JPWO2021207282A5 - - Google Patents
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- JPWO2021207282A5 JPWO2021207282A5 JP2022561111A JP2022561111A JPWO2021207282A5 JP WO2021207282 A5 JPWO2021207282 A5 JP WO2021207282A5 JP 2022561111 A JP2022561111 A JP 2022561111A JP 2022561111 A JP2022561111 A JP 2022561111A JP WO2021207282 A5 JPWO2021207282 A5 JP WO2021207282A5
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- 239000002676 xenobiotic agent Substances 0.000 claims 1
- 230000002034 xenobiotic effect Effects 0.000 claims 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims 1
- 102000007299 Amphiregulin Human genes 0.000 description 4
- 102000001327 Chemokine CCL5 Human genes 0.000 description 1
- 102000004264 Osteopontin Human genes 0.000 description 1
Description
いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、約４．７～約７．５のｐＨを有する。 In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization has a pH of about 4.7 to about 7.5.
いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、張性改変剤をさらに含む。 In some embodiments, the lyophilized and/or lyophilized MSC secretome composition further comprises a tonicity modifying agent.
いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、アンジオポエチン－１、アンジオポエチン－２、アンフィレグリン、エンドスタチン、エンドセリン－１、トロンボスポンジン－２、及びトロンボスポンジン－１、アンギオゲニン、ＤＰＰＩＶ（ジペプチジルペプチダーゼ－４）、ＩＧＦＢＰ－３、及び／またはｕＰＡを含むがこれらに限定されない少なくとも１つの因子の「中程度」レベルをさらに含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、アンジオポエチン－１、アンジオポエチン－２、アンフィレグリン、エンドスタチン、エンドセリン－１、トロンボスポンジン－２、及びトロンボスポンジン－１、アンギオゲニン、ＤＰＰＩＶ、ＩＧＦＢＰ－３、ならびにｕＰＡからなる群から選択される「中程度」レベルの少なくとも１つの因子をさらに含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、アンギオゲニン、ＤＰＰＩＶ、ＩＧＦＢＰ－３、及びｕＰＡからなる群から選択される少なくとも１つの因子の「中程度」レベルをさらに含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、約２００ｐｇ／ｍＬ～約８００ｐｇ／ｍＬの、アンギオゲニン、ＤＰＰＩＶ、ＩＧＦＢＰ－３、及びｕＰＡからなる群から選択される少なくとも１つの因子をさらに含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、約２００ｐｇ／ｍＬ～約７００ｐｇ／ｍＬ、約３００ｐｇ／ｍＬ～約８００ｐｇ／ｍＬ、約２００ｐｇ／ｍＬ～約５００ｐｇ／ｍＬ、または約３００ｐｇ／ｍＬ～約５００ｐｇ／ｍＬの、アンジオポエチン－１、アンジオポエチン－２、アンフィレグリン、エンドスタチン、エンドセリン－１、トロンボスポンジン－２、及びトロンボスポンジン－１、アンギオゲニン、ＤＰＰＩＶ、ＩＧＦＢＰ－３及びｕＰＡからなる群から選択される少なくとも１つの因子をさらに含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、約２００ｐｇ／ｍＬ、約３００ｐｇ／ｍＬ、約４００ｐｇ／ｍＬ、約５００ｐｇ／ｍＬ、約６００ｐｇ／ｍＬ、約７００ｐｇ／ｍＬ、または約８００ｐｇ／ｍＬの、アンジオポエチン－１、アンジオポエチン－２、アンフィレグリン、エンドスタチン、エンドセリン－１、トロンボスポンジン－２、及びトロンボスポンジン－１、アンギオゲニン、ＤＰＰＩＶ、ＩＧＦＢＰ－３、及びｕＰＡからなる群から選択される少なくとも１つの因子をさらに含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、約２００ｐｇ／ｍＬ～約８００ｐｇ／ｍＬ、約３００ｐｇ／ｍＬ～８００ｐｇ／ｍＬ、約２００ｐｇ／ｍＬ～約５００ｐｇ／ｍＬ、または約３００ｐｇ／ｍＬ～約５００ｐｇ／ｍＬのアンギオゲニンを含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、約２００ｐｇ／ｍＬ～約８００ｐｇ／ｍＬ、約３００ｐｇ／ｍＬ～約８００ｐｇ／ｍＬ、約２００ｐｇ／ｍＬ～約５００ｐｇ／ｍＬ、または約３００ｐｇ／ｍＬ～約５００ｐｇ／ｍＬのＤＰＰＩＶをさらに含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、約２００ｐｇ／ｍＬ～約８００ｐｇ／ｍＬ、約３００ｐｇ／ｍＬ～約８００ｐｇ／ｍＬ、約２００ｐｇ／ｍＬ～５００ｐｇ／ｍＬ、または約３００ｐｇ／ｍＬ～約５００ｐｇ／ｍＬのＩＧＦＢＰ－３を含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、２００ｐｇ／ｍＬ～約８００ｐｇ／ｍＬ、約３００ｐｇ／ｍＬ～８００ｐｇ／ｍＬ、約２００ｐｇ／ｍＬ～５００ｐｇ／ｍＬ、または約３００ｐｇ／ｍＬ～約５００ｐｇ／ｍＬのｕＰＡを含む。 In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization further comprises a "moderate" level of at least one factor including, but not limited to, angiopoietin-1, angiopoietin-2, amphiregulin, endostatin, endothelin-1, thrombospondin-2, and thrombospondin-1, angiogenin, DPPIV (dipeptidyl peptidase-4), IGFBP-3, and/or uPA. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization further comprises a "moderate" level of at least one factor selected from the group consisting of angiopoietin-1, angiopoietin-2, amphiregulin, endostatin, endothelin-1, thrombospondin-2, and thrombospondin-1, angiogenin, DPPIV, IGFBP-3, and uPA. In some embodiments, the lyophilized and/or lyophilized MSC secretome composition further comprises a "moderate" level of at least one factor selected from the group consisting of angiogenin, DPPIV, IGFBP-3, and uPA. In some embodiments, the lyophilized and/or lyophilized MSC secretome composition further comprises about 200 pg/mL to about 800 pg/mL of at least one factor selected from the group consisting of angiogenin, DPPIV, IGFBP-3, and uPA. In some embodiments, the lyophilized and/or lyophilized MSC secretome composition further comprises about 200 pg/mL to about 700 pg/mL, about 300 pg/mL to about 800 pg/mL, about 200 pg/mL to about 500 pg/mL, or about 300 pg/mL to about 500 pg/mL of at least one factor selected from the group consisting of angiopoietin-1, angiopoietin-2, amphiregulin, endostatin, endothelin-1, thrombospondin-2, and thrombospondin-1, angiogenin, DPPIV, IGFBP-3, and uPA. