ES2554492T3 - Microvesículas (MVs) derivadas de citoblastos de etapa adulta para uso en el tratamiento terapéutico de una enfermedad neoplásica. - Google Patents
Microvesículas (MVs) derivadas de citoblastos de etapa adulta para uso en el tratamiento terapéutico de una enfermedad neoplásica. Download PDFInfo
- Publication number
- ES2554492T3 ES2554492T3 ES11705585.5T ES11705585T ES2554492T3 ES 2554492 T3 ES2554492 T3 ES 2554492T3 ES 11705585 T ES11705585 T ES 11705585T ES 2554492 T3 ES2554492 T3 ES 2554492T3
- Authority
- ES
- Spain
- Prior art keywords
- cells
- mvs
- tumor
- derived
- cytoblast
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 38
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 12
- 201000010099 disease Diseases 0.000 title claims abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 11
- 230000001613 neoplastic effect Effects 0.000 title claims abstract description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 71
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 28
- 210000004185 liver Anatomy 0.000 claims description 15
- 229960004679 doxorubicin Drugs 0.000 claims description 14
- 229960004528 vincristine Drugs 0.000 claims description 9
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 9
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 9
- 230000037396 body weight Effects 0.000 claims description 8
- 206010006187 Breast cancer Diseases 0.000 claims description 7
- -1 Sunitini b Chemical compound 0.000 claims description 7
- 210000001185 bone marrow Anatomy 0.000 claims description 6
- 239000000824 cytostatic agent Substances 0.000 claims description 5
- 239000002254 cytotoxic agent Substances 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 231100000433 cytotoxic Toxicity 0.000 claims description 4
- 230000001472 cytotoxic effect Effects 0.000 claims description 4
- 229960003957 dexamethasone Drugs 0.000 claims description 4
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 4
- 229960000688 pomalidomide Drugs 0.000 claims description 4
- UVSMNLNDYGZFPF-UHFFFAOYSA-N pomalidomide Chemical compound O=C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O UVSMNLNDYGZFPF-UHFFFAOYSA-N 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 3
- 229960004942 lenalidomide Drugs 0.000 claims description 3
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 claims description 3
- 208000014018 liver neoplasm Diseases 0.000 claims description 3
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 190000008236 Carboplatin Chemical compound 0.000 claims description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 2
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 2
- 206010061968 Gastric neoplasm Diseases 0.000 claims description 2
- 206010019695 Hepatic neoplasm Diseases 0.000 claims description 2
- 239000002136 L01XE07 - Lapatinib Substances 0.000 claims description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 2
- 229960004562 carboplatin Drugs 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 229960004397 cyclophosphamide Drugs 0.000 claims description 2
- 229960003668 docetaxel Drugs 0.000 claims description 2
- 229960001904 epirubicin Drugs 0.000 claims description 2
- 229960004891 lapatinib Drugs 0.000 claims description 2
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 2
- 229960001756 oxaliplatin Drugs 0.000 claims description 2
- 208000023958 prostate neoplasm Diseases 0.000 claims description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 2
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 2
- 229960002930 sirolimus Drugs 0.000 claims description 2
- 238000007910 systemic administration Methods 0.000 claims description 2
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 claims description 2
- 229960002066 vinorelbine Drugs 0.000 claims description 2
- 208000037841 lung tumor Diseases 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 157
