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Development of a Novel Electromagnetic Rewarming Technology for the Cryopreservation of Stem Cells with Large Volume 大体积干细胞低温保存的电磁复温新技术的发展
Pub Date : 2020-11-10 DOI: 10.5772/intechopen.94556
Shen Ren, Z. Shu, Jiaji Pan, Ji Peng, Junlan Wang, Chunhua Zhao, D. Gao
Applications of stem cells have been playing significant roles in scientific and clinical settings in the last few decades. The foundation of these approaches is successful cryopreservation of stem cells for future use. However, so far we can only cryopreserve stem cell suspension of small volumes in the order of 1 mL mostly due to the lack of an effective rewarming technique. Rapid and uniform rewarming has been approved to be beneficial, and sometimes, indispensable for the survival of cryopreserved stem cells, inhibiting ice recrystallization or devitrification. Unfortunately, the conventional water bath thawing method failed in providing the rapid and uniform rewarming. The conversion of electromagnetic (EM) energy into heat provides a possible solution to this problem. This chapter will focus on (1) analysis of the combined EM and heat transfer phenomenon in the rewarming of a biospecimen, (2) numerical investigation of the rewarming system, (3) practical setup of an EM resonance system, and (4) test of heating performance with large volume of cells.
在过去的几十年里,干细胞的应用在科学和临床环境中发挥了重要作用。这些方法的基础是成功冷冻保存干细胞以备将来使用。然而,由于缺乏有效的复温技术,到目前为止,我们只能低温保存1ml左右的小体积干细胞悬浮液。快速和均匀的再加热已被证实是有益的,有时对冷冻保存的干细胞的存活是必不可少的,可以抑制冰重结晶或脱氮。遗憾的是,传统的水浴解冻方法不能提供快速和均匀的复温。将电磁能转化为热能为这个问题提供了一个可能的解决方案。本章将着重于(1)分析生物标本再加热过程中电磁与传热的结合现象,(2)再加热系统的数值研究,(3)电磁共振系统的实际设置,以及(4)大体积细胞的加热性能测试。
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引用次数: 2
Combined Application Therapies of Stem Cells and Drugs in the Neurological Disorder Attenuation 干细胞与药物联合应用治疗神经系统疾病
Pub Date : 2020-10-30 DOI: 10.5772/intechopen.94484
Chia-Chi Chen, Ying-Ching Hung, Chia-Yu Lin, Hsiao-Yun Chen, Ping-Min Huang, S. Hung
Neurological disorders (NDs) are diseases of the central and peripheral nervous system that affected the hundreds of millions of people worldwide. Temporal lobe epilepsy (TLE) is a common NDs with hallucinations and disturbance of consciousness that cause the abnormal neurological activity in any part of brain. Neuroinflammation (NI) has been identified in epilepsy-related tissue from both experimental and clinical evidence and suspected to participate in the formation of neuronal cell death, reactive gliosis and neuroplastic changes in the hippocampus, may contribute to epileptogenesis. The NI is tightly regulated by microglia, but it is thought that excessive or chronic microglial activation can contribute to neurodegenerative processes. Therefore, the modulation of microglia responses may provide a therapeutic target for the treatment of severe or chronic NI conditions. Although the condition responds well to antiepileptic drugs (AEDs), there are still unresponsive to AEDs in about 1/3 of cases. Neural stem cells are the origin of various types of neural cells during embryonic development. Currently, many results of stem cell therapies in the animal experiments and clinical trials were demonstrated the efficacious therapeutic effects in the attenuated symptoms of ND. Therefore, the combined application therapies of stem cells and drugs may be a promising candidate for the therapeutic strategies of NDs, especially TLE.
