全血由来血小板濃厚液から調製した血小板溶解液の間葉系幹細胞増幅培養における有用性

Platelet lysate（PL）は，fetal bovine serum（FBS）に代わるmesenchymal stem cell（MSC）の増幅培養の培地添加物として期待されている．PLの材料として，血小板通過型白血球除去（白除）フィルターによる白除全血から調製したwhole blood-derived platelet concentrate（WB-PC）を用いた．そのWB-PCから調製したPL（WB-PL）のMSC増幅培養における有用性を，apheresis PC（Aph-PC）から調製したPL（Aph-PL）と比較した．MSCの増殖に係る成長因子の濃度は，WB-PLとAph-P...

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Published in日本輸血細胞治療学会誌 Vol. 70; no. 6; pp. 597 - 606
Main Authors 紀野, 修一, 内藤, 祐, 生田, 克哉, 鳥本, 悦宏, 藤原, 満博, 秋野, 光明, 布施, 久恵, 加藤, 志歩, 若本, 志乃舞
Format Journal Article
LanguageJapanese
Published 一般社団法人 日本輸血・細胞治療学会 20.12.2024
日本輸血・細胞治療学会
Subjects
全血
血小板溶解液
血小板通過型白血球除去フィルター
間葉系幹細胞
Online AccessGet full text
ISSN1881-3011
1883-0625
DOI10.3925/jjtc.70.597

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Abstract Platelet lysate（PL）は，fetal bovine serum（FBS）に代わるmesenchymal stem cell（MSC）の増幅培養の培地添加物として期待されている．PLの材料として，血小板通過型白血球除去（白除）フィルターによる白除全血から調製したwhole blood-derived platelet concentrate（WB-PC）を用いた．そのWB-PCから調製したPL（WB-PL）のMSC増幅培養における有用性を，apheresis PC（Aph-PC）から調製したPL（Aph-PL）と比較した．MSCの増殖に係る成長因子の濃度は，WB-PLとAph-PLで同等であった．WB-PLのMSC増殖促進作用は，Aph-PLに比べると有意に弱かったがその差は僅かであり，FBSに比べて有意に強かった．WB-PLまたはAph-PLで培養したMSCは，MSCに特徴的な膜抗原発現パターンと脂肪細胞，骨芽細胞，軟骨細胞への3系統の分化能を維持していた．以上の結果より，WB-PLは，MSC増幅培養においてAph-PLの代替となる可能性が示唆された．
AbstractList Platelet lysate（PL）は，fetal bovine serum（FBS）に代わるmesenchymal stem cell（MSC）の増幅培養の培地添加物として期待されている．PLの材料として，血小板通過型白血球除去（白除）フィルターによる白除全血から調製したwhole blood-derived platelet concentrate（WB-PC）を用いた．そのWB-PCから調製したPL（WB-PL）のMSC増幅培養における有用性を，apheresis PC（Aph-PC）から調製したPL（Aph-PL）と比較した．MSCの増殖に係る成長因子の濃度は，WB-PLとAph-PLで同等であった．WB-PLのMSC増殖促進作用は，Aph-PLに比べると有意に弱かったがその差は僅かであり，FBSに比べて有意に強かった．WB-PLまたはAph-PLで培養したMSCは，MSCに特徴的な膜抗原発現パターンと脂肪細胞，骨芽細胞，軟骨細胞への3系統の分化能を維持していた．以上の結果より，WB-PLは，MSC増幅培養においてAph-PLの代替となる可能性が示唆された．
Platelet lysate(PL)は, fetal bovine serum(FBS)に代わるmesenchymal stem cell(MSC)の増幅培養の培地添加物として期待されている. PLの材料として, 血小板通過型白血球除去(白除)フィルターによる白除全血から調製したwhole blood-derived platelet concentrate(WB-PC)を用いた. そのWB-PCから調製したPL(WB-PL)のMSC増幅培養における有用性を, apheresis PC(Aph-PC)から調製したPL(Aph-PL)と比較した. MSCの増殖に係る成長因子の濃度は, WB-PLとAph-PLで同等であった. WB-PLのMSC増殖促進作用は, Aph-PLに比べると有意に弱かったがその差は僅かであり, FBSに比べて有意に強かった. WB-PLまたはAph-PLで培養したMSCは, MSCに特徴的な膜抗原発現パターンと脂肪細胞, 骨芽細胞, 軟骨細胞への3系統の分化能を維持していた. 以上の結果より, WB-PLは, MSC増幅培養においてAph-PLの代替となる可能性が示唆された.