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization further comprises about 200 pg/mL, about 300 pg/mL, about 400 pg/mL, about 500 pg/mL, about 600 pg/mL, about 700 pg/mL, or about 800 pg/mL of at least one factor selected from the group consisting of angiopoietin-1, angiopoietin-2, amphiregulin, endostatin, endothelin-1, thrombospondin-2, and thrombospondin-1, angiogenin, DPPIV, IGFBP-3, and uPA. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization comprises about 200 pg/mL to about 800 pg/mL, about 300 pg/mL to about 800 pg/mL, about 200 pg/mL to about 500 pg/mL, or about 300 pg/mL to about 500 pg/mL angiogenin. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization further comprises about 200 pg/mL to about 800 pg/mL, about 300 pg/mL to about 800 pg/mL, about 200 pg/mL to about 500 pg/mL, or about 300 pg/mL to about 500 pg/mL DPPIV. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization comprises about 200 pg/mL to about 800 pg/mL, about 300 pg/mL to about 800 pg/mL, about 200 pg/mL to 500 pg/mL, or about 300 pg/mL to about 500 pg/mL IGFBP-3. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization comprises about 200 pg/mL to about 800 pg/mL, about 300 pg/mL to 800 pg/mL, about 200 pg/mL to 500 pg/mL, or about 300 pg/mL to about 500 pg/mL uPA.
凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物のいくつかの実施形態では、ＶＥＧＦのレベルは、セルピンＥ１のレベルより５～１０倍低い。凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物のいくつかの実施形態では、ＶＥＧＦのレベルは、セルピンＥ１のレベルよりも６～１０倍低い。凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物のいくつかの実施形態では、ＶＥＧＦのレベルは、セルピンＥ１のレベルより７～１０倍低い。凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物のいくつかの実施形態では、ＶＥＧＦのレベルは、セルピンＥ１のレベルよりも８～１０倍低い。凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物のいくつかの実施形態では、ＶＥＧＦのレベルは、セルピンＥ１のレベルより９～１０倍低い。凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物のいくつかの実施形態では、ＶＥＧＦのレベルは、セルピンＥ１のレベルより５倍低い。凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物のいくつかの実施形態では、ＶＥＧＦのレベルは、セルピンＥ１のレベルより６倍低い。凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物のいくつかの実施形態では、ＶＥＧＦのレベルは、セルピンＥ１のレベルより７倍低い。凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物のいくつかの実施形態では、ＶＥＧＦのレベルは、セルピンＥ１のレベルよりも８倍低い。凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物のいくつかの実施形態では、ＶＥＧＦのレベルは、セルピンＥ１のレベルよりも９倍低い。凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物のいくつかの実施形態では、ＶＥＧＦのレベルは、セルピンＥ１のレベルよりも１０倍低い。 In some embodiments of the MSC secretome composition for lyophilization and/or after lyophilization, the level of VEGF is 5-10 fold lower than the level of serpin E1. In some embodiments of the MSC secretome composition for lyophilization and/or after lyophilization, the level of VEGF is 6-10 fold lower than the level of serpin E1. In some embodiments of the MSC secretome composition for lyophilization and/or after lyophilization, the level of VEGF is 7-10 fold lower than the level of serpin E1. In some embodiments of the MSC secretome composition for lyophilization and/or after lyophilization, the level of VEGF is 8-10 fold lower than the level of serpin E1. In some embodiments of the MSC secretome composition for lyophilization and/or after lyophilization, the level of VEGF is 9-10 fold lower than the level of serpin E1. In some embodiments of the MSC secretome composition for lyophilization and/or after lyophilization, the level of VEGF is 5 fold lower than the level of serpin E1. In some embodiments of the MSC secretome composition for lyophilization and/or after lyophilization, the level of VEGF is 6-fold lower than the level of serpin E1. In some embodiments of the MSC secretome composition for lyophilization and/or after lyophilization, the level of VEGF is 7-fold lower than the level of serpin E1. In some embodiments of the MSC secretome composition for lyophilization and/or after lyophilization, the level of VEGF is 8-fold lower than the level of serpin E1. In some embodiments of the MSC secretome composition for lyophilization and/or after lyophilization, the level of VEGF is 9-fold lower than the level of serpin E1. In some embodiments of the MSC secretome composition for lyophilization and/or after lyophilization, the level of VEGF is 10-fold lower than the level of serpin E1.
いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、ｂＦＧＦ、ＰＬＧＦ、及びＰＤＧＦを含まない、及び／または非常に低レベルで含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、約２００ｐｇ／ｍＬ未満、約１５０ｐｇ／ｍＬ未満、約１００ｐｇ／ｍＬ未満、約７５ｐｇ／ｍＬ未満、約５０ｐｇ／ｍＬ未満、または約２５ｐｇ／ｍＬ未満のｂＦＧＦ、ＰＬＧＦ、及び／またはＰＤＧＦを含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、約２００ｐｇ／ｍＬ未満、約１５０ｐｇ／ｍＬ未満、約１００ｐｇ／ｍＬ未満、約７５ｐｇ／ｍＬ未満、約５０ｐｇ／ｍＬ未満、または約２５ｐｇ／ｍＬ未満のｂＦＧＦ、ＰＬＧＦ、及びＰＤＧＦを含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、ｂＦＧＦ、ＰＬＧＦ、及び／またはＰＤＧＦを含まない。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、ｂＦＧＦ、ＰＬＧＦ、及びＰＤＧＦを含まない。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、約２００ｐｇ／ｍＬ未満、約１５０ｐｇ／ｍＬ未満、約１００ｐｇ／ｍＬ未満、約７５ｐｇ／ｍＬ未満、約５０ｐｇ／ｍＬ未満、または約２５ｐｇ／ｍＬ未満のｂＦＧＦを含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、ｂＦＧＦを含まない。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、約２００ｐｇ／ｍＬ未満、約１５０ｐｇ／ｍＬ未満、約１００ｐｇ／ｍＬ未満、約７５ｐｇ／ｍＬ未満、約５０ｐｇ／ｍＬ未満、または約２５ｐｇ／ｍＬ未満のＰＬＧＦを含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、ＰＬＧＦを含まない。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、約２００ｐｇ／ｍＬ未満、約１５０ｐｇ／ｍＬ未満、約１００ｐｇ／ｍＬ未満、約７５ｐｇ／ｍＬ未満、約５０ｐｇ／ｍＬ未満、または約２５ｐｇ／ｍＬ未満のＰＤＧＦを含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、ＰＤＧＦを含まない。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、ｂＦＧＦを含まない。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、ＰＬＧＦを含まない。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、ＰＤＧＦを含まない。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、非常に低レベルのｂＦＧＦ、ＰＬＧＦ、及びＰＤＧＦを含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、非常に低レベルのｂＦＧＦを含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、非常に低レベルのＰＬＧＦを含む。いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、非常に低レベルのＰＤＧＦを含む。 In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization is free of and/or contains very low levels of bFGF, PLGF, and PDGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization contains less than about 200 pg/mL, less than about 150 pg/mL, less than about 100 pg/mL, less than about 75 pg/mL, less than about 50 pg/mL, or less than about 25 pg/mL of bFGF, PLGF, and/or PDGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization contains less than about 200 pg/mL, less than about 150 pg/mL, less than about 100 pg/mL, less than about 75 pg/mL, less than about 50 pg/mL, or less than about 25 pg/mL of bFGF, PLGF, and PDGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization does not include bFGF, PLGF, and/or PDGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization does not include bFGF, PLGF, and PDGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization includes less than about 200 pg/mL, less than about 150 pg/mL, less than about 100 pg/mL, less than about 75 pg/mL, less than about 50 pg/mL, or less than about 25 pg/mL bFGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization does not include bFGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization comprises less than about 200 pg/mL, less than about 150 pg/mL, less than about 100 pg/mL, less than about 75 pg/mL, less than about 50 pg/mL, or less than about 25 pg/mL PLGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization does not comprise PLGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization comprises less than about 200 pg/mL, less than about 150 pg/mL, less than about 100 pg/mL, less than about 75 pg/mL, less than about 50 pg/mL, or less than about 25 pg/mL PDGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization does not comprise PDGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization does not comprise bFGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization does not include PLGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization does not include PDGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization includes very low levels of bFGF, PLGF, and PDGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization includes very low levels of bFGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization includes very low levels of PLGF. In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization includes very low levels of PDGF.
いくつかの実施形態では、凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物は、アポリポタンパク質Ａ１、補体因子Ｄ、Ｃ反応性タンパク質、シスタチンＣ、ＤＫＫ－１、エンプリン、オステオポンチン、ビタミンＤＢＰ、ＭＩＦ、ＲＡＮＴＥＳ、ｕＰＡＲ、ＩＬ－１７ａ、ＧＤＦ－１５及び／またはＩＦＮγを含む。 In some embodiments, the MSC secretome composition for lyophilization and/or after lyophilization comprises apolipoprotein A1, complement factor D, C-reactive protein, cystatin C, DKK-1, EMMPRIN, osteopontin, vitamin DBP, MIF, RANTES, uPAR, IL-17a, GDF-15, and/or IFNγ.
Claims (16)
ａ．ＨＧＦ、ＴＩＭＰ－１、ＴＩＭＰ－２、ＰＡＩ－１（セルピンＥ１）、ＶＥＧＦ－Ａ、及びｂ－ＮＧＦからなる群から選択される少なくとも１つの栄養因子／サイトカインと、
ｂ．ＰＥＤＦ（セルピンＦ１）、ＩＧＦＢＰ－２、ＩＧＦＢＰ－３、ＳＤＦ－１、ＴＳＧ－１４、カリクレイン３、ＭＣＰ－１、アンギオゲニン、ＭＣＰ－２、アンギオ－２、ＩＬ－６、ＩＬ－１７、Ｇ－ＣＳＦ、Ｍ－ＣＳＦ、ＧＭ－ＣＳＦ、ＩＬ－８、ＴＮＦ－ベータ、及びＰＤＧＦからなるグループから選択される少なくとも１つの追加因子と、
ｃ．ＤＰＰＩＶ（ジペプチジルペプチダーゼ－４）、ｕＰＡ、アンジオポエチン－１、アンジオポエチン－２、アンフィレグリン、エンドスタチン、エンドセリン－１、トロンボスポンジン－２、及びトロンボスポンジン－１からなる群から選択される少なくとも１つの追加因子と、を含む、請求項１に記載の凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物。 A composition of MSC secretome for lyophilization and/or after lyophilization, comprising:
a. at least one trophic factor/cytokine selected from the group consisting of HGF, TIMP-1, TIMP-2, PAI-1 (serpin E1), VEGF-A, and b-NGF;
b. at least one additional factor selected from the group consisting of PEDF (serpin F1), IGFBP-2, IGFBP-3, SDF-1, TSG-14, kallikrein 3, MCP-1, angiogenin, MCP-2, angio-2, IL-6, IL-17, G-CSF, M-CSF, GM-CSF, IL-8, TNF-beta, and PDGF;
and c) at least one additional factor selected from the group consisting of DPPIV (dipeptidyl peptidase-4), uPA, angiopoietin-1, angiopoietin-2, amphiregulin, endostatin, endothelin- 1 , thrombospondin-2, and thrombospondin-1.
