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STEM CELL THERAPY ITS CHALLENGES, SUCCESSES, FAILURES AND POTENTIAL APPLICATIONS : ON-GOING TRANSLATIONAL RESEARCH

机译:干细胞疗法的挑战,成功,失败和潜在的应用:正在进行的翻译研究

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摘要

Critical cells in human organs of injured genetically diseased or aged populations degenerate due to various reasons, mainly injury, genetic mutations and chronic inflammation. The stem cell-niche in most human organs has a limited ability for cell regeneration. In an adult human body, about a billion cells die every day. In some organs and blood pools, injured or lost cells and tissue sheets (e.g. skin graft) could be replaced and in blood loss, it could be replenished by transfusion. For cellular components of blood, we have developed superb tools, specifically tagging them with gamma-emitting radionuclides, for measuring the cellular half-lives, their survival times, turn-over rates and size of blood pools in healthy volunteers and patients. It is possible now to increase the platelet circulating time in blood of splenomegaly patients by splenectomy, thus decreasing the episodes of bleeding complications resulting in fewer visits to blood bank for platelet transfusions. However, these measurements of cell-survival parameters of blood cells are not possible for other cell types, particularly in some retinal- and neuro-degenerative diseases, where only one specific cell type, e.g. neurons, may be lost. This specific cell could be derived from the embryonic or induced pluripotent stem cells (ESC or iPSC) by differentiation and could be delivered to the affected organs provided the cell-loss is not diffuse over a large area and the cells are not migratory. iPSCs now could be derived easily from skin fibroblasts or blood lymphocytes by transfecting with only four genes. In spite of significant and pioneering developments of cell access from ESCs and iPSCs in the last decade, their optimized differentiation methods and their large scale production, cell therapy faces a tremendous challenge in near future due to poor cell-integration in host organs. At present, attention has been diverted to drug discovery. Successes, failures and potential applications of cell therapy in certain diseases are discussed in this article to draw attention of the energetic young minds, scientists and clinicians to solve this challenging puzzle and give hope to the stroke, heart-attack, diabetic and demented patients for a longer and a better quality of life.
机译:受伤的遗传病患者或老年人群的人体器官中的关键细胞由于各种原因而退化,这些原因主要是伤害,基因突变和慢性炎症。大多数人体器官中的干细胞生态位具有有限的细胞再生能力。在成年人体内,每天约有十亿个细胞死亡。在某些器官和血池中,受损或丢失的细胞和组织片(例如皮肤移植物)可以被替换,而在失血中,可以通过输血来补充。对于血液中的细胞成分,我们已经开发了出色的工具,特别是使用发射伽马射线的放射性核素标记它们,以测量健康志愿者和患者的细胞半衰期,存活时间,周转率和血池大小。现在有可能通过脾切除术增加脾肿大患者血液中的血小板循环时间,从而减少出血并发症的发作,从而减少了因血小板输血而去血库的次数。但是,对于其他细胞类型,尤其是在某些视网膜和神经退行性疾病中,血细胞的细胞存活参数的这些测量是不可能的,在这些疾病中,仅一种特定的细胞类型,例如肝细胞。神经元,可能会丢失。该特定细胞可以通过分化来自胚胎或诱导多能干细胞(ESC或iPSC),并且可以传递给受影响的器官,前提是细胞损失不会在大面积上扩散并且细胞不迁移。现在,仅用四个基因进行转染,就可以很容易地从皮肤成纤维细胞或血液淋巴细胞中获得iPSC。尽管在过去的十年中,ESC和iPSC从细胞获取方面取得了重大而开创性的发展,它们的优化分化方法和大规模生产,由于宿主器官中细胞整合不良,细胞疗法在不久的将来仍面临巨大挑战。目前,注意力已转移到药物发现上。本文讨论了细胞疗法在某些疾病中的成功,失败和潜在应用,以引起精力充沛的年轻思想家,科学家和临床医生的注意,以解决这一难题,并为中风,心脏病,糖尿病和痴呆患者提供希望更长,更好的生活质量。

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  • 来源
    《Science and Culture》 |2016年第10期|278-294|共17页
  • 作者

    MRINAL K. DEWANJEE;

  • 作者单位

    National Eye Institute, National Institutes of Health, Bethesda, MD 20892, U.S.A;

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  • 正文语种 eng
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