascin C (hexabrachion);
iroquois homeobox protein 5;
hephaestin;
integrin, beta 8;
synaptic vesicle glycoprotein 2;
neuroblastoma, suppression of tumorigenicity 1;
insulin-like growth factor binding protein 2, 36 kDa;
Homo sapiens cDNA FLJ12280 fis, clone MAMMA1001744;
cytokine receptor-like factor 1;
potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4;
integrin, beta 7;
transcriptional co-activator with PDZ-binding motif (TAZ);
sine oculis homeobox homolog 2 (Drosophila);
KIAA1034 protein;
vesicle-associated membrane protein 5 (myobrevin);
EGF-containing fibulin-like extracellular matrix protein 1;
early growth response 3;
distal-less homeo box 5;
hypothetical protein FLJ20373;
aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II);
biglycan;
transcriptional co-activator with PDZ-binding motif (TAZ);
fibronectin 1;
proenkephalin;
integrin, beta-like 1 (with EGF-like repeat domains);
Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1968422;
EphA3;
KIAA0367 protein;
natriuretic peptide receptor C/guanylate cyclase C (atrionatriuretic peptide receptor C);
hypothetical protein FLJ14054;
Homo sapiens mRNA;
cDNA DKFZp564B222 (from clone DKFZp564B222);
BCL2/adenovirus E1B 19 kDa interacting protein 3-like;
AE binding protein 1;
cytochrome c oxidase subunit VIIa polypeptide 1 (muscle);
similar to neuralin 1;
B cell translocation gene 1;
hypothetical protein FLJ23191; and
DKFZp586L151;
h) 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; and
i) lack of secretion of at least one of TGF-beta2, ANG2, PDGFbb, MIP1b, 1309, MDC, and VEGF, as detected by ELISA.
8 Assignments
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Accused Products
Abstract
Cells derived from postpartum tissue such as the umbilical cord and placenta, and methods for their use to regenerate, repair, and improve neural tissue, and to improve behavior and neurological function in stroke patients are disclosed.
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Citations
41 Claims
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1. A method of treating a patient having an acute neurodegenerative condition, the method comprising administering to the patient postpartum-derived cells in an amount effective to treat the neurodegenerative condition, wherein the postpartum-derived cells are derived from human placental or umbilical cord tissue substantially free of blood, wherein the cells are capable of self-renewal and expansion in culture and have the potential to differentiate into cells of at least a neural phenotype;
- wherein the cells require L-valine for growth and can grow in at least about 5% oxygen;
wherein the cells further comprise at least one of the following characteristics;
a) potential for at least about 40 doublings in culture;
b) attachment and expansion on a coated or uncoated tissue culture vessel, wherein the coated tissue culture vessel comprises a coating of gelatin, laminin, collagen, polyomithine, vitronectin, or fibronectin;
c) production of at least one of tissue factor, vimentin, and alpha-smooth muscle actin;
d) production of at least one of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A, B, C;
e) 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;
f) expression of a gene, 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 a gene encoding;
interleukin 8;
reticulon 1;
chemokine (C-X-C motif) ligand 1 (melonoma growth stimulating activity, alpha);
chemokine (C-X-C motif) ligand 6 (granulocyte chemotactic protein
2);
chemokine (C-X-C motif) ligand 3;
tumor necrosis factor, alpha-induced protein 3;
C-type lectin superfamily member 2;
Wilms tumor 1;
aldehyde dehydrogenase 1 family member A2;
renin;
oxidized low density lipoprotein receptor 1;
Homo sapiens clone IMAGE;
4179671;
protein kinase C zeta;
hypothetical protein DKFZp564F013;
downregulated in ovarian cancer 1; and
