Standardization of platelet releasate products for clinical applications in cell therapy: a mathematical approach

Agostini, Francesco; Polesel, Jerry; Battiston, Monica; Lombardi, Elisabetta; Zanolin, Stefania; Ponte, Alessandro Da; Astori, Giuseppe; Durante, Cristina; Mazzucato, M.

doi:10.1186/s12967-017-1210-z

Cited by 22 publications

(32 citation statements)

References 24 publications

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“…Different approaches such as (nano)filtration and ultraviolet irradiation are commonly used for pathogen inactivation (Tekkatte et al, 2011). Human blood derivatives also present high batch-to-batch variability, and pooling large numbers of individual samples is necessary (Agostini et al, 2017). Components most commonly employed in XF cell culture are platelet derivatives and serum/plasma derivatives (Table 2; Burnouf, Strunk, Koh, & Schallmoser, 2016;Karnieli et al, 2017;Tekkatte et al, 2011).…”

Section: Human Blood-derived Components Used In Xf Ec Culturementioning

confidence: 99%

Fetal bovine serum-free culture of endothelial progenitor cells-progress and challenges

Bauman

Granja

Barrias

2018

J Tissue Eng Regen Med

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Two decades after the first report on endothelial progenitor cells (EPC), their key role in postnatal vasculogenesis and vascular repair is well established. The therapeutic potential of EPC and their growing use in clinical trials calls for the development of more robust, reproducible, and safer methods for the in vitro expansion and maintenance of these cells. Despite many limitations associated with its usage, fetal bovine serum (FBS) is still widely applied as a cell culture supplement. Although different approaches aiming at establishing FBS-free culture have been developed for many cell types, adequate solutions for endothelial cells, and for EPC in particular, are still scarce, possibly due to the multiple challenges that have to be faced when culturing these cells. In this review, we provide a brief overview on the therapeutic relevance of EPC and critically analyse the available literature on FBS-free endothelial cell culture methods, including xeno-free, serum-free, and chemically defined systems.

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Section: Human Blood-derived Components Used In Xf Ec Culturementioning

confidence: 99%

Fetal bovine serum-free culture of endothelial progenitor cells-progress and challenges

Bauman

Granja

Barrias

2018

J Tissue Eng Regen Med

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“…Interindividual differences between platelet donors and medium additive manufacturing methods [ 10 ] can strongly affect the capability to stimulate cell growth in vitro . Especially when dealing with small scale manufactured medium additives for academic purposes, quality controls are needed to assess the capacity of the ancillary product to stimulate cell proliferation in vitro [ 9 ]. In this paper we aimed to define a rapid and cost effective test to potentially predict the impact of a medium additive on cell growth rate: this represents a significant achievement, improving both production and quality control processes.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, results obtained by the luminescence based cell proliferation assay demonstrated that medium additives A (recalcified PRP) and B (recalcified PPP) induced a faster ASC growth rate, when compared to additives obtained by freeze and thaw approach. Considering the manufacturing process, medium additive A is extremely close to the product we previously named SRGF [ 2 , 9 ]. SRGF used in this work was obtained from different aliquots of human PRP.…”

Section: Discussionmentioning

confidence: 99%

“…Rapidly dividing mesenchymal stem cells are, in fact, known to be elongated and spindle shaped [ 5 , 6 ]. Interindividual differences between platelet donors could affect the capability to stimulate cell growth in vitro [ 7 , 8 ]: we demonstrated that, pooling together n = 16 SRGF products from single donors, standardized batches of medium additive can be obtained for applications in academic GMP facilities [ 4 , 9 ]. Nevertheless, we previously demonstrated that also the production method can affect medium additive capacity to stimulate cell growth in culture [ 10 ].Growth factors can, in fact, be extracted from platelets treating PRP by the so called freeze-and-thaw method [ 2 , 11 ], and we previously demonstrated that medium additives obtained by recalcification of PRP can promote a faster cell proliferation rate [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, we previously demonstrated that also the production method can affect medium additive capacity to stimulate cell growth in culture [ 10 ].Growth factors can, in fact, be extracted from platelets treating PRP by the so called freeze-and-thaw method [ 2 , 11 ], and we previously demonstrated that medium additives obtained by recalcification of PRP can promote a faster cell proliferation rate [ 10 ]. Especially when dealing with in-house manufactured medium additives, quality controls are needed also to assess and validate the capacity of the product to stimulate cell proliferation in vitro [ 9 ]. Direct evaluation of cell proliferation rate induced by different lots of medium additives is a long lasting test representing a significant workload in the production process.…”