- 230000006907 apoptotic process Effects 0.000 description 36
- 102000006382 Ribonucleases Human genes 0.000 description 35
- 108010083644 Ribonucleases Proteins 0.000 description 35
- 230000035755 proliferation Effects 0.000 description 32
- 238000011534 incubation Methods 0.000 description 24
- 238000002474 experimental method Methods 0.000 description 23
- 230000000694 effects Effects 0.000 description 22
- 238000000338 in vitro Methods 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 238000002347 injection Methods 0.000 description 18
- 239000007924 injection Substances 0.000 description 18
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 16
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 15
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 14
- 239000002609 medium Substances 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 13
- 238000001727 in vivo Methods 0.000 description 13
- 239000012091 fetal bovine serum Substances 0.000 description 12
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 11
- 238000011579 SCID mouse model Methods 0.000 description 11
- 230000003511 endothelial effect Effects 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 230000000118 anti-neoplastic effect Effects 0.000 description 10
- 201000011510 cancer Diseases 0.000 description 10
- 238000010186 staining Methods 0.000 description 10
- 230000004614 tumor growth Effects 0.000 description 10
- 230000001640 apoptogenic effect Effects 0.000 description 9
- 238000002955 isolation Methods 0.000 description 9
- 108010082117 matrigel Proteins 0.000 description 9
- 239000006228 supernatant Substances 0.000 description 9
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 8
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 8
- 229930182555 Penicillin Natural products 0.000 description 8
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 8
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 8
- 229940049954 penicillin Drugs 0.000 description 8
- 229960005322 streptomycin Drugs 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 238000010599 BrdU assay Methods 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- 229930040373 Paraformaldehyde Natural products 0.000 description 6
- 210000002889 endothelial cell Anatomy 0.000 description 6
- 229920002866 paraformaldehyde Polymers 0.000 description 6
- 210000000130 stem cell Anatomy 0.000 description 6
- 238000005199 ultracentrifugation Methods 0.000 description 6
- 208000007766 Kaposi sarcoma Diseases 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 201000008274 breast adenocarcinoma Diseases 0.000 description 5
- 238000010348 incorporation Methods 0.000 description 5
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 5
- 239000013049 sediment Substances 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- 102100032912 CD44 antigen Human genes 0.000 description 4
- 108050006400 Cyclin Proteins 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 230000035519 G0 Phase Effects 0.000 description 4
- 230000010190 G1 phase Effects 0.000 description 4
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 101710163270 Nuclease Proteins 0.000 description 4
- 102000009339 Proliferating Cell Nuclear Antigen Human genes 0.000 description 4
- 230000033115 angiogenesis Effects 0.000 description 4
- 238000003782 apoptosis assay Methods 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 239000003593 chromogenic compound Substances 0.000 description 4
- 239000002577 cryoprotective agent Substances 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 238000002635 electroconvulsive therapy Methods 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 4
- 238000010166 immunofluorescence Methods 0.000 description 4
