Abstract
Background aimsThe 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).MethodsPlatelet 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.ResultsPL 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-β1 (TGF-β1) 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-β1 + anti-PDGF-BB. Interestingly, various combinations of recombinant PDGF-BB, bFGF and TGF-β1 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.ConclusionsPL 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.
Highlights
The versatile application of mesenchymal stromal cells (MSC) for a diverse range of clinical indications has generated increasing interest in MSC as potential therapeutic agents in recent years
By carrying out neutralization experiments, we identified the factors that are essential for the stimulating activity on MSC proliferation
Pooled PC (PPC) were released for clinical-grade platelet lysate (PL) production only if all four donors contributing to a PPC had tested negative again after an interval of at least 4 months for the following infectious disease markers: human immunodeficiency virus (HIV) [by polymerase chain reaction (PCR) and serologic testing]; hepatitis C virus (HCV), hepatitis B (HBV) (by PCR, hepatitis B surface antigen (HBsAg) and anti-hepatitis B core protein), hepatitis A (HAV), parvovirus B19 and Treponema pallidum
Summary
The versatile application of mesenchymal stromal cells (MSC) for a diverse range of clinical indications has generated increasing interest in MSC as potential therapeutic agents in recent years. Extensive ex vivo expansion is required to obtain clinical doses [1] for cell therapy. 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). PL content and its effect on fibroblast–colony-forming unit (CFU-F) formation, MSC proliferation and large-scale expansion were studied. Inhibition of PDGF-BB and bFGF decreased MSC proliferation by about 20% and 50%, respectively. Various combinations of recombinant PDGF-BB, bFGF and TGF-β1 were not sufficient to promote cell proliferation. 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 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
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