A comprehensive human leukocyte antigen analysis of 36 782 cord blood units stored in the Australian Public Cord Blood Banking Network

Background and aimsThe network of public cord blood banks (CBBs) in Australia, known as AusCord, comprises CBBs located in Brisbane, Sydney and Melbourne. A novel comprehensive analysis has been performed to determine whether the cryopreserved, searchable cord blood unit (CBU) inventory of approximately 36 000 units share similar tissue types or haplotypes.MethodsHuman leukocyte antigen (HLA) data was analysed using Microsoft Excel following standardisation of typing data.ResultsThe analysis has found that the majority of stored, searched and released CBU exhibit a tissue type that is unique within and between the CBBs. Therefore, each collection performed by the CBBs is likely to comprise a tissue type that is not already stored among the total AusCord inventory. HLA alleles (HLA-A*34, HLA-B*56, HLA-DRB1*08:03), which are uncommon in European populations, were associated with Pacific Islander and/or Indigenous Australian populations and confirmed to be more frequent among donors who, when screened, self-identified as these ethnicities.ConclusionsThese data indicate that (i) continued addition of CBU to existing inventories is likely to further increase the HLA diversity and (ii) screening donors for ethnicity or strategically locating collection sites where ethnic minorities reside can successfully result in collection of rare HLA associated with ethnic minority groups for whom finding donors might otherwise be more difficult.     

Equity, Utility, and the Marketplace: Emerging Ethical Issues of Umbilical Cord Blood Banking in Australia

Over the past decade, umbilical cord blood (UCB) has routinely been used as a source of haematopoietic stem cells for allogeneic stem cell transplants in the treatment of a range of malignant and non-malignant conditions affecting children and adults. UCB banks are a necessary part of the UCB transplant program, but their establishment has raised a number of important scientific, ethical and political issues. This paper examines the scientific and clinical evidence that has provided the basis for the establishment of UCB banks. We also discuss the major ethical issues that UCB banks raise, including ownership of cord blood, processes for obtaining consent for its collection and storage, and confidentiality. Finally, we review other concerns about commercial non-altruistic banking, including concerns about social justice, equity of access and equity of care.     

Artificial Cornea and the Future of Eye Banking

A report on the construction of functional human corneal equivalent reflects a step towards creation of an artificial cornea. We discuss the current status of supply and demand for corneas for transplanation, and wonder if the creation of an artificial cornea will have an effect on corneal transplantation in the near future     

European Association of Tissue Banks Standards for Cryopreserved Cardiovascular Tissue Banking

The Cardiovascular Tissue Banking Standards are designed as an addition to the General Standards of the European Association of Tissue Banks to provide a minimum acceptable level for the donation, processing, storage, testing, labelling and distribution of cardiac tissue throughout Europe. The aim is that all heart valve banks in Europe should work to these Standards so that heart valves can be exchanged between countries without having to check the individual protocols of the donor processing facility. The writing of the Standards has been performed by the Heart Valve Council of EATB with input from cardiac surgeons. It is proposed that once the Standards are accepted they will form the document on which EATB may accredit tissue banks in the future and may form the basis on which National Legislation for Tissue Banking is based.     

抗生物被膜类医用植入材料的未来发展展望

生物被膜极大提高了微生物本身的耐药性(比浮游态细菌高1000-倍)和对环境的适应能力(温度、压强、氧化剂、以及p H),而另一方面医用材料本身会导致异物入侵造成的机体免疫力下降。因而,生物被膜给医用材料植入带来了更大的感染风险,也推动了医用抑菌材料的不断改进和发展。对医用材料中微生物组成的研究以及生物被膜形成机理的逐步揭示成为了抑菌材料发展的导向。抑菌材料的改性主要通过更换材质和形成涂层等方式来改变材料表面的物化性质,其中涂层法是目前被大量尝试的热点。本文简要介绍了医药材料在安全性方面面临的问题以及生物被膜理论研究的主要成果,并详细讨论了抗生素、抑菌金属离子、氧化剂、群体感应淬灭分子、酶等被尝试用于材料涂层抑制生物被膜形成的原理、实例、以及优劣。最后,本文对未来抗生物被膜类抑菌材料的发展趋势进行了展望。     

Strategies for Analysis of the Glycosylation of Proteins: Current Status and Future Perspectives

More than half of human proteins are glycosylated by a bewildering array of complex and heterogeneous N- and O-linked glycans. They function in myriad biological processes, including cell adhesion and signalling and influence the physical characteristics, stability, function, activity and immunogenicity of soluble glycoproteins. A single protein may be glycosylated differently to yield heterogenous glycoforms. Glycosylation analysis is of increasing interest in biomedical and biological research, the pharmaceutical and healthcare industry and biotechnology. This is because it is increasingly apparent that glycosylation changes in diseases, such as cancer, making it a promising target for development of clinically useful biomarkers and therapeutics. Furthermore, as the non-human cells employed in expression systems glycosylate their proteins very differently to human cells, and as glycosylation changes unpredictably under changing environmental conditions, glycans analysis for quality control, optimum efficacy and safety of recombinant glycoproteins destined for human therapeutic use is paramount. The complexities of carbohydrate chemistry make analysis challenging and while there are a variety of robust methodologies available for glycan analysis, there is currently a pressing need for the development of new, streamlined, high throughput approaches accessible to non-specialist laboratories.     