- 239000007943 implant Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000001000 micrograph Methods 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 239000012188 paraffin wax Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000012679 serum free medium Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 102100022464 5'-nucleotidase Human genes 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 238000009010 Bradford assay Methods 0.000 description 3
- 102100023126 Cell surface glycoprotein MUC18 Human genes 0.000 description 3
- 102100037241 Endoglin Human genes 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 3
- 101000678236 Homo sapiens 5'-nucleotidase Proteins 0.000 description 3
- 101000623903 Homo sapiens Cell surface glycoprotein MUC18 Proteins 0.000 description 3
- 101000881679 Homo sapiens Endoglin Proteins 0.000 description 3
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 3
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000012288 TUNEL assay Methods 0.000 description 3
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 3
- 238000000540 analysis of variance Methods 0.000 description 3
- 239000007640 basal medium Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 238000001516 cell proliferation assay Methods 0.000 description 3
- 108091092356 cellular DNA Proteins 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 230000000877 morphologic effect Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 102000013415 peroxidase activity proteins Human genes 0.000 description 3
- 108040007629 peroxidase activity proteins Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000003161 ribonuclease inhibitor Substances 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 230000017423 tissue regeneration Effects 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 230000005740 tumor formation Effects 0.000 description 3
- 210000003606 umbilical vein Anatomy 0.000 description 3
- 102100024210 CD166 antigen Human genes 0.000 description 2
- 101150013553 CD40 gene Proteins 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 229930182566 Gentamicin Natural products 0.000 description 2
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 2
- 101000980840 Homo sapiens CD166 antigen Proteins 0.000 description 2
- 101000935043 Homo sapiens Integrin beta-1 Proteins 0.000 description 2
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- 102100025304 Integrin beta-1 Human genes 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 241000239218 Limulus Species 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 108010004729 Phycoerythrin Proteins 0.000 description 2
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 2
- 102000004357 Transferases Human genes 0.000 description 2
- 108090000992 Transferases Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 230000009816 chondrogenic differentiation Effects 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 230000008472 epithelial growth Effects 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 229960002518 gentamicin Drugs 0.000 description 2
- 230000001434 glomerular Effects 0.000 description 2
- 230000003394 haemopoietic effect Effects 0.000 description 2
- 229960000890 hydrocortisone Drugs 0.000 description 2
- 238000002650 immunosuppressive therapy Methods 0.000 description 2
- 230000006882 induction of apoptosis Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 238000012758 nuclear staining Methods 0.000 description 2
- 230000009818 osteogenic differentiation Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- INAAIJLSXJJHOZ-UHFFFAOYSA-N pibenzimol Chemical compound C1CN(C)CCN1C1=CC=C(N=C(N2)C=3C=C4NC(=NC4=CC=3)C=3C=CC(O)=CC=3)C2=C1 INAAIJLSXJJHOZ-UHFFFAOYSA-N 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 206010040882 skin lesion Diseases 0.000 description 2
- 231100000444 skin lesion Toxicity 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 108010047303 von Willebrand Factor Proteins 0.000 description 2