Author 藤原, 満博
若本, 志乃舞
生田, 克哉
加藤, 志歩
布施, 久恵
秋野, 光明
鳥本, 悦宏
内藤, 祐
紀野, 修一
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References 15) Capelli C, Domenghini M, Borleri G, et al: Human platelet lysate allows expansion and clinical grade production of mesenchymal stromal cells from small samples of bone marrow aspirates or marrow filter washouts. Bone Marrow Transplant, 40: 785-791, 2007.
22) Fekete N, Gadelorge M, Fürst D, et al: Platelet lysate from whole blood-derived pooled platelet concentrates and apheresis-derived platelet concentrates for the isolation and expansion of human bone marrow mesenchymal stromal cells: production process, content and identification of active components. Cytotherapy, 14: 540-554, 2012.
20) González MB, Cuerva RC, Muñoz BF, et al: Optimization of human platelet lysate production and pathogen reduction in a public blood transfusion center. Transfusion, 62: 1839-1849, 2022.
32) Strandberg G, Sellberg F, Sommar P, et al: Standardizing the freeze-thaw preparation of growth factors from platelet lysate. Transfusion, 57: 1058-1065, 2017.
24) Notodihardjo SC, Morimoto N, Kakudo N, et al: Comparison of the efficacy of cryopreserved human platelet lysate and refrigerated lyophilized human platelet lysate for wound healing. Regenerative Therapy, 10: 1-9, 2019.
33) Viau S, Chabrand L, Eap S, et al: Pathogen reduction through additive-free short-wave UV light irradiation retains the optimal efficacy of human platelet lysate for the expansion of human bone marrow mesenchymal stem cells. PLoS One, 12: e0181406, 2017.
1) Pittenger MF, Mackay AM, Beck SC, et al: Multilineage potential of adult human mesenchymal stem cells. Science, 284: 143-147, 1999.
35) Viau S, Eap S, Chabrand L, et al: Viral inactivation of human platelet lysate by gamma irradiation preserves its optimal efficiency in the expansion of human bone marrow mesenchymal stromal cells. Transfusion, 59: 1069-1079, 2019.
31) Strunk D, Lozano M, Marks DC, et al: International Forum on GMP-grade human platelet lysate for cell propagation: summary. Vox Sang, 113: 80-87, 2018.
12) Carrancio S, López-Holgado N, Sánchez-Guijo FM, et al: Optimization of mesenchymal stem cell expansion procedures by cell separation and culture conditions modification. Exp Hematol, 36: 1014-1021, 2008.
27) Paunovic D, van der Meer P, Kjeldsen-Kragh J, et al: Multicenter evaluation of a whole-blood filter that saves platelets. Transfusion, 44: 1197-1203, 2004.
37) Bui HTH, Nguyen LT, Than UTT: Influences of xeno-free media on mesenchymal stem cell expansion for clinical application. Tissue Eng Regen Med, 18: 15-23, 2021.
14) Mojica-Henshaw MP, Jacobson P, Morris J, et al: Serum-converted platelet lysate can substitute for fetal bovine serum in human mesenchymal stromal cell cultures. Cytotherapy, 15: 1458-1468, 2013.
