Generation of Functional Neural Artificial Tissue from Human Umbilical Cord Blood Stem Cells

Generation of Functional Neural Artificial Tissue from Human Umbilical Cord Blood Stem Cells
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DOI:
10.1089/ten.tec.2008.0485
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发表时间:
2009-09-01
影响因子:
3
通讯作者:
Domanska-Janik, Krystyna
Domanska-Janik, Krystyna
中科院分区:
医学4区
文献类型:
--
作者:
Jurga, Marcin;Lipkowski, Andrzej W.;Domanska-Janik, Krystyna

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基于干细胞的再生神经病学是治疗中枢神经系统疾病的新兴概念。在各种建议的程序中,最有前途的是用人工神经组织重新填充受损脑实质的囊性空腔。最近的研究表明,在同种异体移植在啮齿类动物中,这些组织工程实体被证明是有效的缺氧/缺血性脑损伤的修复。人脐带血(HUCB)被认为是一种有效且无争议的神经干细胞(NSC)来源。本研究的主要目的是构建人脐静脉内皮细胞源性神经人工组织并研究其功能特性。神经类器官在3周内在人类来源的生物可降解支架上形成,并且类似于其中存在未成熟干细胞(Oct 4+和Sox 2+)和增殖成神经细胞(Nestin+、GFAP+和Ki 67+)的生态位结构。将这种聚集体放置在多电极芯片上并向成熟神经元(TUJ 1+和MAP 2+)分化。与二维培养物相比,这些三维聚集体形成功能电路并产生自发场/动作电位。我们的研究结果表明,三维环境促进HUCB源性神经干细胞的成熟,这是再生医学应用中应该考虑的问题。
Stem cell-based regenerative neurology is an emerging concept for treatment of diseases of central nervous system. Among variety of proposed procedures, one of the most promising is refilling of cystic cavities of injured brain parenchyma with artificial neural tissue. Recent studies revealed that after allogenic transplantation in rodents these tissue-engineered entities were shown efficient in repair of hypoxic/ischemic brain injury. Human umbilical cord blood (HUCB) was recognized to be an efficient and noncontroversial source of neural stem cells (NSC). The main purpose of this study was to generate HUCB-derived neural artificial tissue and investigate their functional properties. Neural organoids formed on human-originated biodegradable scaffolds within 3 weeks and resembled niche structure where immature stem cells (Oct4+ and Sox2+) and proliferating neuroblasts (Nestin+, GFAP+, and Ki67+) were present. Such aggregates were placed on multi-electrode chips and differentiated toward mature neurons (TUJ1+ and MAP2+). These three-dimensional aggregates in contrast to two-dimensional cultures formed functional circuits and generated spontaneous field/action potentials. Our results indicate that three-dimensional environment facilitates maturation of HUCB-derived NSC what should be considered regarding regenerative medicine application.