COMPOSITIONS AND METHODS FOR INHIBITING ADVERSE IMMUNE RESPONSE IN HISTOCOMPATIBILITY-MISMATCHED TRANSPLANTATION
First Claim
1. A method for inhibiting an adverse immune response in a transplant recipient that is histocompatibility-mismatched to the transplant donor, comprising administering a cell composition to the transplant recipient in an amount effective for inhibiting the adverse immune response, wherein the cell composition comprises a pharmaceutically acceptable carrier and postpartum-derived cells derived from human postpartum tissue substantially free of blood, said cells being capable of self-renewal and expansion in culture, wherein the cells require L-Valine for growth and are capable of growth in an atmosphere containing oxygen from about 5% to at least about 20%, and wherein the cells 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 a 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 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;
g) expression of at least one of C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 2 (activation-induced);
Wilms tumor 1;
aldehyde dehydrogenase 1 family, member A2; and
renin;
oxidized low density lipoprotein (lectin-like) receptor 1;
Homo sapiens, clone IMAGE;
4179671, mRNA, partial cds;
protein kinase C, zeta;
hypothetical protein DKFZp564F013;
downregulated in ovarian cancer 1;
Homo sapiens mRNA; and
cDNA DKFZp547K1113 (from clone DKFZp547K1113);
h) 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;
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 homeobox 2 (growth arrest-specific homeobox);
sine oculis homeobox homolog 1 (Drosophila);
crystallin, alpha B;
dishevelled associated activator of morphogenesis 2;
DKFZP586B2420 protein;
similar to neuralin 1;
tetranectin (plasminogen binding protein);
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 (Drosophila);
hypothetical gene BC008967;
collagen, type VIII, alpha 1;
tenascin C (hexabrachion);
iroquois homeobox protein 5;
hephaestin;
integrin, beta 8;
synaptic vesicle glycoprotein 2;
Homo sapiens 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 (Drosophila);
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);
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);
vesicle-associated membrane protein 5 (myobrevin);
EGF-containing fibulin-like extracellular matrix protein 1;
BCL2/adenovirus EIB 19 kDa interacting protein 3-like;
AE binding protein 1;
cytochrome c oxidase subunit VIIa polypeptide 1 (muscle);
neuroblastoma, suppression of tumorigenicity 1;
insulin-like growth factor binding protein 2, 36 kDa;
i) 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
j) lack of secretion of at least one of TGF-beta2, ANG2, PDGFbb, MIP1b, 1309, MDC, and VEGF, as detected by ELISA.
8 Assignments
0 Petitions
Accused Products
Abstract
Cell-based compositions and methods of their use to inhibit an adverse immune response such as graft versus host disease or rejection of transplanted tissue in a transplant recipient that is histocompatibility mismatched to the transplant donor are disclosed. The compositions and methods utilize postpartum-derived cells, such as cells derived from the placenta or umbilicus.
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Citations
47 Claims
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1. A method for inhibiting an adverse immune response in a transplant recipient that is histocompatibility-mismatched to the transplant donor, comprising administering a cell composition to the transplant recipient in an amount effective for inhibiting the adverse immune response, wherein the cell composition comprises a pharmaceutically acceptable carrier and postpartum-derived cells derived from human postpartum tissue substantially free of blood, said cells being capable of self-renewal and expansion in culture, wherein the cells require L-Valine for growth and are capable of growth in an atmosphere containing oxygen from about 5% to at least about 20%, and wherein the cells 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 a 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 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;
g) expression of at least one of C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 2 (activation-induced);
Wilms tumor 1;
aldehyde dehydrogenase 1 family, member A2; and
renin;
oxidized low density lipoprotein (lectin-like) receptor 1;
Homo sapiens, clone IMAGE;
4179671, mRNA, partial cds;
protein kinase C, zeta;
hypothetical protein DKFZp564F013;
downregulated in ovarian cancer 1;
Homo sapiens mRNA; and
cDNA DKFZp547K1113 (from clone DKFZp547K1113);
h) 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;
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 homeobox 2 (growth arrest-specific homeobox);
sine oculis homeobox homolog 1 (Drosophila);
crystallin, alpha B;
dishevelled associated activator of morphogenesis 2;
DKFZP586B2420 protein;
similar to neuralin 1;
tetranectin (plasminogen binding protein);
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 (Drosophila);
hypothetical gene BC008967;
collagen, type VIII, alpha 1;
tenascin C (hexabrachion);
iroquois homeobox protein 5;
hephaestin;
integrin, beta 8;
synaptic vesicle glycoprotein 2;
Homo sapiens 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 (Drosophila);
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);
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);
vesicle-associated membrane protein 5 (myobrevin);
EGF-containing fibulin-like extracellular matrix protein 1;
BCL2/adenovirus EIB 19 kDa interacting protein 3-like;
AE binding protein 1;
cytochrome c oxidase subunit VIIa polypeptide 1 (muscle);
neuroblastoma, suppression of tumorigenicity 1;
insulin-like growth factor binding protein 2, 36 kDa;
i) 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
j) 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, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28)
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29. A method for inhibiting an adverse immune response in a transplant recipient that is histocompatibility-mismatched to the transplant donor comprising administering to the patient a composition comprising one or more of a conditioned medium generated by postpartum-derived cells, a cell lysate generated from postpartum-derived cells, a soluble cell fraction generated from postpartum-derived cells, or an extracellular matrix containing postpartum-derived cells, wherein the postpartum-derived cells are derived from human postpartum tissue substantially free of blood and capable of self-renewal and expansion in culture, wherein the cells require L-Valine for growth and are capable of growth in an atmosphere containing oxygen from about 5% to at least about 20%, and wherein the cells 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 a 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 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;
g) expression of at least one of C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 2 (activation-induced);
Wilms tumor 1;
aldehyde dehydrogenase 1 family, member A2; and
renin;
oxidized low density lipoprotein (lectin-like) receptor 1;
Homo sapiens, clone IMAGE;
4179671, mRNA, partial cds;
protein kinase C, zeta;
hypothetical protein DKFZp564F013;
downregulated in ovarian cancer 1;
Homo sapiens mRNA; and
cDNA DKFZp547K1113 (from clone DKFZp547K1113);
h) 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;
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 homeobox 2 (growth arrest-specific homeobox);
sine oculis homeobox homolog 1 (Drosophila);
crystallin, alpha B;
dishevelled associated activator of morphogenesis 2;
DKFZP586B2420 protein;
similar to neuralin 1;
tetranectin (plasminogen binding protein);
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 (Drosophila);
hypothetical gene BC008967;
collagen, type VIII, alpha 1;
tenascin C (hexabrachion);
iroquois homeobox protein 5;
hephaestin;
integrin, beta 8;
synaptic vesicle glycoprotein 2;
Homo sapiens 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 (Drosophila);
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);
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);
vesicle-associated membrane protein 5 (myobrevin);
EGF-containing fibulin-like extracellular matrix protein 1;
BCL2/adenovirus EIB 19 kDa interacting protein 3-like;
AE binding protein 1;
cytochrome c oxidase subunit VIIa polypeptide 1 (muscle);
neuroblastoma, suppression of tumorigenicity 1;
insulin-like growth factor binding protein 2, 36 kDa;
i) 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
j) lack of secretion of at least one of TGF-beta2, ANG2, PDGFbb, MIP1b, 1309, MDC, and VEGF, as detected by ELISA. - View Dependent Claims (30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47)
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Specification