3) Even MS, Sandusky CB, Barnard ND: Serum-free hybridoma culture: ethical, scientific and safety considerations. Trends Biotechnol, 24: 105-108, 2006.
23) Tan C, Shichinohe H, Wang Z, et al: Feasibility and efficiency of human bone marrow stromal cell culture with allogeneic platelet lysate-supplementation for cell therapy against stroke. Stem Cells Int, 2016: 6104780, 2016.
13) Pérez-Ilzarbe M, Díez-Campelo M, Aranda P, et al: Comparison of ex vivo expansion culture conditions of mesenchymal stem cells for human cell therapy. Transfusion, 49: 1901-1910, 2009.
36) Cimino M, Gonçalves RM, Barrias CC, et al: Xeno-free strategies for safe human mesenchymal stem/stromal cell expansion: Supplements and coatings. Stem Cells Int, 2017: 6597815, 2017.
17) Schallmoser K, Bartmann C, Rohde E, et al: Human platelet lysate can replace fetal bovine serum for clinical-scale expansion of functional mesenchymal stromal cells. Transfusion, 47: 1436-1446, 2007.
26) Shichinohe H, Kawabori M, Iijima H, et al: Research on advanced intervention using novel bone marrOW stem cell (RAINBOW): a study protocol for a phase I, open-label, uncontrolled, dose-response trial of autologous bone marrow stromal cell transplantation in patients with acute ischemic stroke. BMC Neurol, 17: 179, 2017.
18) Bieback K, Hecker A, Kocaömer A, et al: Human alternatives to fetal bovine serum for the expansion of mesenchymal stromal cells from bone marrow. Stem Cells, 27: 2331-2341, 2009.
5) Burnouf T, Strunk D, Koh MBC, et al: Human platelet lysate: replacing fetal bovine serum as a gold standard for human cell propagation? Biomaterials, 76: 371-387, 2016.
8) Introna M, Lucchini G, Dander E, et al: Treatment of graft versus host disease with mesenchymal stromal cells: a phase I study on 40 adult and pediatric patients. Biol Blood Marrow Transplant, 20: 375-381, 2014.
21) Palombella S, Perucca Orfei C, Castellini G, et al: Systematic review and meta-analysis on the use of human platelet lysate for mesenchymal stem cell cultures: comparison with fetal bovine serum and considerations on the production protocol. Stem Cell Res & Ther, 13: 142, 2022.
28) Snyder EL, Whitley P, Kingsbury T, et al: In vitro and in vivo evaluation of a whole blood platelet-sparing leukoreduction filtration system. Transfusion, 50: 2145-2151, 2010.
6) Doucet C, Ernou I, Zhang Y, et al: Platelet lysates promote mesenchymal stem cell expansion: A safety substitute for animal serum in cell-based therapy applications. J Cell Physiol, 205: 228-236, 2005.
9) Sánchez-Guijo F, Caballero-Velázquez T, López-Villar O, et al: Sequential third-party mesenchymal stromal cell therapy for refractory acute graft-versus-host disease. Biol Blood Marrow Transplant, 20: 1580-1585, 2014.
7) von Bonin M, Stölzel F, Goedecke A, et al: Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant, 43: 245-251, 2009.
2) Dominici M, Le Blanc K, Mueller I, et al: Minimal criteria for defining multipotent mesenchymal stromal cells. The international Society for Cellular Therapy position statement. Cytotherapy, 8: 315-317, 2006.
11) Bernardo ME, Avanzini MA, Perotti C, et al: Optimization of in vitro expansion of human multipotent mesenchymal stromal cells for cell-therapy approaches: further insights in the search for a fetal calf serum substitute. J Cell Physiol, 211: 121-130, 2007.
16) Lange C, Cakiroglu F, Spiess AN, et al: Accelerated and safe expansion of human mesenchymal stromal cells in animal serum-free medium for transplantation and regenerative medicine. J Cell Physiol, 213: 18-26, 2007.
