International Forum on GMP‐grade human platelet lysate for cell propagation

Strunk, Dirk; Lozano, Miguel; Marks, Denese C.; Loh, Yen Siew; Gstraunthaler, Gerhard; Schennach, Harald; Rohde, Eva; Laner-Plamberger, Sandra; Öller, Michaela; Nystedt, Johanna; Lotfi, Ramin; Rojewski, Markus; Schrezenmeier, Hubert; Schäfer, Richard; Bakchoul, Tamam; Waidmann, Marc; Jonsdottir-Buch, Sandra Mjoll; Montazeri, H.; Sigurjónsson, Ólafur E.; Iudicone, Paola; Fioravanti, Daniela; Pierelli, Luca; Introna, Martino; Capelli, Chiara; Falanga, Anna; Takanashi, Minoko; López-Villar, Olga; Burnouf, Thierry; Reems, Jo Anna; Pierce, Jan; Preslar, Amber; Schallmoser, Katharina

doi:10.1111/vox.12594

Cited by 16 publications

(21 citation statements)

References 39 publications

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“…The S/D treatment inactivates some bacteria and maintains the bactericidal activity of the complement . Finally, endotoxin and sterility testing of the final product can be performed . Therefore, countermeasures exist to mitigate risks of bacterial contamination of the source PC.…”

Section: Discussionmentioning

confidence: 99%

A double‐virally‐inactivated (Intercept–solvent/detergent) human platelet lysate for in vitro expansion of human mesenchymal stromal cells

Barro

Nebie

et al. 2019

Transfusion

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BACKGROUND: Pooled human platelet lysate (HPL) can replace fetal bovine serum (FBS) as xeno-free supplement for ex vivo expansion of mesenchymal stromal cells (MSCs). We evaluate here whether a double-virallyinactivated HPL (DVI-HPL) prepared from expired Intercepttreated platelet concentrates (PCs) and treated by solvent/detergent (S/D) can be used for MSC expansion.STUDY DESIGN AND METHODS: Expired Intercepttreated PCs in 65% platelet (PLT) additive solution were pooled and subjected to a 1% tri-n-butyl phosphate/1% Triton X-45 treatment followed by soybean oil, hydrophobic interaction chromatography purification, and sterile filtration. Bone marrow-derived MSCs (BM-MSCs) were expanded for four passages in growth medium containing 10% DVI-HPL, I-HPL (from Intercept-PC only), untreated HPL, and FBS. MSC morphology, doubling time, immunophenotype, immunosuppressive activity, and differentiation capacity were compared. RESULTS:Expanded cells had typical spindle morphology and showed higher viability in all HPL conditions than in FBS. The DVI-HPL and FBS-expanded cells were morphologically larger than in I-HPL and HPL supplements. The cumulative population doubling was lower using DVI-HPL than with HPL and I-HPL, but significantly higher than using FBS. Immunophenotype was not affected by the supplements used. Immunosuppressive activity was maintained with all supplements. Differentiation capacity into chondrocytes and osteocytes was more effective in DVI-HPL but less toward adipocytes compared to other supplements. CONCLUSIONS: Human PLT lysate made fromIntercept-PCs subjected to S/D treatment may be an alternative to untreated HPL and to I-HPL for BM-MSC expansion. This finding reinforces the potential of HPL as a virally safe alternative to FBS for clinical grade MSC expansion protocols. ABBREVIATIONS: BDNF = brain-derived neurotrophic factor; BM-MSC(s) = bone marrow-derived mesenchymal stromal cells; BrdU = bromodeoxyuridine/5-bromo-2 0 -deoxyuridine; CCK-8 = cell counting kit-8; DVI = double-virally-inactivated; DVI-HPL = doublevirally-inactivated (intercept-solvent/detergent) human platelet lysate; ECM = extracellular matrix; EGF = epidermal growth factor FBS = fetal bovine serum; HGF = hepatocyte growth factor HLA-DR = human leukocyte antigen DR; HPL = human platelet lysate; IGF = insulin-like growth factor-1; I-HPL = Intercept human platelet lysate; MSC(s) = mesenchymal stromal cells; PAS = platelet additive solution; PB19V = parvovirus B19; PC(s) = platelet concentrate(s); PD (s) = population doubling(s); PDGF-AB = platelet-derived growth factor-AB; PF4 = platelet factor 4; PHA = phytohemagglutinin; PPARG = peroxisome proliferator-activated receptor gamma; SOX9 = SRY (sex-determining region Y)-box 9; SPP1 = secreted phosphoprotein 1. From the

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Section: Discussionmentioning

confidence: 99%

A double‐virally‐inactivated (Intercept–solvent/detergent) human platelet lysate for in vitro expansion of human mesenchymal stromal cells