ｂ）凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物が、１ｎｇ／ｍＬ～４００ｎｇ／ｍＬの、セルピンＥ１、セルピンＡ１、ＴＩＭＰ－１、トロンボスポンジン－１、ペントラキシン－３（ＴＳＧ－１４）、血小板第４因子及びセルピンＦ１からなる群から選択される少なくとも１つの因子を含む；および／または
ｃ）凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物が、「中程度」レベルの、アンジオポエチン－１、アンジオポエチン－２、アンフィレグリン、エンドスタチン、エンドセリン－１、トロンボスポンジン－２、トロンボスポンジン－１、アンギオゲニン、ＤＰＰＩＶ、ＩＧＦＢＰ－３、及び／またはｕＰＡからなる群から選択される少なくとも１つの因子をさらに含む；および／または
ｄ）ＭＳＣセクレトーム組成物が、４００ｐｇ／ｍＬ～３０００ｐｇ／ｍＬの、アンジオポエチン－１、アンジオポエチン－２、アンフィレグリン、エンドスタチン、エンドセリン－１、トロンボスポンジン－２、トロンボスポンジン－１、アンギオゲニン、ＤＰＰＩＶ、ＩＧＦＢＰ－３、及びｕＰＡからなる群から選択される少なくとも１つの因子を含む；および／または
ｅ）凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物が、アポリポタンパク質Ａ１、補体因子Ｄ、Ｃ反応性タンパク質、シスタチンＣ、ＤＫＫ－１、エンプリン、オステオポンチン、ビタミンＤＢＰ、ＭＩＦ、ＲＡＮＴＥＳ、ｕＰＡＲ、ＩＬ－１７ａ、ＧＤＦ－１５、及びＩＦＮγからなる群から選択される少なくとも１つの因子をさらに含む；および／または
ｆ）凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物が、抗血管新生因子対血管新生促進因子を、＞２、＞３、＞４、または＞５の比の値で含む；および／または
ｇ）抗血管新生因子が、ＰＥＤＦ、低レベルのＶＥＧＦ、及びセルピンＥ１からなる群から選択される１つ以上の因子を含み、前記血管新生促進因子は、ＶＥＧＦ、アンギオゲニン、ＩＧＦＢＰ－３、ｕＰＡ、アンギオ－１、アンギオ－２、エンドセリン－１からなる群から選択される１つ以上の因子を含む；および／または
ｈ）凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物が、低レベルのＶＥＧＦをさらに含む；および／または
ｉ）凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物が、１ｐｇ／ｍＬ～４００ｐｇ／ｍＬのＶＥＧＦを含む；および／または
ｊ）ＶＥＧＦのレベルが、前記セルピンＥ１のレベルより５～１０倍低い；および／または
ｋ）組成物が、１つ以上の抗血管新生因子を含み、前記ＶＥＧＦの濃度に対する前記１つ以上の抗血管新生因子の濃度の合計が＞２、＞３、＞４、または＞５である；および／または
ｌ）凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物が、ｂＦＧＦ、ＰＬＧＦ、及びＰＤＧＦを含まない、及び／または非常に低レベルで含む；および／または
ｍ）ＭＳＣセクレトームが、１０００ｐｇ／ｍＬ未満のｂＦＧＦ、ＰＬＧＦ、及びＰＤＧＦを含む；および／または
ｎ）凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物が、約４．７～約７．５のｐＨを有する；および／または
ｏ）凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物が、リン酸二ナトリウム／一ナトリウム、クエン酸ナトリウム／クエン酸、ホウ酸／クエン酸ナトリウム、ホウ酸／四ホウ酸ナトリウム、及びクエン酸／リン酸二ナトリウムからなる群から選択される緩衝系で配合される；および／または
ｐ）凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物が張性改変剤をさらに含み、要すれば、前記張性改変剤が、ＮａＣｌ、ＫＣｌ、マンニトール、デキストロース、スクロース、ソルビトール、及びグリセリンからなる群から選択される；および／または
ｑ）凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物が、リン酸一ナトリウム／二ナトリウム、マンニトール、及びトレハロースをさらに含み、前記組成物が約ｐＨ７．４のｐＨを有する；および／または
ｒ）凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物が、二価カチオンをさらに含み、要すれば、前記二価カチオンが、Ｍｇ２ ＋ 、Ｃａ２ ＋ 、及びＺｎ２ ＋ からなる群から選択される；および／または
ｓ）凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物が、リン酸二ナトリウム／クエン酸、マンニトール、及びトレハロースをさらに含み、前記組成物が約ｐＨ６．４のｐＨを有する；および／または
ｔ）凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物が、接着剤をさらに含み、要すれば、前記接着剤が、ヒプロメロース、ポロキサマー４０７、ポロキサマー１８８、ポロキソマー２３７、ポロキソマー３３８、ヒプロメロース（ＨＰＭＣ）、ポリカルボフィル、ポリビニルピロリドン（ＰＶＰ）、ＰＶＡ（ポリビニルアルコール）、ポリイミド、ヒアルロン酸ナトリウム、ジェランガム、ポリ（乳酸－コ－グリコール酸）（ＰＬＧＡ）、ポリシロキサン、ポリイミド、カルボキシメチルセルロース（ＣＭＣ）、またはヒドロキシプロピルメチルセルロース（ＨＰＭＣ）、ヒドロキシメチルセルロース、ヒドロキシエチルセルロース、ナトリウムカルボキシメチルセルロース、フィブリン接着剤、ポリエチレングリコール、ＧｅｌＣＯＲＥからなる群から選択される；および／または
ｕ）凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物が、生体異物成分、フェノールレッド、ペプチド及び生体分子＜３ｋＤａ、抗生物質、タンパク質凝集体＞２００ｎｍ、細胞、非エクソソーム／非細胞外小胞細胞破片、ホルモン、及びＬ－グルタミンからなる群から選択される１つ以上の成分を含まない、
請求項１または２に記載の凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物。 a) the lyophilized and/or lyophilized MSC secretome composition further comprises elevated levels of at least one factor selected from the group consisting of serpin E1, serpin A1, TIMP-1, thrombospondin-1, pentraxin-3 (TSG-14), platelet factor 4, and serpin F1 ; and/or
b) the lyophilized and/or lyophilized MSC secretome composition comprises 1 ng/mL to 400 ng/mL of at least one factor selected from the group consisting of serpin E1, serpin A1, TIMP-1, thrombospondin-1, pentraxin-3 (TSG-14), platelet factor 4, and serpin F1; and/or
c) the lyophilized and/or lyophilized MSC secretome composition further comprises a "moderate" level of at least one factor selected from the group consisting of angiopoietin-1, angiopoietin-2, amphiregulin, endostatin, endothelin-1, thrombospondin-2, thrombospondin-1, angiogenin, DPPIV, IGFBP-3, and/or uPA; and/or
d) the MSC secretome composition comprises 400 pg/mL to 3000 pg/mL of at least one factor selected from the group consisting of angiopoietin-1, angiopoietin-2, amphiregulin, endostatin, endothelin-1, thrombospondin-2, thrombospondin-1, angiogenin, DPPIV, IGFBP-3, and uPA; and/or
