Platelet bioreactor: accelerated evolution of design and manufacture.
Platelet bioreactor: accelerated evolution of design and manufacture.
复制标题
DOI：
10.1080/09537104.2016.1265922
复制
发表时间：
2017-07
期刊：
影响因子：
3.3
通讯作者：
Beaulieu LM
中科院分区：
文献类型：
--
作者：
Thon JN;Dykstra BJ;Beaulieu LM
负责血栓形成和血管修复的血小板是由骨髓中的巨核细胞产生的。血小板对止血和伤口愈合至关重要，通常在手术、化疗和重大创伤后提供。尽管血小板很重要，但今天的血小板完全来自人类志愿者捐赠者。它们的保质期只有五天，这使得血小板短缺在长周末、公民假期、恶劣天气以及最需要血小板的重大紧急情况下很常见。骨髓中的巨核细胞通过血管中的缝隙/窗口挤出被称为原血小板的长细胞质延伸部分，从而产生血小板。前血小板通过顺序释放血小板和大的盘状血小板中间体(称为前血小板)进入循环，作为生产血小板的装配线。血小板生物反应器的最新进展旨在模拟骨髓的关键生理特征，包括细胞外基质组成/硬度、包括组织特异性微血管内皮细胞的血管结构和剪切力。然而，三维(3D)微环境中复杂的相互作用如何调控血小板生成仍然知之甚少，与设计和制造仿生微流控设备相关的技术挑战往往被低估和报道不足。我们之前已经回顾了主要的细胞培养、血小板质量评估以及必须克服的调节障碍，以使人的血小板生产能够用于临床。这篇综述建立在我们先前手稿的基础上：(1)详细介绍了血小板生物反应器设计的历史演变，以概括天然血小板的体外生产，以及(2)确定相关的挑战，这些挑战仍然需要解决，以进一步扩大和验证这些设备的商业应用。虽然血小板是最早在体外生产的细胞之一，在微流控设计方面引领了重大的工程进步，但由此产生的发现无疑将延伸到生产其他人类组织。这项工作对于确定驱动细胞分化的相关3D组织特定微环境的生理特征并详细说明这些微环境在疾病中是如何被破坏的至关重要。这是一个新兴的领域，其未来不仅将决定体外生产血小板和开发针对血小板减少症的靶向治疗方法，而且还将决定下个世纪再生医学的前景。
Platelets, responsible for clot formation and blood vessel repair, are produced by megakaryocytes in the bone marrow. Platelets are critical for hemostasis and wound healing, and are often provided following surgery, chemotherapy, and major trauma. Despite their importance, platelets today are derived exclusively from human volunteer donors. They have a shelf life of just five days, making platelet shortages common during long weekends, civic holidays, bad weather, and during major emergencies when platelets are needed most. Megakaryocytes in the bone marrow generate platelets by extruding long cytoplasmic extensions called proplatelets through gaps/fenestrations in blood vessels. Proplatelets serve as assembly lines for platelet production by sequentially releasing platelets and large discoid-shaped platelet intermediates called preplatelets into the circulation. Recent advances in platelet bioreactor development have aimed to mimic the key physiological characteristics of bone marrow, including extracellular matrix composition/stiffness, blood vessel architecture comprising tissue-specific microvascular endothelium, and shear stress. Nevertheless, how complex interactions within three-dimensional (3D) microenvironments regulate thrombopoiesis remains poorly understood, and the technical challenges associated with designing and manufacturing biomimetic microfluidic devices are often under-appreciated and under-reported. We have previously reviewed the major cell culture, platelet quality assessment, and regulatory roadblocks that must be overcome to make human platelet production possible for clinical use. This review builds on our previous manuscript by: (1) detailing the historical evolution of platelet bioreactor design to recapitulate native platelet production ex vivo, and (2) identifying the associated challenges that still need to be addressed to further scale and validate these devices for commercial application. While platelets are among the first cells whose ex vivo production is spearheading major engineering advancements in microfluidic design, the resulting discoveries will undoubtedly extend to the production of other human tissues. This work is critical to identify the physiological characteristics of relevant 3D tissue-specific microenvironments that drive cell differentiation and elaborate upon how these are disrupted in disease. This is a burgeoning field whose future will define not only the ex vivo production of platelets and development of targeted therapies for thrombocytopenia, but the promise of regenerative medicine for the next century.
登录
查看更多内容
DOI：
10.1083/jcb.201304054
发表时间：
2013-06-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Machlus KR;Italiano JE Jr
通讯作者：
Italiano JE Jr
影响因子：
3
作者：
Lasky, Larry C.;Sullenbarger, Brent
通讯作者：
Sullenbarger, Brent
影响因子：
5.9
作者：
Feng, Qiang;Shabrani, Namrata;Thon, Jonathan N.;Huo, Hongguang;Thiel, Austin;Machlus, Kellie R.;Kim, Kyungho;Brooks, Julie;Li, Feng;Luo, Chenmei;Kimbrel, Erin A.;Wang, Jiwu;Kim, Kwang-Soo;Italiano, Joseph;Cho, Jaehyung;Lu, Shi-Jiang;Lanza, Robert
通讯作者：
Lanza, Robert
影响因子：
44.1
作者：
通讯作者：
--
影响因子：
6.1
作者：
Regehr KJ;Domenech M;Koepsel JT;Carver KC;Ellison-Zelski SJ;Murphy WL;Schuler LA;Alarid ET;Beebe DJ
通讯作者：
Beebe DJ