10) Gjerde C, Mustafa K, Hellem S, et al: Cell therapy induced regeneration of severely atrophied mandibular bone in a clinical trial. Stem Cell Res Ther, 9: 213, 2018.
29) Cavagnetto C, Alejo Blanco R, McKenna H, et al: Residual red cells in blood components: A multisite study of fully automated enumeration using a hematology analyzer. Transfusion, 61: 568-578, 2021.
19) Guiotto M, Raffoul W, Hart AM, et al: Human platelet lysate to substitute fetal bovine serum in hMSC expansion for translational applications: a systematic review. J Transl Med, 15: 351, 2020.
25) 若本志乃舞, 藤原満博, 名村喜一郎, 他: 再生医療・細胞治療で使用される細胞の増幅に添加する血小板溶解液 (Platelet lysate) の調製方法と評価の検討. 血液事業, 42: 98-99, 2019.
30) Kuznetsov SA, Friedenstein AJ, Robey PG: Factors required for bone marrow stromal fibroblast colony formation in vitro. Br J Haematol, 97: 561-570, 1997.
4) Hemeda H, Giebel B, Wagner W: Evaluation of human platelet lysate versus fetal bovine serum for culture of mesenchymal stromal cells. Cytotherapy, 16: 170-180, 2014.
34) Barro L, Su Y-T, Nebie O, et al: A double-virally-inactivated (intercept-solvent/detergent) human platelet lysate for in vitro expansion of human mesenchymal stromal cells. Transfusion, 59: 2061-2073, 2019.
References_xml – reference: 11) Bernardo ME, Avanzini MA, Perotti C, et al: Optimization of in vitro expansion of human multipotent mesenchymal stromal cells for cell-therapy approaches: further insights in the search for a fetal calf serum substitute. J Cell Physiol, 211: 121-130, 2007.
– reference: 20) González MB, Cuerva RC, Muñoz BF, et al: Optimization of human platelet lysate production and pathogen reduction in a public blood transfusion center. Transfusion, 62: 1839-1849, 2022.
– reference: 6) Doucet C, Ernou I, Zhang Y, et al: Platelet lysates promote mesenchymal stem cell expansion: A safety substitute for animal serum in cell-based therapy applications. J Cell Physiol, 205: 228-236, 2005.
– reference: 23) Tan C, Shichinohe H, Wang Z, et al: Feasibility and efficiency of human bone marrow stromal cell culture with allogeneic platelet lysate-supplementation for cell therapy against stroke. Stem Cells Int, 2016: 6104780, 2016.
– reference: 24) Notodihardjo SC, Morimoto N, Kakudo N, et al: Comparison of the efficacy of cryopreserved human platelet lysate and refrigerated lyophilized human platelet lysate for wound healing. Regenerative Therapy, 10: 1-9, 2019.
– reference: 25) 若本志乃舞, 藤原満博, 名村喜一郎, 他: 再生医療・細胞治療で使用される細胞の増幅に添加する血小板溶解液 (Platelet lysate) の調製方法と評価の検討. 血液事業, 42: 98-99, 2019.
– reference: 29) Cavagnetto C, Alejo Blanco R, McKenna H, et al: Residual red cells in blood components: A multisite study of fully automated enumeration using a hematology analyzer. Transfusion, 61: 568-578, 2021.
– reference: 10) Gjerde C, Mustafa K, Hellem S, et al: Cell therapy induced regeneration of severely atrophied mandibular bone in a clinical trial. Stem Cell Res Ther, 9: 213, 2018.
– reference: 14) Mojica-Henshaw MP, Jacobson P, Morris J, et al: Serum-converted platelet lysate can substitute for fetal bovine serum in human mesenchymal stromal cell cultures. Cytotherapy, 15: 1458-1468, 2013.
