A Comparative Medicine Study of Platelet Biophysics Among Hemostasis Models of Different Species

止血 血小板 化学 生物物理学 血小板粘附 收缩(语法) 血小板活化 血栓 医学 生物 内科学 免疫学 血小板聚集
作者
Renee Copeland,Oluwamayokun Oshinowo,Yumiko Sakurai,Meredith E. Fay,Brian G. Petrich,Benjamin M. Brainard,Wilbur A. Lam,David R. Myers
出处
期刊:Blood [Elsevier BV]
卷期号:132 (Supplement 1): 869-869
标识
DOI:10.1182/blood-2018-99-113107
摘要

Abstract Background: Animal models of hemostasis play a crucial role in understanding hemostasis and developing novel therapeutic treatments. Hemostasis is a mechanical phenomenon and recent studies have demonstrated that biophysical parameters, such as platelet margination (Walton et al. Blood 2017), thrombus porosity (Welsh et al. Blood 2014), shear forces (Nesbitt et al. Nat Med 2009), compression forces (Ju et al. Nat Comm 2018), and single platelet forces, as measured by platelet contraction cytometry, developed by our laboratory, (Myers et al. Nat Mat. 2017) affect hemostatic processes and may be pathologically altered in disease states. However, little is known about the most basic biophysical interspecies differences between platelets of various animal hemostasis models, which could provide critical insight into interpreting data and results. Here, we report the results of our initial study on platelet biophysics in humans (n=5), mice (n=8), pigs (n=5), and dogs (n=6), which are commonly used for hemostasis models due to anatomical similarities to human vessels, organs, and cell function (Siller-Matula et al. Thromb & Haem 2008) (Jagadeeswaran et al. Circ Res 2015). We focus on understanding differences in platelet adhesion on collagen and fibrinogen, spreading area, singe cell contraction forces, and bulk contraction, which all may influence the initiation and stability of blood clots (Fig. 1). Our data demonstrates striking differences between each species, especially concerning adhesion, spreading area, and single platelet force. Surprisingly, measurements of volumetric bulk contraction, the most commonly used biophysical assay in hemostasis research, appear to be quite consistent between species. Methods: We performed a comprehensive study of platelet biophysics using adhesion assays, bulk contraction, and single platelet contractile forces on humans, mice, pigs, and dogs' platelets. For the adhesion assays, spreading area, and platelet contractile forces, platelets were gel-filtered as described previously (Myers et al. 2017). Cell Adhesion & Spreading Assay: Gel filtered platelets were diluted to 20M/mL, incubated on coverslips that had been incubated with type 1 collagen (100 µg/mL) or fibrinogen (100 µg/mL), allowed to adhere for 2 hours, counted, and measured. Platelet Contraction Cytometry: Polyacrylamide hydrogels with pairs of fibrinogen microdots are fabricated at physiologically relevant stiffnesses. Gel-filtered thrombin-activated platelets (1 U/mL) are then plated to attach, spread, and contract the microdots together. Individual platelet force is directly proportional to the microdot displacement measured with fluorescent imaging. Bulk Clot Contraction Assay: Platelets are washed as described previously (Lam et al. Nat Mat 2011) and then diluted to 200M/mL in a solution of fibrinogen (2 mg/mL), CaCl2 (5 mM), and thrombin (1 U/mL). Clots are left to form in cuvettes lined with gridded paper and measured every 30 mins for 2.5 hours. All assays were performed on at least 3 subjects from each species and in triplicate when possible. Results: We found both significant biophysical differences and similarities between platelets of different species (Fig. 2). Overall, murine platelets have the highest biophysical similarity to human platelets regarding adhesion, volumetric contraction, and single platelet contractile force despite substantial size differences. Porcine platelets exhibited enhanced adhesion on collagen with little adhesion to fibrinogen; while canine platelets showed the opposite. Such differences could have significant implications on the biophysical initiation of blood hemostasis and thrombosis, as well as the thrombogenicity tests of new materials. In bulk and single platelet contraction, we noted that similarities between most species except for canine platelets which produced forces nearly triple that of humans, the highest contractile forces of any platelets measured to date. As recent work has shown that forces are linked to clot porosity and therefore activation (Mirramezani et al. JTH 2018), such high forces could influence the clot hierarchical structure and subsequent lysis. Taken together, these results demonstrate how the biophysical properties of platelets differ across species and may be another reason why animal studies of hemostasis do not always translate to humans. Disclosures No relevant conflicts of interest to declare.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
量子星尘发布了新的文献求助10
刚刚
ROOKIE完成签到,获得积分10
1秒前
1秒前
阿胡发布了新的文献求助10
2秒前
2秒前
SYLH应助wodetaiyangLLL采纳,获得10
3秒前
loey完成签到,获得积分10
3秒前
等待的音响完成签到,获得积分10
3秒前
3秒前
孙非完成签到,获得积分10
3秒前
江小鱼在查文献完成签到,获得积分10
4秒前
静xixi完成签到,获得积分20
5秒前
就是躺完成签到 ,获得积分10
6秒前
6秒前
xcc完成签到,获得积分10
7秒前
目眩完成签到,获得积分10
7秒前
等待的花卷完成签到 ,获得积分10
8秒前
莫言发布了新的文献求助10
9秒前
潇潇完成签到,获得积分10
9秒前
YY-Bubble完成签到,获得积分10
9秒前
lulu8809发布了新的文献求助20
9秒前
lJH发布了新的文献求助10
10秒前
莫言完成签到,获得积分10
13秒前
冷艳的道天完成签到 ,获得积分10
15秒前
Angela完成签到,获得积分10
18秒前
lJH完成签到,获得积分10
18秒前
Popeye完成签到,获得积分10
20秒前
pluto应助李李采纳,获得10
23秒前
研友_7ZebY8完成签到,获得积分10
24秒前
合适怡完成签到,获得积分10
24秒前
开朗的慕儿完成签到,获得积分10
24秒前
25秒前
26秒前
我要发财发布了新的文献求助10
27秒前
David完成签到 ,获得积分10
28秒前
NexusExplorer应助小王采纳,获得10
29秒前
30秒前
木卓发布了新的文献求助10
31秒前
小垃圾10号完成签到,获得积分10
31秒前
leolee发布了新的文献求助10
31秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
Research on Disturbance Rejection Control Algorithm for Aerial Operation Robots 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038388
求助须知:如何正确求助?哪些是违规求助? 3576106
关于积分的说明 11374447
捐赠科研通 3305798
什么是DOI,文献DOI怎么找? 1819322
邀请新用户注册赠送积分活动 892672
科研通“疑难数据库(出版商)”最低求助积分说明 815029