Gender and Age Differences in Growth Factor Concentrations From Platelet-Rich Plasma in Adults

Evanson, J. Richard; Guyton, M. Kelly; Oliver, David L.; Hire, Justin M.; Topolski, Richard; Zumbrun, Steven D.; McPherson, James C.; Bojescul, John A.

doi:10.7205/milmed-d-13-00336

Cited by 91 publications

(86 citation statements)

References 31 publications

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“…Batch‐to‐batch consistency in HPL batches seems to require the pooling of 40 to 50 PC donations, corresponding to approximately 250 donors when using “random‐donor” PCs. Pooling minimizes inherent donor‐to‐donor variability due to impact of age or sex, such as the content in growth factors and other cell growth–promoting molecules, which are important components for growth medium supplementation . However, pooling increases the risk of contamination by 1) window period donations, 2) viruses that are not tested for, or 3) emerging agents, making the implementation of virus/pathogen inactivation procedures required .…”

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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“…Further, estrogen and androgen facilitate angiogenesis through different mechanisms. Finally, females and males have different amounts of circulating pro-angiogenic and anti-angiogenic factors, which may further contribute to the sex differences in tumor angiogenesis epidermal growth factor (EGF), insulin growth factor-1 (IGF-1), PDGF-BB, and VEGF, were significantly higher in women [373]. Conversely, another study of plateletrich plasma found that PDGF-BB was higher in men and found no sex differences in IGF-1 levels [374].…”

Section: Sex Differences In Angiogenesismentioning

confidence: 99%

Sex differences in cancer mechanisms

et al. 2020

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We now know that cancer is many different diseases, with great variation even within a single histological subtype. With the current emphasis on developing personalized approaches to cancer treatment, it is astonishing that we have not yet systematically incorporated the biology of sex differences into our paradigms for laboratory and clinical cancer research. While some sex differences in cancer arise through the actions of circulating sex hormones, other sex differences are independent of estrogen, testosterone, or progesterone levels. Instead, these differences are the result of sexual differentiation, a process that involves genetic and epigenetic mechanisms, in addition to acute sex hormone actions. Sexual differentiation begins with fertilization and continues beyond menopause. It affects virtually every body system, resulting in marked sex differences in such areas as growth, lifespan, metabolism, and immunity, all of which can impact on cancer progression, treatment response, and survival. These organismal level differences have correlates at the cellular level, and thus, males and females can fundamentally differ in their protections and vulnerabilities to cancer, from cellular transformation through all stages of progression, spread, and response to treatment. Our goal in this review is to cover some of the robust sex differences that exist in core cancer pathways and to make the case for inclusion of sex as a biological variable in all laboratory and clinical cancer research. We finish with a discussion of lab-and clinic-based experimental design that should be used when testing whether sex matters and the appropriate statistical models to apply in data analysis for rigorous evaluations of potential sex effects. It is our goal to facilitate the evaluation of sex differences in cancer in order to improve outcomes for all patients.

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“…Such a relevant number of different preparation protocols should be taken into account whenever inconsistencies are found from comparing clinical outcomes reported in the literature [32]. The quality of PRP could be affected by patient's heterogeneity in terms of age, gender, body mass index, comorbidities, healing capabilities, and different lifestyles [33]. In order to reduce at least the protocol-dependent variability, the authors selected a closed preparation system, which, being automatic, limits the possibility of operator-dependent errors and reduces the risk of microbial contamination, while processing the blood.…”

Section: Introductionmentioning

confidence: 99%

Cytokine, chemokine, and growth factor profile of platelet-rich plasma

et al. 2016

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During wound healing, biologically active molecules are released from platelets. The rationale of using platelet-rich plasma (PRP) relies on the concentration of bioactive molecules and subsequent delivery to healing sites. These bioactive molecules have been seldom simultaneously quantified within the same PRP preparation. In the present study, the flexible Bio-Plex system was employed to assess the concentration of a large range of cytokines, chemokines, and growth factors in 16 healthy volunteers so as to determine whether significant baseline differences may be found. Besides IL-1b, IL-1ra, IL-4, IL-6, IL-8, IL-12, IL-13, IL-17, INF-γ, TNF-α, MCP-1, MIP-1a, RANTES, bFGF, PDGF, and VEGF that were already quantified elsewhere, the authors reported also on the presence of IL-2, IL-5, IL-7, IL-9, IL-10, IL-15 G-CSF, GM-CSF, Eotaxin, CXCL10 chemokine (IP-10), and MIP 1b. Among the most interesting results, it is convenient to mention the high concentrations of the HIV-suppressive and inflammatory cytokine RANTES and a statistically significant difference between males and females in the content of PDGF-BB. These data are consistent with previous reports pointing out that gender, diet, and test system affect the results of platelet function in healthy subjects, but seem contradictory when compared to other quantification assays in serum and plasma. The inconsistencies affecting the experimental results found in literature, along with the variability found in the content of bioactive molecules, urge further research, hopefully in form of randomized controlled clinical trials, in order to find definitive evidence of the efficacy of PRP treatment in various pathologic and regenerative conditions.

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Gender and Age Differences in Growth Factor Concentrations From Platelet-Rich Plasma in Adults

Cited by 91 publications

References 31 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

Sex differences in cancer mechanisms

Cytokine, chemokine, and growth factor profile of platelet-rich plasma

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