– reference: 18) Bieback K, Hecker A, Kocaömer A, et al: Human alternatives to fetal bovine serum for the expansion of mesenchymal stromal cells from bone marrow. Stem Cells, 27: 2331-2341, 2009.
– reference: 28) Snyder EL, Whitley P, Kingsbury T, et al: In vitro and in vivo evaluation of a whole blood platelet-sparing leukoreduction filtration system. Transfusion, 50: 2145-2151, 2010.
– reference: 37) Bui HTH, Nguyen LT, Than UTT: Influences of xeno-free media on mesenchymal stem cell expansion for clinical application. Tissue Eng Regen Med, 18: 15-23, 2021.
– reference: 33) Viau S, Chabrand L, Eap S, et al: Pathogen reduction through additive-free short-wave UV light irradiation retains the optimal efficacy of human platelet lysate for the expansion of human bone marrow mesenchymal stem cells. PLoS One, 12: e0181406, 2017.
– reference: 2) Dominici M, Le Blanc K, Mueller I, et al: Minimal criteria for defining multipotent mesenchymal stromal cells. The international Society for Cellular Therapy position statement. Cytotherapy, 8: 315-317, 2006.
– reference: 12) Carrancio S, López-Holgado N, Sánchez-Guijo FM, et al: Optimization of mesenchymal stem cell expansion procedures by cell separation and culture conditions modification. Exp Hematol, 36: 1014-1021, 2008.
– reference: 26) Shichinohe H, Kawabori M, Iijima H, et al: Research on advanced intervention using novel bone marrOW stem cell (RAINBOW): a study protocol for a phase I, open-label, uncontrolled, dose-response trial of autologous bone marrow stromal cell transplantation in patients with acute ischemic stroke. BMC Neurol, 17: 179, 2017.
– reference: 7) von Bonin M, Stölzel F, Goedecke A, et al: Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant, 43: 245-251, 2009.
– reference: 15) Capelli C, Domenghini M, Borleri G, et al: Human platelet lysate allows expansion and clinical grade production of mesenchymal stromal cells from small samples of bone marrow aspirates or marrow filter washouts. Bone Marrow Transplant, 40: 785-791, 2007.
– reference: 5) Burnouf T, Strunk D, Koh MBC, et al: Human platelet lysate: replacing fetal bovine serum as a gold standard for human cell propagation? Biomaterials, 76: 371-387, 2016.
– reference: 4) Hemeda H, Giebel B, Wagner W: Evaluation of human platelet lysate versus fetal bovine serum for culture of mesenchymal stromal cells. Cytotherapy, 16: 170-180, 2014.
– reference: 35) Viau S, Eap S, Chabrand L, et al: Viral inactivation of human platelet lysate by gamma irradiation preserves its optimal efficiency in the expansion of human bone marrow mesenchymal stromal cells. Transfusion, 59: 1069-1079, 2019.
– reference: 21) Palombella S, Perucca Orfei C, Castellini G, et al: Systematic review and meta-analysis on the use of human platelet lysate for mesenchymal stem cell cultures: comparison with fetal bovine serum and considerations on the production protocol. Stem Cell Res & Ther, 13: 142, 2022.
– reference: 31) Strunk D, Lozano M, Marks DC, et al: International Forum on GMP-grade human platelet lysate for cell propagation: summary. Vox Sang, 113: 80-87, 2018.
– reference: 13) Pérez-Ilzarbe M, Díez-Campelo M, Aranda P, et al: Comparison of ex vivo expansion culture conditions of mesenchymal stem cells for human cell therapy. Transfusion, 49: 1901-1910, 2009.
– reference: 3) Even MS, Sandusky CB, Barnard ND: Serum-free hybridoma culture: ethical, scientific and safety considerations. Trends Biotechnol, 24: 105-108, 2006.
– reference: 27) Paunovic D, van der Meer P, Kjeldsen-Kragh J, et al: Multicenter evaluation of a whole-blood filter that saves platelets. Transfusion, 44: 1197-1203, 2004.