e) the lyophilized and/or lyophilized MSC secretome composition further comprises at least one factor selected from the group consisting of apolipoprotein A1, complement factor D, C-reactive protein, cystatin C, DKK-1, EMMPRIN, osteopontin, vitamin DBP, MIF, RANTES, uPAR, IL-17a, GDF-15, and IFNγ; and/or
f) the MSC secretome composition for lyophilization and/or after lyophilization comprises anti-angiogenic factors to pro-angiogenic factors at a ratio value of >2, >3, >4, or >5; and/or
g) the anti-angiogenic factors include one or more factors selected from the group consisting of PEDF, low levels of VEGF, and serpin E1, and the pro-angiogenic factors include one or more factors selected from the group consisting of VEGF, angiogenin, IGFBP-3, uPA, angio-1, angio-2, endothelin-1; and/or
h) the lyophilized and/or lyophilized MSC secretome composition further comprises low levels of VEGF; and/or
i) the MSC secretome composition for lyophilization and/or after lyophilization comprises 1 pg/mL to 400 pg/mL VEGF; and/or
j) the level of VEGF is 5-10 fold lower than the level of said Serpin E1; and/or
k) the composition comprises one or more anti-angiogenic factors, and the sum of the concentrations of the one or more anti-angiogenic factors relative to the concentration of the VEGF is >2, >3, >4, or >5; and/or
l) the MSC secretome composition for lyophilization and/or after lyophilization is free of and/or contains very low levels of bFGF, PLGF, and PDGF; and/or
m) the MSC secretome contains less than 1000 pg/mL bFGF, PLGF, and PDGF; and/or
n) the lyophilized and/or lyophilized MSC secretome composition has a pH of about 4.7 to about 7.5; and/or
o) the lyophilized and/or lyophilized MSC secretome composition is formulated with a buffer system selected from the group consisting of disodium phosphate/monosodium, sodium citrate/citric acid, boric acid/sodium citrate, boric acid/sodium tetraborate, and citric acid/disodium phosphate; and/or
p) the lyophilized and/or lyophilized MSC secretome composition further comprises a tonicity modifying agent, optionally selected from the group consisting of NaCl, KCl, mannitol, dextrose, sucrose, sorbitol, and glycerin; and/or
q) the lyophilized and/or lyophilized MSC secretome composition further comprises mono/di-sodium phosphate, mannitol, and trehalose, said composition having a pH of about pH 7.4; and/or
r) the lyophilized and/or lyophilized MSC secretome composition further comprises a divalent cation, optionally selected from the group consisting of Mg2 + , Ca2 + , and Zn2 + ; and/or
s) the lyophilized and/or lyophilized MSC secretome composition further comprises disodium phosphate/citric acid, mannitol, and trehalose, said composition having a pH of about pH 6.4; and/or
t) the lyophilized and/or lyophilized MSC secretome composition further comprises an adhesive, optionally selected from the group consisting of hypromellose, poloxamer 407, poloxamer 188, poloxomer 237, poloxomer 338, hypromellose (HPMC), polycarbophil, polyvinylpyrrolidone (PVP), PVA (polyvinyl alcohol), polyimide, sodium hyaluronate, gellan gum, poly(lactic-co-glycolic acid) (PLGA), polysiloxane, polyimide, carboxymethylcellulose (CMC), or hydroxypropylmethylcellulose (HPMC), hydroxymethylcellulose, hydroxyethylcellulose, sodium carboxymethylcellulose, fibrin adhesive, polyethylene glycol, GelCORE; and/or
u) the MSC secretome composition for lyophilization and/or after lyophilization is free of one or more components selected from the group consisting of xenobiotic components, phenol red, peptides and biomolecules <3 kDa, antibiotics, protein aggregates >200 nm, cells, non-exosomes/non-extracellular vesicle cell debris, hormones, and L-glutamine;
The freeze-dried and/or freeze-dried MSC secretome composition according to claim 1 or 2 .