- 102100036537 von Willebrand factor Human genes 0.000 description 2
- 229960001134 von willebrand factor Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 206010003594 Ataxia telangiectasia Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- 108010025714 CD146 Antigen Proteins 0.000 description 1
- 102000049932 CD146 Antigen Human genes 0.000 description 1
- 239000005461 Canertinib Substances 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- AHCYMLUZIRLXAA-SHYZEUOFSA-N Deoxyuridine 5'-triphosphate Chemical group O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 AHCYMLUZIRLXAA-SHYZEUOFSA-N 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 108010036395 Endoglin Proteins 0.000 description 1
- 102000012085 Endoglin Human genes 0.000 description 1
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010003471 Fetal Proteins Proteins 0.000 description 1
- 102000004641 Fetal Proteins Human genes 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 230000010337 G2 phase Effects 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 101000998011 Homo sapiens Keratin, type I cytoskeletal 19 Proteins 0.000 description 1
- 101001008874 Homo sapiens Mast/stem cell growth factor receptor Kit Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100033420 Keratin, type I cytoskeletal 19 Human genes 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 101150014058 MMP1 gene Proteins 0.000 description 1
- 102100027754 Mast/stem cell growth factor receptor Kit Human genes 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 101100518992 Mus musculus Pax2 gene Proteins 0.000 description 1
- 229920002274 Nalgene Polymers 0.000 description 1
- 102000008730 Nestin Human genes 0.000 description 1
- 108010088225 Nestin Proteins 0.000 description 1
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 1
- 102100035593 POU domain, class 2, transcription factor 1 Human genes 0.000 description 1
- 101710084414 POU domain, class 2, transcription factor 1 Proteins 0.000 description 1
- 102100035423 POU domain, class 5, transcription factor 1 Human genes 0.000 description 1
- 101710126211 POU domain, class 5, transcription factor 1 Proteins 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 230000018199 S phase Effects 0.000 description 1
- 102100038081 Signal transducer CD24 Human genes 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
- 102000013127 Vimentin Human genes 0.000 description 1
- 108010065472 Vimentin Proteins 0.000 description 1
- CDXSJGDDABYYJV-UHFFFAOYSA-N acetic acid;ethanol Chemical compound CCO.CC(O)=O CDXSJGDDABYYJV-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000009815 adipogenic differentiation Effects 0.000 description 1
- 230000002293 adipogenic effect Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- RGCKGOZRHPZPFP-UHFFFAOYSA-N alizarin Chemical compound C1=CC=C2C(=O)C3=C(O)C(O)=CC=C3C(=O)C2=C1 RGCKGOZRHPZPFP-UHFFFAOYSA-N 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229930101531 artemisinin Natural products 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000002665 bowman capsule Anatomy 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- OMZCMEYTWSXEPZ-UHFFFAOYSA-N canertinib Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCOCC3)=C(NC(=O)C=C)C=C12 OMZCMEYTWSXEPZ-UHFFFAOYSA-N 0.000 description 1
- 229950002826 canertinib Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000010267 cellular communication Effects 0.000 description 1
- BLUAFEHZUWYNDE-XRNKLDBLSA-N chembl77 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4C31[C@@H]2OC(=O)[C@@H]4C BLUAFEHZUWYNDE-XRNKLDBLSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000003034 chemosensitisation Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 230000002648 chondrogenic effect Effects 0.000 description 1