Contrast Enhanced Ultrasound Imaging for Assessment of Spinal Cord Blood Flow in Experimental Spinal Cord Injury

Reduced spinal cord blood flow (SCBF) (i.e., ischemia) plays a key role in traumatic spinal cord injury (SCI) pathophysiology and is accordingly an important target for neuroprotective therapies. Although several techniques have been described to assess SCBF, they all have significant limitations. To overcome the latter, we propose the use of real-time contrast enhanced ultrasound imaging (CEU). Here we describe the application of this technique in a rat contusion model of SCI. A jugular catheter is first implanted for the repeated injection of contrast agent, a sodium chloride solution of sulphur hexafluoride encapsulated microbubbles. The spine is then stabilized with a custom-made 3D-frame and the spinal cord dura mater is exposed by a laminectomy at ThIX-ThXII. The ultrasound probe is then positioned at the posterior aspect of the dura mater (coated with ultrasound gel). To assess baseline SCBF, a single intravenous injection (400 µl) of contrast agent is applied to record its passage through the intact spinal cord microvasculature. A weight-drop device is subsequently used to generate a reproducible experimental contusion model of SCI. Contrast agent is re-injected 15 min following the injury to assess post-SCI SCBF changes. CEU allows for real time and in-vivo assessment of SCBF changes following SCI. In the uninjured animal, ultrasound imaging showed uneven blood flow along the intact spinal cord. Furthermore, 15 min post-SCI, there was critical ischemia at the level of the epicenter while SCBF remained preserved in the more remote intact areas. In the regions adjacent to the epicenter (both rostral and caudal), SCBF was significantly reduced. This corresponds to the previously described “ischemic penumbra zone”. This tool is of major interest for assessing the effects of therapies aimed at limiting ischemia and the resulting tissue necrosis subsequent to SCI.     

Predicting the Future: Review of Public Perception Studies of Nanotechnology

Public perception may have a strong impact on the progress of nanotechnology. A comprehensive risk assessment should therefore take the public into account. This article reviews the social science research examining public perception of nanotechnology. Factors that are important for shaping public perception are described, and applications that could pose acceptance problems are identified. Possibilities and limits of research dealing with future acceptance of nanotechnology are discussed. Implications for industry and science are outlined.     

Spinal Cord Injury: Animal Models,Imaging Tools and the Treatment Strategies

Spinal cord injury (SCI) often leads to irreversible neuro-degenerative changes with life-long consequences. While there is still no effective therapy available, the results of past research have led to improved quality of life for patients suffering from partial or permanent paralysis. In this review we focus on the need, importance and the scientific value of experimental animal models simulating SCI in humans. Furthermore, we highlight modern imaging tools determining the location and extent of spinal cord damage and their contribution to early diagnosis and selection of appropriate treatment. Finally, we focus on available cellular and acellular therapies and novel combinatory approaches with exosomes and active biomaterials. Here we discuss the efficacy and limitations of adult mesenchymal stem cells which can be derived from bone marrow, adipose tissue or umbilical cord blood and its Wharton’s jelly. Special attention is paid to stem cell-derived exosomes and smart biomaterials due to their special properties as a delivery system for proteins, bioactive molecules or even genetic material.

     

Frozen Cord Blood Hematopoietic Stem Cells Differentiate into Higher Numbers of Functional Natural Killer Cells In Vitro than Mobilized Hematopoietic Stem Cells or Freshly Isolated Cord Blood Hematopoietic Stem Cells