ｉ．０．３～４．５ｎｇ／ｍＬのＨＧＦと、
ｉｉ．０．５～２０ｎｇ／ｍＬのペントラキシン－３（ＴＳＧ－１４）と、
ｉｉｉ．１００～６００ｐｇ／ｍＬのＶＥＧＦと、
ｉｖ．１０～２００ｎｇ／ｍＬのＴＩＭＰ－１と、
ｖ．２０～８０ｎｇ／ｍＬのセルピンＥ１と、
ｖｉ．＜５ｎｇ／ｍＬのＩＬ－８と、を含む、請求項１から３のいずれか一項に記載の凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物。 2. The composition of claim 1, further comprising:
i. 0.3-4.5 ng/mL HGF;
ii. 0.5-20 ng/mL of pentraxin-3 (TSG-14);
iii. 100-600 pg/mL VEGF;
iv. 10-200 ng/mL TIMP-1;
v. 20-80 ng/mL of serpin E1;
vi. <5 ng / mL IL-8.
ｉ．０．３～４．５ｎｇ／ｍＬのＨＧＦと、
ｉｉ．０．５～２０ｎｇ／ｍＬのペントラキシン－３（ＴＳＧ－１４）と、
ｉｉｉ．１００～６００ｐｇ／ｍＬのＶＥＧＦと、
ｉｖ．１０～２００ｎｇ／ｍＬのＴＩＭＰ－１と、
ｖ．２０～８０ｎｇ／ｍＬのセルピンＥ１と
ｖｉ．１００～４００ｎｇ／ｍＬのセルピンＦ１と、
ｖｉｉ．＜５ｎｇ／ｍＬのＩＬ－８と、を含む、請求項１から４のいずれか一項に記載の凍結乾燥用及び／または凍結乾燥後のＭＳＣセクレトーム組成物。 2. The composition of claim 1, further comprising:
i. 0.3-4.5 ng/mL HGF;
ii. 0.5-20 ng/mL of pentraxin-3 (TSG-14);
iii. 100-600 pg/mL VEGF;
iv. 10-200 ng/mL TIMP-1;
v. 20-80 ng/mL of serpin E1; and vi. 100-400 ng/mL of serpin F1;
vii. The lyophilized and/or lyophilized MSC secretome composition of any one of claims 1 to 4 , comprising <5 ng/mL IL-8.
ｉ．１ｍＬあたり２μｇ～２０μｇのＭＳＣセクレトームと、
ｉｉ．１ｍＬあたり２ｍｇ～３ｍｇの一塩基性リン酸ナトリウムと、
ｉｉｉ．１ｍＬあたり１１ｍｇ～１２ｍｇの二塩基性リン酸ナトリウムと、
ｉｖ．１ｍＬあたり１１．５ｍｇ～１３ｍｇのマンニトールと、
ｖ．２３ｍｇ～２４ｍｇのトレハロース二水和物と、
ｖｉ．１ｍＬあたり０．５ｍｇ～２ｍｇの任意選択のヒプロメロースと、を含み、
ｐＨは約４．７～約７．５である、
凍結乾燥用及び／または凍結乾燥後の安定した間葉系幹細胞（ＭＳＣ）セクレトーム製剤。 1. A stable mesenchymal stem cell (MSC) secretome formulation for and/or after lyophilization, comprising:
i. 2 μg to 20 μg of MSC secretome per mL;
ii. 2 mg to 3 mg per mL of sodium phosphate monobasic;
iii. 11 mg to 12 mg per mL of dibasic sodium phosphate;
iv. 11.5 mg to 13 mg of mannitol per mL;
v. 23 mg to 24 mg of trehalose dihydrate;
vi. 0.5 mg to 2 mg of optional hypromellose per mL;
The pH is from about 4.7 to about 7.5 ;
A stable mesenchymal stem cell (MSC) secretome preparation for and/or after lyophilization .
ｉ．０．００４％～０．０８％ｗ／ｗのＭＳＣセクレトームと、
ｉｉ．４％～５％ｗ／ｗの一塩基性リン酸ナトリウムと、
ｉｉｉ．２１．５％～２３％ｗ／ｗの二塩基性リン酸ナトリウムと、
ｉｖ．２３％～２５％ｗ／ｗのマンニトールと、
ｖ．４６％～４８％ｗ／ｗのトレハロース脱水と、
ｖｉ．１％～３％ｗ／ｗの任意選択のヒプロメロースと、を含み、
ｐＨは約４．７～約７．５である、
凍結乾燥用及び／または凍結乾燥後の安定した間葉系幹細胞（ＭＳＣ）セクレトーム製剤。 1. A stable mesenchymal stem cell (MSC) secretome formulation for and/or after lyophilization, comprising:
i. 0.004%-0.08% w/w MSC secretome;
ii. 4% to 5% w/w of sodium phosphate monobasic;
iii. 21.5% to 23% w/w of dibasic sodium phosphate;
iv. 23% to 25% w/w mannitol;
v. 46% to 48% w/w trehalose dehydrate;
vi. 1%-3% w/w of optional hypromellose;
The pH is from about 4.7 to about 7.5 ;
A stable mesenchymal stem cell (MSC) secretome preparation for and/or after lyophilization .