- 108700004333 collagenase 1 Proteins 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 238000007898 magnetic cell sorting Methods 0.000 description 1
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000003584 mesangial cell Anatomy 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000005055 nestin Anatomy 0.000 description 1
- 210000001178 neural stem cell Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 210000005009 osteogenic cell Anatomy 0.000 description 1
- 230000002188 osteogenic effect Effects 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 210000000557 podocyte Anatomy 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 238000012342 propidium iodide staining Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960001796 sunitinib Drugs 0.000 description 1
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 210000004926 tubular epithelial cell Anatomy 0.000 description 1
- 230000010024 tubular injury Effects 0.000 description 1
- 208000037978 tubular injury Diseases 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000005048 vimentin Anatomy 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cell Biology (AREA)
- Immunology (AREA)
- Developmental Biology & Embryology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Virology (AREA)
- Biotechnology (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP10425052A EP2363136A1 (en) | 2010-03-02 | 2010-03-02 | Microvesicles (MVs) derived from adult stem cells for use in the therapeutic treatment of a tumor disease |
| EP10425052 | 2010-03-02 | ||
| PCT/EP2011/052945 WO2011107437A1 (en) | 2010-03-02 | 2011-02-28 | Microvesicles (mvs) derived from adult stem cells for use in the therapeutic treatment of a tumor disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2554492T3 true ES2554492T3 (es) | 2015-12-21 |
Family
ID=42306621
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11705585.5T Active ES2554492T3 (es) | 2010-03-02 | 2011-02-28 | Microvesículas (MVs) derivadas de citoblastos de etapa adulta para uso en el tratamiento terapéutico de una enfermedad neoplásica. |
Country Status (10)
| Country | Link |
|---|---|
| US (4) | US9717760B2 (enExample) |
| EP (2) | EP2363136A1 (enExample) |
| JP (1) | JP5841952B2 (enExample) |
| CN (1) | CN102781454B (enExample) |
| DK (1) | DK2542250T3 (enExample) |
| ES (1) | ES2554492T3 (enExample) |
| HU (1) | HUE026292T2 (enExample) |
| PL (1) | PL2542250T3 (enExample) |
| PT (1) | PT2542250E (enExample) |
| WO (1) | WO2011107437A1 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2363136A1 (en) * | 2010-03-02 | 2011-09-07 | Fresenius Medical Care Deutschland GmbH | Microvesicles (MVs) derived from adult stem cells for use in the therapeutic treatment of a tumor disease |
| EP2569418B1 (en) | 2010-05-12 | 2016-11-02 | RegenMed (Cayman) Ltd. | Bioactive renal cells |
| ITRM20110403A1 (it) * | 2011-07-28 | 2013-01-29 | Ospedale Pediatrico Bambino Gesu | Microvescicole isolate da cellule mesenchimali come agenti immunosoppressori. |
| CN102357071B (zh) * | 2011-10-26 | 2013-10-23 | 重庆医科大学附属儿童医院 | 载紫杉醇纳米微泡及其制备方法 |
| KR102108245B1 (ko) * | 2011-11-30 | 2020-05-08 | 아스텔라스 인스티튜트 포 리제너러티브 메디슨 | 중간엽 간질 세포 및 이에 관련된 용도 |
| US8961956B2 (en) | 2011-11-30 | 2015-02-24 | Ocata Therapeutics, Inc. | Mesenchymal stromal cells and uses related thereto |
| US11286463B2 (en) | 2012-03-08 | 2022-03-29 | Advanced ReGen Medical Technologies, LLC | Reprogramming of aged adult stem cells |
| CN104471059B (zh) | 2012-07-12 | 2018-04-17 | 珠海横琴爱姆斯坦生物科技有限公司 | 人胚胎干细胞衍生的间充质样干细胞、方法及其应用 |
| WO2015095794A1 (en) | 2013-12-20 | 2015-06-25 | Advanced ReGen Medical Technologies, LLC | Compositions for cellular restoration and methods of making and using same |
| US10772911B2 (en) | 2013-12-20 | 2020-09-15 | Advanced ReGen Medical Technologies, LLC | Cell free compositions for cellular restoration and methods of making and using same |
