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Neuroprotection by human umbilical cord blood-derived progenitors in ischemic brain injuries.
Archives Italiennes De Biologie ( IF 0.8 ) Pub Date : 2011-6-28 , DOI: 10.4449/aib.v149i2.1370
Hadar Arien-Zakay 1 , Shimon Lecht , Armon Nagler , Philip Lazarovici
Affiliation  

Stem cells have an extremely high potential to treat many devastating diseases, including neuronal injuries. Albeit the need for human neuronal stem cells, their quantities are very limited by relying on early human embryos as the main source. Therefore, progenitors of other origins, such as human umbilical cord blood (CB) are being considered. In the last decade, various populations isolated from the CB were reported to differentiate in vitro towards a neural phenotype. The conditions to induce the cell differentiation are not conclusive and may include addition of chemicals, cytokines and growth factors, including the nerve growth factor (NGF). Some CB cells were found to express the TrkANGF receptor, suggesting an endogenous role for this growth factor also in the CB environment. The ability of CB and derived stem cell populations to protect against neurological deficits was shown, both in vitro and in vivo, in models of ischemic brain injuries. In rodent models of stroke, heatstroke, brain trauma and brain damage at birth, CB cells either by intravenous injection or intrastriatal transplantation, were found to reduce the infarct size and the neurological deficits caused by the injury. The restorative effects of CB were suggested to be mediated by mechanisms other than cell replacement. Some of the proposed mechanisms involve reduced inflammation, nerve fiber reorganization by trophic actions, increased cell survival and enhanced angiogenesis. Furthermore, treatment with CB was found to have a therapeutic window of days compared with the present 36 hour window for the treatment of stroke with clinically available tools such as recombinant tissue plasminogen activator. Considering the encouraging results with whole CB and derived cells transplantation in ischemic injury models and since CB is widely available and have been used clinically, they may be an excellent source of cells for treatment of human brain ischemic disorders.

中文翻译:

人类脐带血祖细胞在缺血性脑损伤中的神经保护作用。

干细胞具有极高的潜力来治疗包括神经元损伤在内的多种破坏性疾病。尽管需要人类神经元干细胞,但由于依赖早期人类胚胎作为主要来源,其数量非常有限。因此,正在考虑其他来源的祖细胞,例如人脐带血(CB)。在过去的十年中,据报道,从CB分离出的各种种群在体外向神经表型分化。诱导细胞分化的条件尚不确定,可能包括添加化学物质,细胞因子和生长因子,包括神经生长因子(NGF)。发现一些CB细胞表达TrkANGF受体,表明该生长因子在CB环境中也具有内源性作用。在缺血性脑损伤模型中,在体外和体内均显示了CB和衍生的干细胞群体预防神经功能缺损的能力。在中风,中暑,脑外伤和出生时脑部损伤的啮齿动物模型中,发现通过静脉内注射或纹状体内移植的CB细胞可减少由损伤引起的梗塞面积和神经功能缺损。CB的修复作用被认为是由细胞替代以外的其他机制介导的。一些提出的机制包括减少炎症,通过营养作用使神经纤维重组,增加细胞存活率和增强血管生成。此外,与目前使用临床上可用的工具(例如重组组织纤溶酶原激活剂)治疗中风的36小时窗相比,使用CB进行治疗具有几天的治疗窗。考虑到在缺血性损伤模型中整个CB和衍生细胞移植的令人鼓舞的结果,并且由于CB广泛可用并已在临床上使用,它们可能是治疗人脑缺血性疾病的绝佳细胞来源。
更新日期:2020-08-21
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