Section: Introductionmentioning

confidence: 99%

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1H-NMR and MALDI-TOF MS as metabolomic quality control tests to classify platelet derived medium additives for GMP compliant cell expansion procedures

Agostini

Ruzza²,

Corpillo³

et al. 2018

PLoS ONE

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IntroductionEx vivo cell expansion under Good Manufacturing Practice (GMP) guidelines can be performed using medium additives containing human growth factors from platelets. These products can differently affect proliferation of adipose mesenchymal stromal stem cells (ASC). Qualification of medium additive performance is required for validation under GMP regulations: assessment of growth factor concentrations is not sufficient to predict the biological activity of the product batch. Proton nuclear magnetic resonance spectrometry (1H-NMR) and matrix-assisted laser desorption/ionization time of flight mass spectroscopy (MALDI-TOF MS) provide wide molecular characterization of samples.AimsWe aimed to assess if 1H-NMR and MALDI-TOF MS techniques can be used as quality control test potentially predicting the impact of a medium additive on cell proliferation.MethodsWe tested the impact on ASC growth rate (cell proliferation assessment and cell morphology analysis) of four medium additives, obtained by different methods from human platelet apheresis product. In order to classify each medium additive, we evaluated growth factor concentrations and spectra obtained by 1H-NMR and by MALDI-TOF MS.ResultsMedium additive obtained by CaCl2 activation of platelet rich products induced higher proliferation rate vs additive derived from platelet depleted ones. Additives obtained by freeze-and-thaw methods weakly induced ASC proliferation. As expected, principal component analysis of growth factor concentrations did not unravel specific biochemical features characterizing medium additives in relation with their biological activity. Otherwise, while 1H-NMR showed a partial resolution capacity, analysis of MALDI-TOF MS spectra allowed unambiguous distinction between the medium additives we used to differently stimulate cell growth in vitro.DiscussionMALDI-TOF and, despite limitations, 1H-NMR are promising cost effective and reliable quality controls to classify the potential of a medium additive to promote ASC growth. This can represent, after further investigations and appropriate validation, a significant advantage for GMP compliant manufacturing of advanced cell therapy products.

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The proteomic and particle composition of human platelet lysate for cell therapy products

Rodrigues

Valim

Berger

et al. 2022

J of Cellular Biochemistry

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Following health agencies warning, the use of animal origin supplements should be avoided in biological products proposed as therapy in humans.Platelet lysate and several other growth factors sources are alternatives to replace fetal calf serum, the current gold standard in clinical-grade cell culture. However, the platelet supplement's content lacks data due to different production methods. The principle behind these products relays on the lysis of platelets that release several proteins, some of which are contained in heterogeneous granules and coordinate biological functions. This study aims to analyze the composition and reproducibility of a platelet lysate produced with a standardized method, by describing several batches' protein and particle content using proteomics and dynamic light scattering. Proteomics data revealed a diversified protein content, with some related to essential cellular processes such as proliferation, morphogenesis, differentiation, biosynthesis, adhesion, and metabolism. It also detected proteins responsible for activation and binding of transforming growth factor beta, hepatocyte growth factor, and insulin-like growth factor. Total protein, biochemical, and growth factors quantitative data showed consistent and reproducible values across batches. Novel data on two major particle populations is presented, with high dispersion level at 231 ± 96 d.nm and at 30 ± 8 d.nm, possibly being an important way of protein trafficking through the cellular microenvironment. This experimental and descriptive analysis aims to support the content definition and quality criteria of a cell supplement for clinical applications.

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Standardization of platelet releasate products for clinical applications in cell therapy: a mathematical approach

Cited by 22 publications

References 24 publications

Fetal bovine serum-free culture of endothelial progenitor cells-progress and challenges

Fetal bovine serum-free culture of endothelial progenitor cells-progress and challenges

1H-NMR and MALDI-TOF MS as metabolomic quality control tests to classify platelet derived medium additives for GMP compliant cell expansion procedures

The proteomic and particle composition of human platelet lysate for cell therapy products

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