ｉ．１ｍＬあたり２μｇ－２０μｇのＭＳＣセクレトームと、
ｉｉ．１ｍＬあたり２ｍｇ～３ｍｇの一塩基性リン酸ナトリウムと、
ｉｉｉ．１ｍＬあたり１１ｍｇ～１２ｍｇの二塩基性リン酸ナトリウムと、
ｉｖ．１ｍＬあたり１１．５ｍｇ～１３ｍｇのマンニトールと、
ｖ．２３ｍｇ～２４ｍｇのトレハロース二水和物と、
ｖｉ．１ｍＬあたり０．５ｍｇ～２ｍｇの任意選択のヒプロメロースと、を含み、
ｐＨは約４．７～約７．５である、
再構成凍結乾燥ＭＳＣセクレトーム組成物。 1. A reconstituted lyophilized mesenchymal stem cell (MSC) secretome composition reconstituted from a lyophilized and/or lyophilized mesenchymal stem cell (MSC) secretome composition for use in treating an ocular condition in a subject in need thereof, wherein the lyophilized and/or lyophilized MSC secretome composition is a stable mesenchymal stem cell (MSC) secretome formulation, the stable mesenchymal stem cell (MSC) secretome formulation comprising:
i. 2 μg-20 μg of MSC secretome per mL;
ii. 2 mg to 3 mg per mL of sodium phosphate monobasic;
iii. 11 mg to 12 mg per mL of dibasic sodium phosphate;
iv. 11.5 mg to 13 mg of mannitol per mL;
v. 23 mg to 24 mg of trehalose dihydrate;
vi. 0.5 mg to 2 mg of optional hypromellose per mL;
The pH is from about 4.7 to about 7.5;
Reconstituted lyophilized MSC secretome composition .
ｉ．０．００４％～０．０８％ｗ／ｗのＭＳＣセクレトームと、
ｉｉ．４％～５％ｗ／ｗの一塩基性リン酸ナトリウムと、
ｉｉｉ．２１．５％～２３％ｗ／ｗの二塩基性リン酸ナトリウムと、
ｉｖ．２３％～２５％ｗ／ｗのマンニトールと、
ｖ．４６％～４８％ｗ／ｗのトレハロース脱水と、
ｖｉ．１％～３％ｗ／ｗの任意選択のヒプロメロースと、を含み、
ｐＨは約４．７～約７．５である、
再構成凍結乾燥ＭＳＣセクレトーム組成物。 1. A reconstituted lyophilized mesenchymal stem cell (MSC) secretome composition reconstituted from a lyophilized and/or lyophilized mesenchymal stem cell (MSC) secretome composition for use in treating an ocular condition in a subject in need thereof, wherein the lyophilized and/or lyophilized MSC secretome composition is a stable mesenchymal stem cell (MSC) secretome formulation, the stable mesenchymal stem cell (MSC) secretome formulation comprising:
i. 0.004%-0.08% w/w MSC secretome;
ii. 4% to 5% w/w of sodium phosphate monobasic;
iii. 21.5% to 23% w/w of dibasic sodium phosphate;
iv. 23% to 25% w/w mannitol;
v. 46% to 48% w/w trehalose dehydrate;
vi. 1% to 3% w/w of optional hypromellose;
The pH is from about 4.7 to about 7.5;
Reconstituted lyophilized MSC secretome composition .
ａ）抗酸化賦形剤が、アスコルビン酸、クエン酸、アセチルシステイン、システイン、メチオニン、亜硫酸塩（亜硫酸水素塩、メタ重亜硫酸塩）、モノチオグリセロール、グルタチオン、トコフェロールアルファ、及び没食子酸プロピルからなる群から選択される；および／または
ｂ）抗酸化賦形剤が、配合時及び／または凍結乾燥前に前記ＭＳＣセクレトーム組成物に添加される；および／または
ｃ）凍結乾燥組成物が、前記ＭＳＣセクレトーム組成物を瞬間凍結（－８０℃で実施）または凍結し、前記ＭＳＣセクレトーム組成物を凍結乾燥することによって得られる；および／または
ｄ）凍結乾燥後の前記ＭＳＣセクレトーム組成物中に、凍結乾燥前の前記ＭＳＣセクレトーム組成物中の因子の少なくとも７０％、少なくとも７５％、少なくとも８０％、少なくとも８５％、または少なくとも９０％が存在する；および／または
ｅ）凍結乾燥後の前記ＭＳＣセクレトーム組成物が、凍結乾燥前の前記ＭＳＣセクレトーム組成物と比較して少なくとも７０％、少なくとも７５％、少なくとも８０％、少なくとも８５％、または少なくとも９０％の生物活性を示す。 A freeze-dried and/or freeze-dried MSC secretome composition according to any one of claims 1 to 6 or a reconstituted freeze-dried MSC secretome composition according to any one of claims 9 to 11, wherein the freeze-dried and/or freeze-dried MSC secretome composition further comprises an antioxidant excipient; optionally
a) the antioxidant excipient is selected from the group consisting of ascorbic acid, citric acid, acetylcysteine, cysteine, methionine, sulfites (bisulfite, metabisulfite), monothioglycerol, glutathione, tocopherol alpha, and propyl gallate; and/or
b) an antioxidant excipient is added to the MSC secretome composition during formulation and/or prior to lyophilization; and/or
c) a lyophilized composition is obtained by flash freezing (performed at −80° C.) or freezing said MSC secretome composition and lyophilizing said MSC secretome composition; and/or
d) at least 70%, at least 75%, at least 80%, at least 85%, or at least 90% of the factors in the MSC secretome composition before freeze-drying are present in the MSC secretome composition after freeze-drying; and/or
e) the MSC secretome composition after lyophilization exhibits at least 70%, at least 75%, at least 80%, at least 85%, or at least 90% of the biological activity of the MSC secretome composition before lyophilization.