| EP4445915A3 (en) * | 2014-03-24 | 2025-01-22 | Advanced Regen Medical Technologies, LLC | Cell free compositions for cellular restoration and methods of making and using same |
| WO2015179301A1 (en) * | 2014-05-19 | 2015-11-26 | Eleftherios Papoutsakis | Megakaryocytic particles and microparticles for cell therapy & fate modification of stem and progenitor cells |
| WO2017190000A1 (en) | 2016-04-29 | 2017-11-02 | Advanced ReGen Medical Technologies, LLC | Microrna compositions and methods of making and using same |
| JP7372917B2 (ja) * | 2017-12-14 | 2023-11-01 | ユニシテ エーファウ アクチェンゲゼルシャフト | ｍｉＲＮＡを含有する、腎癌の処置における使用のための薬学的キャリア |
| EP3740576A4 (en) | 2018-01-18 | 2021-10-20 | Advanced Regen Medical Technologies, LLC | THERAPEUTIC COMPOSITIONS AND THEIR PREPARATION AND USE METHODS |
| WO2019197442A1 (en) * | 2018-04-12 | 2019-10-17 | Unicyte Ev Ag | A combination of active ingredients for the treatment of tumor |
| CN111494417B (zh) * | 2020-02-10 | 2024-04-09 | 寇晓星 | 诱导性细胞外囊泡在制备治疗肿瘤药物中的应用 |
| CA3178268A1 (en) | 2020-05-11 | 2021-11-18 | Jonathan Thon | Compositions and methods related to megakaryocyte-derived extracellular vesicles |
| KR102601831B1 (ko) * | 2020-09-23 | 2023-11-14 | 대한민국 | 고형암 증식 억제 효과를 갖는 개과동물의 엑소좀 |
| EP4534649A1 (en) * | 2023-10-03 | 2025-04-09 | Unicyte AG | A method of qualifying as pharmaceutically active a batch of undifferentiated adult stem cells having the potential to differentiate along the hepatic lineage |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6088613A (en) * | 1989-12-22 | 2000-07-11 | Imarx Pharmaceutical Corp. | Method of magnetic resonance focused surgical and therapeutic ultrasound |
| JP2001511775A (ja) * | 1997-01-30 | 2001-08-14 | クワッドラント・ヘルスケア・（ユーケイ）・リミテッド | 微粒子および癌処置での使用 |
| NZ506051A (en) * | 1998-02-09 | 2003-08-29 | Bracco Res S | Targeted delivery of biologically active media |
| US20020177551A1 (en) * | 2000-05-31 | 2002-11-28 | Terman David S. | Compositions and methods for treatment of neoplastic disease |
| US7128903B2 (en) * | 2001-10-03 | 2006-10-31 | Innovative Pharmaceutical Concepts (Ipc) Inc. | Pharmaceutical preparations useful for treating tumors and lesions of the skin and the mucous membranes and methods and kits using same |
| EP1766053A4 (en) * | 2004-06-02 | 2007-12-12 | Sourcepharm Inc | MICROVESICLES CONTAINING RNA AND METHODS |
| US8148335B2 (en) * | 2004-06-23 | 2012-04-03 | Children's Hospital & Research Center Oakland | De-N-acetyl sialic acid antigens, antibodies thereto, and methods of use in cancer therapy |
| GB0501129D0 (en) * | 2005-01-19 | 2005-02-23 | Ribostem Ltd | Method of treatment by administration of RNA |
| WO2006126219A1 (en) | 2005-05-26 | 2006-11-30 | Fresenius Medical Care Deutschland G.M.B.H. | Liver progenitor cells |
| TWI479559B (zh) | 2007-06-28 | 2015-04-01 | Quantum Global Tech Llc | 以選擇性噴灑蝕刻來清潔腔室部件的方法和設備 |
| US8455199B2 (en) * | 2007-09-14 | 2013-06-04 | The Ohio State University Research Foundation | MicroRNA expression in human peripheral blood microvesicles and uses thereof |
| JP5719171B2 (ja) * | 2007-10-15 | 2015-05-13 | フレゼニウス メディカル ケア ドイッチェランド ゲゼルシャフト ミット ベシュレンクテル ハフツング | 内皮細胞移植、特に膵島移植による糖尿病の処置におけるアジュバント活性を有する医薬を調製するための微小胞（ｍｖ）の使用、および関連方法 |
| EP2604271B1 (en) * | 2007-10-29 | 2014-09-17 | Fresenius Medical Care Deutschland GmbH | A stem cell-derived microvesicle (MV) for use in inhibiting apoptosis induced by a cytostatic agent |
| AU2009203638C1 (en) * | 2008-01-04 | 2013-07-25 | Lydac Neuroscience Limited | Microvesicles |
| US20110003008A1 (en) * | 2008-02-22 | 2011-01-06 | Agency For Science, Technology And Research (A*Star) | Mesenchymal stem cell particles |
| EP2186883A1 (en) | 2008-11-04 | 2010-05-19 | Fresenius Medical Care | An isolated multipotent mesenchymal stem cell from human adult glomeruli (hGL-MSC), a method of preparing thereof and uses thereof in the regenerative medicine of the kidney |