– reference: 32) Strandberg G, Sellberg F, Sommar P, et al: Standardizing the freeze-thaw preparation of growth factors from platelet lysate. Transfusion, 57: 1058-1065, 2017.
– reference: 9) Sánchez-Guijo F, Caballero-Velázquez T, López-Villar O, et al: Sequential third-party mesenchymal stromal cell therapy for refractory acute graft-versus-host disease. Biol Blood Marrow Transplant, 20: 1580-1585, 2014.
– reference: 36) Cimino M, Gonçalves RM, Barrias CC, et al: Xeno-free strategies for safe human mesenchymal stem/stromal cell expansion: Supplements and coatings. Stem Cells Int, 2017: 6597815, 2017.
– reference: 16) Lange C, Cakiroglu F, Spiess AN, et al: Accelerated and safe expansion of human mesenchymal stromal cells in animal serum-free medium for transplantation and regenerative medicine. J Cell Physiol, 213: 18-26, 2007.
– reference: 1) Pittenger MF, Mackay AM, Beck SC, et al: Multilineage potential of adult human mesenchymal stem cells. Science, 284: 143-147, 1999.
– reference: 8) Introna M, Lucchini G, Dander E, et al: Treatment of graft versus host disease with mesenchymal stromal cells: a phase I study on 40 adult and pediatric patients. Biol Blood Marrow Transplant, 20: 375-381, 2014.
– reference: 17) Schallmoser K, Bartmann C, Rohde E, et al: Human platelet lysate can replace fetal bovine serum for clinical-scale expansion of functional mesenchymal stromal cells. Transfusion, 47: 1436-1446, 2007.
– reference: 22) Fekete N, Gadelorge M, Fürst D, et al: Platelet lysate from whole blood-derived pooled platelet concentrates and apheresis-derived platelet concentrates for the isolation and expansion of human bone marrow mesenchymal stromal cells: production process, content and identification of active components. Cytotherapy, 14: 540-554, 2012.
– reference: 30) Kuznetsov SA, Friedenstein AJ, Robey PG: Factors required for bone marrow stromal fibroblast colony formation in vitro. Br J Haematol, 97: 561-570, 1997.
– reference: 19) Guiotto M, Raffoul W, Hart AM, et al: Human platelet lysate to substitute fetal bovine serum in hMSC expansion for translational applications: a systematic review. J Transl Med, 15: 351, 2020.
– reference: 34) Barro L, Su Y-T, Nebie O, et al: A double-virally-inactivated (intercept-solvent/detergent) human platelet lysate for in vitro expansion of human mesenchymal stromal cells. Transfusion, 59: 2061-2073, 2019.
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Snippet Platelet lysate（PL）は，fetal bovine serum（FBS）に代わるmesenchymal stem cell（MSC）の増幅培養の培地添加物として期待されている．PLの材料として，血小板通過型白血球除去（白除）フィルターによる白除全血から調製したwhole blood-derived...
Platelet lysate(PL)は, fetal bovine serum(FBS)に代わるmesenchymal stem cell(MSC)の増幅培養の培地添加物として期待されている. PLの材料として, 血小板通過型白血球除去(白除)フィルターによる白除全血から調製したwhole...
SourceID medicalonline
jstage
SourceType Publisher
StartPage 597
SubjectTerms 全血
血小板溶解液
血小板通過型白血球除去フィルター
間葉系幹細胞
Title 全血由来血小板濃厚液から調製した血小板溶解液の間葉系幹細胞増幅培養における有用性
URI https://www.jstage.jst.go.jp/article/jjtc/70/6/70_597/_article/-char/ja
http://mol.medicalonline.jp/en/journal/download?GoodsID=cc5trcel/2024/007006/004&name=0597-0606j
Volume 70
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ispartofPNX 日本輸血細胞治療学会誌, 2024/12/20, Vol.70(6), pp.597-606
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