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

被引:229
作者
Fekete, Natalie [1 ,2 ]
Gadelorge, Melanie [3 ]
Fuerst, Daniel [1 ,2 ]
Maurer, Caroline [1 ,2 ]
Dausend, Julia [1 ,2 ]
Fleury-Cappellesso, Sandrine [3 ]
Mailaender, Volker [1 ,2 ]
Lotfi, Ramin [1 ,2 ]
Ignatius, Anita
Sensebe, Luc [3 ]
Bourin, Philippe [3 ]
Schrezenmeier, Hubert [1 ,2 ]
Rojewski, Markus Thomas [1 ,2 ]
机构
[1] Univ Ulm, Inst Transfus Med, D-89081 Ulm, Germany
[2] DRK Blutspendedienst Baden Wurttemberg Hessen, Inst Klin Transfus Med & Immungenet Ulm, Ulm, Germany
[3] Etab Francais Sang Pyrenees Mediterranee Toulouse, Lab Therapie Cellulaire, Toulouse, France
关键词
blood platelets; chemokines; cytokines; mesenchymal progenitor cells; mesenchymal stromal cells; VERSUS-HOST-DISEASE; FETAL BOVINE SERUM; STEM-CELLS; CALF SERUM; UMBILICAL-CORD; RECEPTOR-BETA; ANIMAL SERUM; RICH PLASMA; GROWTH; MIGRATION;
D O I
10.3109/14653249.2012.655420
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Background aims. The clinical use of human mesenchymal stromal cells (MSC) requires ex vivo expansion in media containing supplements such as fetal bovine serum or, alternatively, human platelet lysate (PL). Methods. Platelet concentrates were frozen, quarantine stored, thawed and sterile filtered to obtain PL. PL content and its effect on fibroblast-colony-forming unit (CFU-F) formation, MSC proliferation and large-scale expansion were studied. Results. PL contained high levels of basic fibroblast growth factor (bFGF), soluble CD40L (sCD40L), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), platelet-derived growth factor AA (PDGF-AA), platelet-derived growth factor AB/BB (PDGF-AB/BB), chemokine (C-C) ligand 5 (CCL5; RANTES) transforming growth factor-beta 1 (TGF-beta 1) and chemokine (C-X-C) ligand 1/2/3 (GRO), with low batch-to-batch variability, and most were stable for up to 14 days. Inhibition of PDGF-BB and bFGF decreased MSC proliferation by about 20% and 50%, respectively. The strongest inhibition (about 75%) was observed with a combination of anti-bFGF + anti-PDGF-BB and anti-bFGF + anti-TGF-beta 1 + anti-PDGF-BB. Interestingly, various combinations of recombinant PDGF-BB, bFGF and TGF-beta 1 were not sufficient to promote cell proliferation. PL from whole blood-derived pooled platelet concentrates and apheresis platelet concentrates did not differ significantly in their growth-promoting activity on MSC. Conclusions. PL enhances MSC proliferation and can be regarded as a safe tool for MSC expansion for clinical purposes. \in particular, PDGF-BB and bFGF are essential components for the growth-promoting effect of PL, but are not sufficient for MSC proliferation.
引用
收藏
页码:540 / 554
页数:15
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