| EP2363136A1 (en) * | 2010-03-02 | 2011-09-07 | Fresenius Medical Care Deutschland GmbH | Microvesicles (MVs) derived from adult stem cells for use in the therapeutic treatment of a tumor disease |
-
2010
- 2010-03-02 EP EP10425052A patent/EP2363136A1/en not_active Withdrawn
-
2011
- 2011-02-28 JP JP2012555384A patent/JP5841952B2/ja active Active
- 2011-02-28 ES ES11705585.5T patent/ES2554492T3/es active Active
- 2011-02-28 CN CN201180011925.0A patent/CN102781454B/zh active Active
- 2011-02-28 HU HUE11705585A patent/HUE026292T2/en unknown
- 2011-02-28 PT PT117055855T patent/PT2542250E/pt unknown
- 2011-02-28 WO PCT/EP2011/052945 patent/WO2011107437A1/en not_active Ceased
- 2011-02-28 DK DK11705585.5T patent/DK2542250T3/en active
- 2011-02-28 EP EP11705585.5A patent/EP2542250B1/en active Active
- 2011-02-28 PL PL11705585T patent/PL2542250T3/pl unknown
- 2011-02-28 US US13/581,537 patent/US9717760B2/en active Active
-
2017
- 2017-06-12 US US15/620,164 patent/US10105395B2/en active Active
-
2018
- 2018-09-10 US US16/126,364 patent/US20190060369A1/en not_active Abandoned
-
2023
- 2023-04-17 US US18/135,243 patent/US20230248774A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP2542250B1 (en) | 2015-08-26 |
| JP2013520971A (ja) | 2013-06-10 |
| EP2363136A1 (en) | 2011-09-07 |
| JP5841952B2 (ja) | 2016-01-13 |
| HUE026292T2 (en) | 2016-05-30 |
| US20170348356A1 (en) | 2017-12-07 |
| DK2542250T3 (en) | 2015-12-07 |
| PL2542250T3 (pl) | 2016-04-29 |
| CN102781454B (zh) | 2015-12-16 |
| US20190060369A1 (en) | 2019-02-28 |
| CN102781454A (zh) | 2012-11-14 |
| US20230248774A1 (en) | 2023-08-10 |
| PT2542250E (pt) | 2015-12-09 |
| EP2542250A1 (en) | 2013-01-09 |
| US9717760B2 (en) | 2017-08-01 |
| US10105395B2 (en) | 2018-10-23 |
| WO2011107437A1 (en) | 2011-09-09 |
| US20120321723A1 (en) | 2012-12-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2554492T3 (es) | Microvesículas (MVs) derivadas de citoblastos de etapa adulta para uso en el tratamiento terapéutico de una enfermedad neoplásica. | |
| JP5261494B2 (ja) | 損傷しまたは傷害を受けた組織または臓器の内皮／上皮再生用医薬の製造のための、幹細胞由来微小胞（ｍｖ）の使用ならびにインビトロおよびインビボでの関連した方法 | |
| Meier et al. | Microencapsulated human mesenchymal stem cells decrease liver fibrosis in mice | |
| Mund et al. | Endothelial progenitor cells and cardiovascular cell-based therapies | |
| EP2554176B1 (en) | Means for liver regeneration | |
| DK2736600T3 (en) | Microvesicles isolated from mesenchymal stem cells for use as immunosuppressive agents | |
| JP5719171B2 (ja) | 内皮細胞移植、特に膵島移植による糖尿病の処置におけるアジュバント活性を有する医薬を調製するための微小胞（ｍｖ）の使用、および関連方法 | |
| Li et al. | Autologous bone marrow-derived mesenchymal stem cell transplantation promotes liver regeneration after portal vein embolization in cirrhotic rats | |
| Enoki et al. | Enhanced mesenchymal cell engraftment by IGF-1 improves left ventricular function in rats undergoing myocardial infarction | |
| Wood et al. | Distinct contribution of human cord blood‐derived endothelial colony forming cells to liver and gut in a fetal sheep model | |
| JP7029729B2 (ja) | 血管障害の予防又は治療剤 | |
| KR20160034176A (ko) | Oct4 및 Sox2를 과발현하는 중간엽줄기세포 및 그 용도 | |
| Chae et al. | Efficacy and safety of human bone marrow-derived mesenchymal stem cells according to injection route and dose in a chronic kidney disease rat model | |
| JP5686841B2 (ja) | 損傷しまたは傷害を受けた組織または臓器の内皮／上皮再生用医薬の製造のための、幹細胞由来微小胞（ｍｖ）の使用ならびにインビトロおよびインビボでの関連した方法 | |
| RU2334793C1 (ru) | Способ получения культуры клеток с индуцированным ангиогенным фенотипом, предназначенной для тканевой инженерии в зоне ишемии | |
| Ibrahim et al. | The therapeutic effect of mesenchymal stem cells on kidney and iNOS expression in hypoxic male rats | |
| WO2011154505A2 (en) | Complex product comprising a cellular carrier and a cytoxic chemotherapeutic drug | |
| Nguyen | Salivary forming unit isolation and culture | |
| WO2005014016A1 (en) | Compositions containing macrophages and uses thereof |