Repair and regeneration of ocular tissue using postpartum-derived cells

Abstract

Cells derived from postpartum umbilicus and placenta are disclosed. Pharmaceutical compositions, devices and methods for the regeneration or repair of ocular tissue using the postpartum-derived cells are also disclosed.

1 . An 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, 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 MAMMAI001744; 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.    
     
     
         2 . The postpartum-derived cell of  claim 1  isolated in the presence of one or more enzyme activities comprising metalloprotease activity, mucolytic activity and neutral protease activity.  
     
     
         3 . The postpartum-derived cell of  claim 6  comprising a normal karyotype.  
     
     
         4 . The postpartum-derived cell of  claim 9  wherein the cell comprises each of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, and HLA-A,B,C and does not comprise any of CD31, CD34, CD45, CD117, CD141, or HLA-DR,DP,DQ, as detected by flow cytometry.  
     
     
         5 . A cell population comprising the postpartum-derived cell of  claim 1 .  
     
     
         6 . The cell population of  claim 5 , which is a substantially homogeneous population of the postpartum-derived cells.  
     
     
         7 . The cell population of  claim 6  comprising a clonal cell line of postpartum-derived cells.  
     
     
         8 . The cell population of  claim 5 , which is a heterogeneous population comprising the postpartum-derived cells and at least one other cell type.  
     
     
         9 . The cell population of  claim 8 , wherein the at least one other cell type is an astrocyte, oligodendrocyte, neuron, neural progenitor, neural stem cell, retinal epithelial stem cell, corneal epithelial stem cell or other multipotent or pluripotent stem cell.  
     
     
         10 . A cell lysate prepared from the cell population of  claim 5 .  
     
     
         11 . A soluble cell fraction prepared from the cell lysate of  claim 10 .  
     
     
         12 . An extracellular matrix prepared from the cell population of  claim 5 .  
     
     
         13 . The cell population of  claim 5 , cultured in contact with one or more factors that stimulate stem cell differentiation toward a neural or epithelial lineage.  
     
     
         14 - 29 . (canceled)  
     
     
         30 . A pharmaceutical composition for treating a patient having an ocular degenerative condition, comprising a pharmaceutically acceptable carrier and multipotent or pluripotent cells isolated from a postpartum placenta or umbilical cord in an amount effective to treat the ocular degenerative condition.  
     
     
         31 . The pharmaceutical composition of  claim 30 , wherein the ocular degenerative condition is an acute ocular degenerative condition.  
     
     
         32 . The pharmaceutical composition of  claim 30 , wherein the ocular degenerative condition is a chronic or progressive degenerative condition.  
     
     
         33 . The pharmaceutical composition of  claim 30 , wherein the multipotent or pluripotent cells are isolated postpartum-derived cells 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, 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.    
     
     
         34 . The pharmaceutical composition of  claim 30 , wherein the cells are induced in vitro to differentiate into a neural or epithelial lineage cells prior to formulation of the composition.  
     
     
         35 . The pharmaceutical composition of  claim 30 , comprising at least one other cell type.  
     
     
         36 . The pharmaceutical composition of  claim 35 , wherein the other cell type is an astrocyte, oligodendrocyte, neuron, neural progenitor, neural stem cell, retinal epithelial stem cell, corneal epithelial stem cell, or other multipotent or pluripotent stem cell.  
     
     
         37 . The pharmaceutical composition of  claim 30 , comprising at least one other agent.  
     
     
         38 . The pharmaceutical composition of  claim 37 , wherein the other agent is a drug for treating the ocular degenerative disorder.  
     
     
         39 . The pharmaceutical composition of  claim 30 , formulated for administration to the surface of an eye.  
     
     
         40 . The pharmaceutical composition of  claim 30 , formulated for administration to the interior of an eye.  
     
     
         41 . The pharmaceutical composition of  claim 30 , formulated as a matrix or scaffold containing the cells.  
     
     
         42 . A kit for treating a patient having an ocular degenerative condition, the kit comprising a pharmaceutically acceptable carrier, a population of multipotent or pluripotent cells isolated from postpartum placenta or umbilicus, and instructions for using the kit in a method of treating the patient.  
     
     
         43 . The kit of  claim 42 , which further comprises at least one reagent and instructions for culturing the cells.  
     
     
         44 . The kit of  claim 42 , which further comprises a population of at least one other cell type.  
     
     
         45 . The kit of  claim 42 , which further comprises at least one other agent for treating an ocular degenerative condition.  
     
     
         46 . (canceled)  
     
     
         47 . A pharmaceutical composition for treating a patient having an ocular degenerative condition, which comprises a pharmaceutically acceptable carrier and a preparation made from multipotent or pluripotent cells isolated from a postpartum placenta or umbilical cord, in an amount effective to treat the ocular degenerative condition, wherein the preparation comprises a cell lysate of the cells, or a conditioned medium in which the cells were grown or an extracellular matrix of the cells.  
     
     
         48 . A kit for treating a patient having an ocular degenerative condition, which comprises a pharmaceutically acceptable carrier, a preparation made from multipotent or pluripotent cells isolated from a postpartum placenta or umbilical cord, wherein the preparation comprises a cell lysate of the cells, or a conditioned medium in which the cells were grown or an extracellular matrix of the cells, and instructions for using the kit components for treatment of the ocular degenerative condition.  
     
     
         49 . (canceled)  
     
     
         50 . A kit for increasing the survival, growth or activity of cells for transplantation to treat an ocular degenerative disorder, comprising cultured cells derived from postpartum placental or umbilical tissue and instructions for co-culturing the cells for transplantation with the postpartum cells under conditions effective to increase the survival, growth or activity of the cells for transplantation.  
     
     
         51 . The pharmaceutical composition of  claim 47 , wherein the ocular degenerative condition is an acute ocular degenerative condition.  
     
     
         52 . The pharmaceutical composition of  claim 47 , wherein the ocular degenerative condition is a chronic or progressive degenerative condition.  
     
     
         53 . The pharmaceutical composition of  claim 47 , wherein the multipotent or pluripotent cells are isolated postpartum-derived cells 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.    
     
     
         54 . The pharmaceutical composition of  claim 47 , wherein the cells are induced in vitro to differentiate into a neural or epithelial lineage cells prior to making the preparation.  
     
     
         55 . The pharmaceutical composition of  claim 47 , comprising at least one other agent.  
     
     
         56 . The pharmaceutical composition of  claim 55 , wherein the other agent is a drug for treating the ocular degenerative disorder.  
     
     
         57 . The pharmaceutical composition of  claim 47 , formulated for administration to the surface of an eye.  
     
     
         58 . The pharmaceutical composition of  claim 47 , formulated for administration to the interior of an eye.  
     
     
         59 . The pharmaceutical composition of  claim 47 , formulated as a matrix or scaffold containing the preparation.  
     
     
         60 . The kit of  claim 48 , which further comprises at least one other agent for treating an ocular degenerative condition.  
     
     
         61 . The kit of  claim 50 , which further comprises at least one reagent and instructions for culturing the cells.  
     
     
         62 . The kit of  claim 50 , which further comprises a population of at least one other cell type.  
     
     
         63 . The kit of  claim 50 , which further comprises at least one other agent for treating an ocular degenerative condition.