（ｉ）ａ）角膜細胞の層を提供するステップと、
ｂ）前記角膜細胞の層に創傷ギャップを導入するステップと、
ｃ）前記凍結乾燥組成物の存在下で前記創傷ギャップが治癒するかどうかを決定するステップであって、ステップｂ）の前または後のいずれかに前記凍結乾燥組成物を前記角膜細胞に投与する、前記決定するステップと、
を含むスクラッチアッセイであって、
前記凍結乾燥組成物が眼の創傷治癒を誘導することができ、前記眼の創傷治癒が、前記スクラッチアッセイにおける前記創傷ギャップの閉鎖によって示される前記スクラッチアッセイ、ならびに
（ｉｉ）ａ）多孔質膜を含むチャンバーに角膜細胞を添加するステップであって、前記組成物が存在しない基本培地を前記角膜細胞に補給する、前記添加するステップと、
ｂ）前記組成物が存在する前記基本培地を含む容器内に前記チャンバーを設置するステップであって、前記多孔質膜によって前記容器内の前記組成物から前記チャンバー内の前記角膜細胞が隔てられる、前記設置するステップと、
ｃ）前記角膜細胞を約１８～２４時間インキュベートするステップと、
ｄ）前記多孔質膜を介して遊走及び／または増殖した前記角膜細胞を測定するステップと、
を含むトランスウェル遊走アッセイであって、
前記凍結乾燥組成物が細胞遊走／増殖を誘導することができ、前記細胞遊走／増殖が、前記多孔質膜を介する前記角膜細胞の遊走及び／または増殖を誘導する前記組成物の能力によって示される前記トランスウェル遊走アッセイ、
からなる群から選択され；要すれば、前記凍結乾燥組成物が凍結乾燥ＭＳＣセクレトームであり；および／または
組成物が、少なくとも約４５μｇ／ｍｌ、少なくとも約５０μｇ／ｍｌ、または少なくとも約５５μｇ／ｍｌのタンパク質を含む、凍結乾燥組成物。 A lyophilized composition selected by or obtained from an assay, said assay comprising:
(i) a) providing a layer of corneal cells;
b) introducing a wound gap into said layer of corneal cells;
c) determining whether the wound gap heals in the presence of the lyophilized composition, wherein the lyophilized composition is administered to the corneal cells either before or after step b);
A scratch assay comprising:
a scratch assay, wherein the freeze-dried composition is capable of inducing ocular wound healing, the ocular wound healing being indicated by closure of the wound gap in the scratch assay; and (ii) a) adding corneal cells to a chamber comprising a porous membrane, the corneal cells being supplemented with a basal medium absent the composition;
b) placing the chamber in a container containing the basal medium in which the composition resides, the porous membrane separating the corneal cells in the chamber from the composition in the container;
c) incubating the corneal cells for about 18-24 hours;
d) measuring the corneal cells that have migrated and/or proliferated through the porous membrane;
A transwell migration assay comprising:
the transwell migration assay, wherein the lyophilized composition is capable of inducing cell migration/proliferation, the cell migration/proliferation being demonstrated by the ability of the composition to induce migration and/or proliferation of the corneal cells through the porous membrane;
optionally, the lyophilized composition is a lyophilized MSC secretome; and/or
A lyophilized composition , wherein the composition comprises at least about 45 μg/ml, at least about 50 μg/ml, or at least about 55 μg/ml of protein .
ａ）角膜細胞の層を提供することと、
ｂ）前記角膜細胞の層に創傷ギャップを導入することと、
ｃ）前記組成物の存在下で前記創傷ギャップが治癒するかどうかを決定することであって、ステップｂ）の前または後のいずれかに前記組成物を前記角膜細胞に投与する、前記決定することと、
を含み、
前記創傷ギャップの閉鎖が、眼の創傷治癒を誘導する能力を前記組成物が有することを示す、前記方法。 1. A method for determining the ability of a composition to induce ocular wound healing or a method for screening compositions for inducing ocular wound healing, said method comprising:
a) providing a layer of corneal cells;
b) introducing a wound gap into said layer of corneal cells;
c) determining whether the wound gap heals in the presence of the composition, wherein the composition is administered to the corneal cells either before or after step b); and
Including,
The method, wherein closure of the wound gap indicates that the composition has the ability to induce ocular wound healing.
ａ）多孔質膜を含むチャンバーに角膜細胞を添加することであって、前記組成物が存在しない基本培地を前記角膜細胞に補給する、前記添加することと、
ｂ）前記組成物が存在する前記基本培地を含む容器内に前記チャンバーを設置することであって、前記多孔質膜によって前記容器内の前記組成物から前記チャンバー内の前記角膜細胞が隔てられる、前記設置することと、
ｃ）前記角膜細胞を約１８～２４時間インキュベートすることと、
ｄ）前記多孔質膜を介して遊走及び／または増殖した前記角膜細胞を測定することであって、前記遊走及び／または増殖が、前記角膜細胞の遊走及び／または増殖を誘導する能力を前記組成物が有することを示す、前記測定することと、
を含み、要すれば、前記組成物が、少なくとも約４５μｇ／ｍｌ、少なくとも約５０μｇ／ｍｌ、または少なくとも約５５μｇ／ｍｌのタンパク質を含む；および／または
前記組成物が凍結乾燥される；および／または
前記組成物が凍結乾燥ＭＳＣセクレトームである、前記方法。 1. A method for determining the ability of a composition to induce migration and/or proliferation of corneal cells, said method comprising:
a) adding corneal cells to a chamber containing a porous membrane, the corneal cells being supplemented with a basal medium absent the composition;
b) placing the chamber in a container containing the basal medium in which the composition resides, the porous membrane separating the corneal cells in the chamber from the composition in the container;
c) incubating the corneal cells for about 18 to 24 hours;
d) measuring the corneal cells that have migrated and/or proliferated through the porous membrane, wherein the migration and/or proliferation indicates that the composition has the ability to induce the migration and/or proliferation of the corneal cells; and
optionally, the composition comprises at least about 45 μg/ml, at least about 50 μg/ml, or at least about 55 μg/ml of protein; and/or
the composition is lyophilized; and/or
The method , wherein the composition is a lyophilized MSC secretome .
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| PCT/US2021/026059 WO2021207282A2 (en) | 2020-04-07 | 2021-04-06 | Lyophilized mesenchymal stem cell derived secretome and uses thereof |
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