Straum Olav K
Faculty of Humanities, Social Sciences, and Education, UiT The Arctic University of Norway, Tromsø, Norway.
PeerJ. 2020 Nov 13;8:e10303. doi: 10.7717/peerj.10303. eCollection 2020.
In the last decades, several in vitro studies have tested the effect of plate-rich plasma (PRP) on the proliferation of human cells in search of a wizard for the use of PRP in a clinical setting. However, the literature displays striking differences regarding this question despite the relatively similar experimental design. The aim of this review is twofold: describe and explain this diversity and suggest basic principles for further in vitro studies in the field. The optimal platelet concentration in vivo will also be discussed.
A search in mainly EMBASE and PubMed was performed to identify in vitro studies that investigate the effect of different PRP concentrations on human cell proliferation. The assessment of bias was based on the principles of "Good Cell Culture Practice" and adapted.
In total, 965 in vitro studies were detected. After the initial screening, 31 studies remained for full-text screening. A total of 16 studies met the criteria of final inclusion and appeared relatively sound. In general, the studies state consistently that PRP stimulates the proliferation of the human cell. Two main types of experimental techniques were detected: 1. using a fixed PRP concentration throughout the experiment, which leads to a substantial decrease in nutrition available at higher concentrations. 2. using a fixed PRP-to-media ratio (Vol/Vol) throughout the experiment. A general tendency was observed in both groups: when the PRP to media ratio increased (Vol/Vol), the proliferation rate decreased. Further, observed a substantial higher optimal PRP concentration than . No prominent tendencies was seen regarding anticoagulants, activation methods, and blood donor (age or sex).
Two major biases regarding optimal proliferation in vitro is pointed out: . It is speculated that the techniques used by some studies led to an adverse growth condition and even cell starvation at higher concentrations. Reduced proliferation rate due to proinflammatory substances released during degranulation of leukocytes.
The two main biases may explain the bell-shaped effect of PRP and the detrimental effects at higher platelet concentrations observed in several studies. These biases may also explain the low optimal PRP concentration observed in some studies. Even if one universal optimal PRP concentration does not exist, the review indicates that PRP concentrations in the upper parts of the scale is optimal or at least beneficial. Finally, following basic experimental principles are suggested. 1: The PRP/media ratio (Vol/Vol) should be kept as constant. 2: The PRP/media ratio should provide a sufficient nutrition supply, that is, PRP ≤ 10% (Vol/Vol). 3: The cell density per well (cells/mL) should be defined. 4: Leukocyte level should be kept low, preferable depleted (< 0.1 PLT/µL).
在过去几十年中，多项体外研究测试了富血小板血浆（PRP）对人类细胞增殖的影响，以寻找将PRP用于临床的有效方法。然而，尽管实验设计相对相似，但关于这个问题的文献显示出显著差异。本综述的目的有两个：描述和解释这种多样性，并为该领域的进一步体外研究提出基本原则。还将讨论体内的最佳血小板浓度。
主要在EMBASE和PubMed中进行检索，以识别研究不同PRP浓度对人类细胞增殖影响的体外研究。基于“良好细胞培养规范”的原则进行偏倚评估并进行调整。
总共检测到965项体外研究。初步筛选后，31项研究进入全文筛选。共有16项研究符合最终纳入标准且看起来相对可靠。总体而言，这些研究一致表明PRP能刺激人类细胞增殖。检测到两种主要的实验技术：1. 在整个实验中使用固定的PRP浓度，这会导致较高浓度下可用营养物质大幅减少。2. 在整个实验中使用固定的PRP与培养基比例（体积/体积）。两组均观察到一个普遍趋势：当PRP与培养基比例（体积/体积）增加时，增殖率下降。此外，[具体内容缺失]观察到的最佳PRP浓度明显高于[具体内容缺失]。在抗凝剂、激活方法和献血者（年龄或性别）方面未观察到明显趋势。
指出了关于体外最佳增殖的两个主要偏倚：[具体内容缺失]。据推测，一些研究使用的技术导致了不良的生长条件，甚至在较高浓度下细胞饥饿。由于白细胞脱颗粒过程中释放的促炎物质导致增殖率降低。
这两个主要偏倚可能解释了PRP的钟形效应以及多项研究中在较高血小板浓度下观察到的有害影响。这些偏倚也可能解释了一些研究中观察到的较低最佳PRP浓度。即使不存在一个通用的最佳PRP浓度，本综述表明，较高水平的PRP浓度是最佳的或至少是有益的。最后，建议遵循以下基本实验原则。1：PRP/培养基比例（体积/体积）应保持恒定。2：PRP/培养基比例应提供足够的营养供应，即PRP≤10%（体积/体积）。3：应定义每孔的细胞密度（细胞/毫升）。4：白细胞水平应保持较低，最好耗尽（<0.1血小板/微升）。