神经系统疾病(NDs)是影响全世界数亿人的中枢和周围神经系统疾病。颞叶癫痫(TLE)是一种常见的伴有幻觉和意识障碍的神经性疾病,可引起大脑任何部位的神经活动异常。从实验和临床证据来看,神经炎症(NI)已经在癫痫相关组织中被发现,并被怀疑参与神经元细胞死亡、反应性胶质增生和海马神经可塑性改变的形成,可能有助于癫痫的发生。NI受小胶质细胞的严格调控,但过度或慢性的小胶质细胞激活可导致神经退行性过程。因此,调节小胶质细胞反应可能为治疗严重或慢性NI疾病提供治疗靶点。尽管抗癫痫药物(aed)对该病反应良好,但仍有大约1/3的病例对aed无反应。神经干细胞是胚胎发育过程中各类神经细胞的来源。目前,干细胞疗法在动物实验和临床试验中的许多结果都证明了对ND症状的有效治疗效果。因此,干细胞与药物联合应用治疗可能是NDs特别是TLE治疗策略的一个很有前景的候选方案。
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引用次数: 0
Induced Pluripotent Stem Cells from Animal Models: Applications on Translational Research 来自动物模型的诱导多能干细胞:在转化研究中的应用
Pub Date : 2020-10-27 DOI: 10.5772/intechopen.94199
Laís Vicari de Figueiredo Pessôa, Naira Caroline Godoy Pieri, K. Recchia, Fabiana Fernandes Bressan
Over the history of humankind, knowledge acquisition regarding the human body, health, and the development of new biomedical techniques have run through some animal model at some level. The mouse model has been primarily used as the role model for a long time; however, it is severely hampered regarding its feasibility for translational outcomes, in particular, to preclinical and clinical studies. Herein we aim to discuss how induced pluripotent stem cells generated from non-human primates, pigs and dogs, all well-known as adequate large biomedical models, associated or not with gene editing tools, can be used as models on in vivo or in vitro translational research, specifically on regenerative medicine, drug screening, and stem cell therapy.
在人类历史上,关于人体、健康和新生物医学技术的知识获取在某种程度上贯穿于一些动物模型中。长期以来,老鼠模型一直被主要用作角色模型;然而,它在转化结果方面的可行性受到严重阻碍,特别是在临床前和临床研究方面。在这里,我们的目标是讨论如何从非人类灵长类动物,猪和狗中产生的诱导多能干细胞,这些都是众所周知的足够大的生物医学模型,与基因编辑工具相关或不相关,可以用作体内或体外转化研究的模型,特别是再生医学,药物筛选和干细胞治疗。
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引用次数: 1
Challenges for Deriving Hepatocyte-Like Cells from Umbilical Cord Mesenchymal Stem Cells for In Vitro Toxicology Applications 从脐带间充质干细胞中提取肝细胞样细胞用于体外毒理学应用的挑战
Pub Date : 2020-06-24 DOI: 10.5772/intechopen.91794
A. Serras, M. Cipriano, P. Silva, J. Miranda
The in vitro toxicology field seeks for reliable human relevant hepatic models for predicting xenobiotics metabolism and for the safety assessment of chemicals and developing drugs. The low availability and rapid loss of the phenotype or low biotransformation activity of primary hepatocytes urged the stem cell differentiation into hepatocyte-like cells (HLCs). Umbilical cord-derived mesenchymal stem cells (UC-MSC), in particular, offer a highly available cell source, with few ethical issues and higher genetic stability. However, the dynamic and complex microenvironment of liver development, including the cell-ECM and cell–cell interactions, pressure gradients (oxygen and nutrients) and growth factor signaling that are critical for the differentiation and maturation of hepatocytes, challenges the progress of in vitro hepatic models. Promising strategies like (i) cytokine and growth factor supplementation mimicking the liver development; (ii) epigenetic modification; and (iii) bioengineering techniques to recreate the liver microphysiological environment are gaining increasing importance for the development of relevant in vitro liver models to address the need for higher predictivity and cost efficiency. In this context, this chapter reviews the existing knowledge and recent advances on the approaches for deriving HLCs from UC-MSC and their application for in vitro toxicology.