Homo sapiens gene from clone DKFZp547k1113.g) expression of a gene, 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 a gene encoding;
short stature homeobox 2;
heat shock 27 kDa protein 2;
chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor
1);
elastin (supravalvular aortic stenosis, Williams-Beuren syndrome);
Homo sapiens mRNA;
cDNA DKFZp586M2022 (from clone DKFZp586M2022);
mesenchyme homeo box 2 (growth arrest-specific homeo box);
sine oculis homeobox homolog 1 (Drosophila);
crystallin, alpha B;
disheveled associated activator of morphogenesis 2;
DKFZP586B2420 protein;
similar to neuralin 1;
tetranectin (plasminogen binding protein);
src homology three (SH3) and cysteine rich domain;
cholesterol 25-hydroxylase;
runt-related transcription factor 3;
interleukin 11 receptor, alpha;
procollagen C-endopeptidase enhancer;
frizzled homolog 7 (Drosophila);
hypothetical gene BC008967;
collagen, type VIII, alpha 1;
tenascin C (hexabrachion);
iroquois homeobox protein 5;
hephaestin;
integrin, beta 8;
synaptic vesicle glycoprotein 2;
neuroblastoma, suppression of tumorigenicity 1;
insulin-like growth factor binding protein 2, 36 kDa;
Homo sapiens cDNA FLJ12280 fis, clone MAMMA1001744;
cytokine receptor-like factor 1;
potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4;
integrin, beta 7;
transcriptional co-activator with PDZ-binding motif (TAZ);
sine oculis homeobox homolog 2 (Drosophila);
KIAA1034 protein;
vesicle-associated membrane protein 5 (myobrevin);
EGF-containing fibulin-like extracellular matrix protein 1;
early growth response 3;
distal-less homeo box 5;
hypothetical protein FLJ20373;
aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II);
biglycan;
transcriptional co-activator with PDZ-binding motif (TAZ);
fibronectin 1;
proenkephalin;
integrin, beta-like 1 (with EGF-like repeat domains);
Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1968422;
EphA3;
KIAA0367 protein;
natriuretic peptide receptor C/guanylate cyclase C (atrionatriuretic peptide receptor C);
hypothetical protein FLJ14054;
Homo sapiens mRNA;
cDNA DKFZp564B222 (from clone DKFZp564B222);
BCL2/adenovirus E1B 19 kDa interacting protein 3-like;
AE binding protein 1;
cytochrome c oxidase subunit VIIa polypeptide 1 (muscle);
similar to neuralin 1;
B cell translocation gene 1;
hypothetical protein FLJ23191; and
DKFZp586L151;
h) 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; and
i) lack of secretion of at least one of TGF-beta2, ANG2, PDGFbb, MIP1b, 1309, MDC, and VEGF, as detected by ELISA. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 28, 29)
- wherein the cells require L-valine for growth and can grow in at least about 5% oxygen;
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16. A pharmaceutical composition for treating a patient having an acute neurodegenerative condition, comprising a pharmaceutically acceptable carrier and postpartum-derived cells in an effective to treat the neurodegenerative condition wherein the postpartum-derived cells are derived from human placental or umbilical cord tissue substantially free of blood, wherein the cells are capable of self-renewal and expansion in culture and have the potential to differentiate into cells of at least a neural phenotype;
- wherein the cells require L-valine for growth and can grow in at least about 5% oxygen;
wherein the cells further comprise at least one of the following characteristics;
a) potential for at least about 40 doublings in culture;
b) attachment and expansion on a coated or uncoated tissue culture vessel, wherein the coated tissue culture vessel comprises a coating of gelatin, laminin, collagen, polyomithine, vitronectin, or fibronectin;
c) production of at least one of tissue factor, vimentin, and alpha-smooth muscle actin;
d) production of at least one of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A, B, C;
e) 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;