Adoptive natural killer (NK) cell therapy relies on the acquisition of large numbers of NK cells that are cytotoxic but not exhausted. NK cell differentiation from hematopoietic stem cells (HSC) has become an alluring option for NK cell therapy, with umbilical cord blood (UCB) and mobilized peripheral blood (PBCD34⁺) being the most accessible HSC sources as collection procedures are less invasive. In this study we compared the capacity of frozen or freshly isolated UCB hematopoietic stem cells (CBCD34⁺) and frozen PBCD34⁺ to generate NK cells in vitro. By modifying a previously published protocol, we showed that frozen CBCD34⁺ cultures generated higher NK cell numbers without loss of function compared to fresh CBCD34⁺ cultures. NK cells generated from CBCD34⁺ and PBCD34⁺ expressed low levels of killer-cell immunoglobulin-like receptors but high levels of activating receptors and of the myeloid marker CD33. However, blocking studies showed that CD33 expression did not impact on the functions of the generated cells. CBCD34⁺-NK cells exhibited increased capacity to secrete IFN-γ and kill K562 in vitro and in vivo as compared to PBCD34⁺-NK cells. Moreover, K562 killing by the generated NK cells could be further enhanced by IL-12 stimulation. Our data indicate that the use of frozen CBCD34⁺ for the production of NK cells in vitro results in higher cell numbers than PBCD34⁺, without jeopardizing their functionality, rendering them suitable for NK cell immunotherapy. The results presented here provide an optimal strategy to generate NK cells in vitro for immunotherapy that exhibit enhanced effector function when compared to alternate sources of HSC.     

Economic Analysis of Vaccination Strategies for PRRS Control

Porcine reproductive and respiratory syndrome virus (PRRSv) is a swine-specific pathogen that causes significant increases in production costs. When a breeding herd becomes infected, in an attempt to hasten control and elimination of PRRSv, some veterinarians have adopted a strategy called load-close-expose which consists of interrupting replacement pig introductions into the herd for several weeks (herd closure) and exposing the whole herd to a replicating PRRSv to boost herd immunity. Either modified-live virus (MLV) vaccine or live field-virus inoculation (FVI) is used. This study consisted of partial budget analyses to compare MLV to FVI as the exposure method of load-close-expose program to control and eliminate PRRSv from infected breeding herds, and secondly to estimate benefit / cost of vaccinating sow herds preventatively. Under the assumptions used in this study, MLV held economic advantage over FVI. However, sensitivity analysis revealed that decreasing margin over variable costs below $ 47.32, or increasing PRRSv-attributed cost above $18.89 or achieving time-to-stability before 25 weeks resulted in advantage of FVI over MLV. Preventive vaccination of sow herds was beneficial when the frequency of PRRSv infection was at least every 2.1 years. The economics of preventative vaccination was minimally affected by cost attributed to field-type PRRSv infection on growing pigs or by the breeding herd productivity level. The models developed and described in this paper provide valuable tools to assist veterinarians in their efforts to control PRRSv.     

Future Strategies on Glioma Research: From Big Data to the Clinic

<正>Glioma,as the most common and aggressive malignant central nervous system(CNS)tumor with generally poor prognosis,has been attracting much attention in the last decade[1].Temozolomide was firstly available in the United States in1999 as a chemotherapy drug for treating brain cancers and remains as the first-line treatment for glioma.The World     

羟乙基淀粉沉淀(HES)法分离脐血造血干细胞的临床优势分析

目的:探讨羟乙基淀粉沉淀(HES)法分离脐血单个核细胞(MNCs)的效果。方法:采集脐血31份,应用羟乙基淀粉(HES)沉淀飞和密度离心(Ficoll)法分离脐血MNCs,、纯化CD3+细胞、CD14+细胞、CD34+细胞,以台盼蓝拒染法检测细胞活力。结果:HES法MNCs回收率、CFU-GM计数高于Ficoll法(85.29±3.79 VS 47.06±4.61,t=35.67,P0.05;67.31±11.57/l×105MNCs VS28.54±6.39/l×105MNCs,t=16.33,P0.05);HES法分离的MNCs中CD3+、CD14+、CD34+细胞数均高于Ficoll法(t=5.76,t=2.51,t=6.67,P0.05)。结论:HES法分离MNCs可获得较好的回收率,是人脐血干细胞理想的分离方法。     

利用人脐带血干细胞制备人鼠肝组织嵌合体模型

目的利用人脐带血干细胞研究制备HBV感染人鼠嵌合小鼠模型。方法将人脐血干细胞,经尾静脉分两次注射到裸鼠体内。分别于第7,14,21天取肝组织,进行AFP免疫组织化学检测,分析人肝细胞在裸鼠体内嵌合生长情况,并进行乙肝病毒感染实验,定量检测感染后小鼠血清中AFP、ALB。结果实验组小鼠在第7、14、21天肝脏内AFP持续阳性表达,AFP表达于细胞质内。HBV感染后小鼠肝脏HBsAg组化显示密集成片的阳性细胞。实验组和对照组表达差异显著（P〈0.05）。结论将人脐血干细胞移植裸鼠肝脏内可以存活并分化成人肝细胞形成嵌合鼠,并能被HBV感染。