体外毒理学领域寻求可靠的与人类相关的肝脏模型,以预测外源性代谢,评估化学品的安全性和开发药物。原代肝细胞的低可利用性和表型的快速丧失或低生物转化活性促使干细胞向肝细胞样细胞(hlc)分化。特别是脐带间充质干细胞(UC-MSC),提供了一种高度可用的细胞来源,几乎没有伦理问题和更高的遗传稳定性。然而,肝脏发育的动态和复杂的微环境,包括细胞- ecm和细胞-细胞相互作用,压力梯度(氧和营养)和生长因子信号,这些对肝细胞的分化和成熟至关重要,对体外肝脏模型的进展提出了挑战。有前景的策略,如(i)细胞因子和生长因子的补充模拟肝脏发育;(ii)表观遗传修饰;(iii)重建肝脏微生理环境的生物工程技术对于相关体外肝脏模型的开发越来越重要,以满足更高的预测性和成本效率的需求。在此背景下,本章综述了UC-MSC衍生hcc的现有知识和最新进展及其在体外毒理学中的应用。
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引用次数: 2
Umbilical Cord Blood and Cord Tissue Bank as a Source for Allogeneic Use 脐带血和脐带组织库作为同种异体使用的来源
Pub Date : 2020-03-11 DOI: 10.5772/intechopen.91649
T. Nagamura-Inoue, F. Nagamura
Recently, umbilical cord blood (CB) has received attention as the allogeneic optimum source for immunotherapies. More recently, the umbilical cord (UC) has been rapidly utilized as an abundant source of mesenchymal stromal cells (MSCs), which migrate toward the inflammatory and damaged tissue to subside the inflammation and support tissue repair. Both CB and UC can be provided “off-the-shelf” cell products for immunotherapies and regenerative medicine. As biomedical wastes, CB and UC can be obtained noninvasively without any risks to the donor. CB cells and UC-derived MSCs (UC-MSCs) also have higher proliferation potentials than other cells obtained from adult tissues. In addition, UC-MSCs are less immunogenic and have significant immunosuppressive ability. Several clinical trials with CB or UC-MSCs have been conducted based on these advantages. The establishment of a stable supply system of CB and UC-MSCs is critical now for their utilization in regenerative and immune cell therapies. We have thus established the cord blood/cord bank, “IMSUT CORD,” as a new type of biobank, to supply both frozen CB and UC tissues and derived cells for research and clinical uses. In this chapter, we will introduce the overall flow from collection to shipment and discuss several issues that need to be resolved in unrelated allogeneic stable supply system.
近年来,脐带血作为免疫治疗的异体最佳来源而受到关注。最近,脐带(UC)被迅速用作间充质基质细胞(MSCs)的丰富来源,它们向炎症和受损组织迁移,以减轻炎症并支持组织修复。CB和UC都可以为免疫治疗和再生医学提供“现成的”细胞产品。作为生物医学废物,CB和UC可以无创获取,对供体没有任何风险。CB细胞和uc来源的间充质干细胞(UC-MSCs)也比从成人组织中获得的其他细胞具有更高的增殖潜力。此外,UC-MSCs的免疫原性较低,具有明显的免疫抑制能力。基于这些优势,已经开展了几项针对CB或UC-MSCs的临床试验。建立稳定的骨髓间充质干细胞和UC-MSCs供应系统是目前将其用于再生和免疫细胞治疗的关键。因此,我们建立了脐带血/脐带血库,“IMSUT cord”,作为一种新型的生物库,为研究和临床用途提供冷冻脐带血和UC组织和衍生细胞。在本章中,我们将介绍从收集到运输的整个流程,并讨论在不相关的同种异体稳定供应系统中需要解决的几个问题。
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引用次数: 3
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Novel Perspectives of Stem Cell Manufacturing and Therapies
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