f) expression of a gene, 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 a gene encoding;
interleukin 8;
reticulon 1;
chemokine (C-X-C motif) ligand 1 (melonoma growth stimulating activity, alpha);
chemokine (C-X-C motif) ligand 6 (granulocyte chemotactic protein
2);
chemokine (C-X-C motif) ligand 3;
tumor necrosis factor, alpha-induced protein 3;
C-type lectin superfamily member 2;
Wilms tumor 1;
aldehyde dehydrogenase 1 family member A2;
renin;
oxidized low density lipoprotein receptor 1;
Homo sapiens clone IMAGE;
4179671;
protein kinase C zeta;
hypothetical protein DKFZp564F013;
downregulated in ovarian cancer 1; and
Homo sapiens gene from clone DKFZp547k1113.g) expression of a gene, 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 a gene encoding;
short stature homeobox 2;
heat shock 27 kDa protein 2;
chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor
1);
elastin (supravalvular aortic stenosis, Williams-Beuren syndrome);
Homo sapiens mRNA;
cDNA DKFZp586M2022 (from clone DKFZp586M2022);
mesenchyme homeo box 2 (growth arrest-specific homeo box);
sine oculis homeobox homolog 1 (Drosophila);
crystallin, alpha B;
disheveled associated activator of morphogenesis 2;
DKFZP586B2420 protein;
similar to neuralin 1;
tetranectin (plasminogen binding protein);
src homology three (SH3) and cysteine rich domain;
cholesterol 25-hydroxylase;
runt-related transcription factor 3;
interleukin 11 receptor, alpha;
procollagen C-endopeptidase enhancer;
frizzled homolog 7 (Drosophila);
hypothetical gene BC008967;
collagen, type VIII, alpha 1;
tenascin C (hexabrachion);
iroquois homeobox protein 5;
hephaestin;
integrin, beta 8;
synaptic vesicle glycoprotein 2;
neuroblastoma, suppression of tumorigenicity 1;
insulin-like growth factor binding protein 2, 36 kDa;
Homo sapiens cDNA FLJ12280 fis, clone MAMMA1001744;
cytokine receptor-like factor 1;
potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4;
integrin, beta 7;
transcriptional co-activator with PDZ-binding motif (TAZ);
sine oculis homeobox homolog 2 (Drosophila);
KIAA1034 protein;
vesicle-associated membrane protein 5 (myobrevin);
EGF-containing fibulin-like extracellular matrix protein 1;
early growth response 3;
distal-less homeo box 5;
hypothetical protein FLJ20373;
aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II);
biglycan;
transcriptional co-activator with PDZ-binding motif (TAZ);
fibronectin 1;
proenkephalin;
integrin, beta-like 1 (with EGF-like repeat domains);
Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1968422;
EphA3;
KIAA0367 protein;
natriuretic peptide receptor C/guanylate cyclase C (atrionatriuretic peptide receptor C);
hypothetical protein FLJ14054;
Homo sapiens mRNA;
cDNA DKFZp564B222 (from clone DKFZp564B222);
BCL2/adenovirus E1B 19 kDa interacting protein 3-like;
AE binding protein 1;
cytochrome c oxidase subunit VIIa polypeptide 1 (muscle);
similar to neuralin 1;
B cell translocation gene 1;
hypothetical protein FLJ23191; and
DKFZp586L151;
h) 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; and
i) lack of secretion of at least one of TGF-beta2, ANG2, PDGFbb, MIP1b, 1309, MDC, and VEGF, as detected by ELISA. - View Dependent Claims (17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)
- wherein the cells require L-valine for growth and can grow in at least about 5% oxygen;
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30. A method of treating stroke in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a cell preparation wherein the cell preparation comprises isolated postpartum-derived cell comprising a cell derived from human placental or umbilical cord tissue substantially free of blood, wherein the cell is capable of self-renewal and expansion in culture and has the potential to differentiate into a cell of a neural phenotype;
- wherein the cell requires L-valine for growth and is capable of growth in at least about 5% oxygen;