Barro

Nebie

et al. 2019

Transfusion

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“…In order to determine whether the duration of frozen storage of PCs affects the cytokine content of subsequently produced HPL, the storage times were divided into two categories: storage ≤ 4 months and > 4 months. Categorization was based on (a) recommendations regarding “quarantine storage” of GMP-grade blood products which state that the product must only be released if the donors have been tested negative for transmissible diseases twice, i.e., at the time of blood donation and re-tested as negative 4 months (or longer) thereafter [ 13 , 21 ], and (b) current practices at the HPL production site (Haukeland Hospital Bloodbank), which are in line with the above recommendations.…”

Section: Methodsmentioning

confidence: 99%

Influence of platelet storage time on human platelet lysates and platelet lysate-expanded mesenchymal stromal cells for bone tissue engineering

et al. 2020

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Background Human platelet lysate (HPL) is emerging as the preferred xeno-free supplement for the expansion of mesenchymal stromal cells (MSCs) for bone tissue engineering (BTE) applications. Due to a growing demand, the need for standardization and scaling-up of HPL has been highlighted. However, the optimal storage time of the source material, i.e., outdated platelet concentrates (PCs), remains to be determined. The present study aimed to determine the optimal storage time of PCs in terms of the cytokine content and biological efficacy of HPL. Methods Donor-matched bone marrow (BMSCs) and adipose-derived MSCs (ASCs) expanded in HPL or fetal bovine serum (FBS) were characterized based on in vitro proliferation, immunophenotype, and multi-lineage differentiation. Osteogenic differentiation was assessed at early (gene expression), intermediate [alkaline phosphatase (ALP) activity], and terminal stages (mineralization). Using a multiplex immunoassay, the cytokine contents of HPLs produced from PCs stored for 1–9 months were screened and a preliminary threshold of 4 months was identified. Next, HPLs were produced from PCs stored for controlled durations of 0, 1, 2, 3, and 4 months, and their efficacy was compared in terms of cytokine content and BMSCs’ proliferation and osteogenic differentiation. Results BMSCs and ASCs in both HPL and FBS demonstrated a characteristic immunophenotype and multi-lineage differentiation; osteogenic differentiation of BMSCs and ASCs was significantly enhanced in HPL vs. FBS. Multiplex network analysis of HPL revealed several interacting growth factors, chemokines, and inflammatory cytokines. Notably, stem cell growth factor (SCGF) was detected in high concentrations. A majority of cytokines were elevated in HPLs produced from PCs stored for ≤ 4 months vs. > 4 months. However, no further differences in PC storage times between 0 and 4 months were identified in terms of HPLs’ cytokine content or their effects on the proliferation, ALP activity, and mineralization of BMSCs from multiple donors. Conclusions MSCs expanded in HPL demonstrate enhanced osteogenic differentiation, albeit with considerable donor variation. HPLs produced from outdated PCs stored for up to 4 months efficiently supported the proliferation and osteogenic differentiation of MSCs. These findings may facilitate the standardization and scaling-up of HPL from outdated PCs for BTE applications.

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“…The "International Forum on GMP-grade human platelet lysate for cell propagation" provides good insight into the huge variability in production and quality testing. 3,4 The European Pharmacopeia general chapter on "Raw materials of biological origin for the production of cell-based and gene therapy medicinal products for human use" [Chapter 5.2.12]) sheds some light in this direction. It states that only carefully evaluated donors adequately tested for infectious transmissible agents according to EU and/or national regulation should be used.…”

Section: Qc and Standards For Releasementioning

confidence: 99%

“…hPL is routinely produced from PLT-rich plasma (PRP) or expired PLTs collected via apheresis. 3,4 Multiple freeze/thaw cycles cause the PLT membranes to burst and release trophogens and growth factors resulting in a lysate. Aggregates, debris, and PLT fragments are removed by centrifugation.…”

mentioning

confidence: 99%

“…Aggregates, debris, and PLT fragments are removed by centrifugation. 3,4 Human PLT lysate can be derived from autologous (same donor) collections, which may minimize the risk of immunologic reactions or infections; however, most efforts have focused on preparing allogeneic pooled batches from blood donations from a large number (50-100) of different individuals. The use of hPL in standard cell culture protocols could prove to be a promising tool for further development of cell therapy products in animal protein-free systems.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Gaps in the knowledge of human platelet lysate as a cell culture supplement for cell therapy: a joint publication from the AABB and the International Society for Cell & Gene Therapy

2019

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International Forum on GMP‐grade human platelet lysate for cell propagation

Cited by 16 publications

References 39 publications

A double‐virally‐inactivated (Intercept–solvent/detergent) human platelet lysate for in vitro expansion of human mesenchymal stromal cells

A double‐virally‐inactivated (Intercept–solvent/detergent) human platelet lysate for in vitro expansion of human mesenchymal stromal cells

Influence of platelet storage time on human platelet lysates and platelet lysate-expanded mesenchymal stromal cells for bone tissue engineering

Gaps in the knowledge of human platelet lysate as a cell culture supplement for cell therapy: a joint publication from the AABB and the International Society for Cell & Gene Therapy

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