wherein the cell further comprises at least one of the following characteristics;
a) potential for at least about 40 doublings in culture;
b) attachment and expansion on a coated or uncoated tissue culture vessel, wherein the coated tissue culture vessel comprises a coating of gelatin, laminin, collagen, polyornithine, vitronectin, or fibronectin;
c) production of at least one of tissue factor, vimentin, and alpha-smooth muscle actin;
d) production of at least one of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A, B, C;
e) 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;
f) expression of a gene, 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 a gene encoding;
interleukin 8;
reticulon 1;
chemokine (C-X-C motif) ligand 1 (melonoma growth stimulating activity, alpha);
chemokine (C-X-C motif) ligand 6 (granulocyte chemotactic protein
2);
chemokine (C-X-C motif) ligand 3;
tumor necrosis factor, alpha-induced protein 3;
C-type lectin superfamily member 2;
Wilms tumor 1;
aldehyde dehydrogenase 1 family member A2;
renin;
oxidized low density lipoprotein receptor 1;
Homo sapiens clone IMAGE;
4179671;
protein kinase C zeta;
hypothetical protein DKFZp564F013;
downregulated in ovarian cancer 1; and
Homo sapiens gene from clone DKFZp547k1113.g) expression of a gene, 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 a gene encoding;
short stature homeobox 2;
heat shock 27 kDa protein 2;
chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor
1);
elastin (supravalvular aortic stenosis, Williams-Beuren syndrome);
Homo sapiens mRNA;
cDNA DKFZp586M2022 (from clone DKFZp586M2022);
mesenchyme homeo box 2 (growth arrest-specific homeo box);
sine oculis homeobox homolog 1 (Drosophila);
crystallin, alpha B;
disheveled associated activator of morphogenesis 2;
DKFZP586B2420 protein;
similar to neuralin 1;
tetranectin (plasminogen binding protein);
src homology three (SH3) and cysteine rich domain;
cholesterol 25-hydroxylase;
runt-related transcription factor 3;
interleukin 11 receptor, alpha;
procollagen C-endopeptidase enhancer;
frizzled homolog 7 (Drosophila);
hypothetical gene BC008967;
collagen, type VIII, alpha 1;
tenascin C (hexabrachion);
iroquois homeobox protein 5;
hephaestin;
integrin, beta 8;
synaptic vesicle glycoprotein 2;
neuroblastoma, suppression of tumorigenicity 1;
insulin-like growth factor binding protein 2, 36 kDa;
Homo sapiens cDNA FLJ12280 fis, clone MAMMA1001744;
cytokine receptor-like factor 1;
potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4;
integrin, beta 7;
transcriptional co-activator with PDZ-binding motif (TAZ);
sine oculis homeobox homolog 2 (Drosophila);
KIAA1034 protein;
vesicle-associated membrane protein 5 (myobrevin);
EGF-containing fibulin-like extracellular matrix protein 1;
early growth response 3;
distal-less homeo box 5;
hypothetical protein FLJ20373;
aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II);
biglycan;
transcriptional co-activator with PDZ-binding motif (TAZ);
fibronectin 1;
proenkephalin;
integrin, beta-like 1 (with EGF-like repeat domains);
Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1968422;
EphA3;
KIAA0367 protein;
natriuretic peptide receptor C/guanylate cyclase C (atrionatriuretic peptide receptor C);
hypothetical protein FLJ14054;
Homo sapiens mRNA;
cDNA DKFZp564B222 (from clone DKFZp564B222);
BCL2/adenovirus E1B 19 kDa interacting protein 3-like;
AE binding protein 1;
cytochrome c oxidase subunit VIIa polypeptide 1 (muscle);
similar to neuralin 1;
B cell translocation gene 1;
hypothetical protein FLJ23191; and
DKFZp586L151;
h) 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; and
i) lack of secretion of at least one of TGF-beta2, ANG2, PDGFbb, MIP1b, 1309, MDC, and VEGF, as detected by ELISA. - View Dependent Claims (31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41)
- wherein the cell requires L-valine for growth and is capable of growth in at least about 5% oxygen;
Specification