Arien-Zakay Hadar, Lecht Shimon, Nagler Armon, Lazarovici Philip
The School of Pharmacy Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.
Arch Ital Biol. 2011 Jun;149(2):233-45. doi: 10.4449/aib.v149i2.1370.
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.
干细胞在治疗包括神经元损伤在内的许多毁灭性疾病方面具有极高的潜力。尽管对人类神经干细胞有需求，但由于主要依赖早期人类胚胎作为来源，其数量非常有限。因此，正在考虑其他来源的祖细胞，如人类脐带血（CB）。在过去十年中，据报道从脐带血中分离出的各种细胞群体在体外可分化为神经表型。诱导细胞分化的条件尚无定论，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）。一些脐带血细胞被发现表达TrkANGF受体，这表明该生长因子在脐带血环境中也具有内源性作用。在缺血性脑损伤模型中，无论是在体外还是体内，都显示了脐带血及其衍生的干细胞群体预防神经功能缺损的能力。在中风、中暑、脑外伤和出生时脑损伤的啮齿动物模型中，通过静脉注射或纹状体内移植的脐带血细胞被发现可减少梗死面积以及损伤引起的神经功能缺损。脐带血的修复作用被认为是通过细胞替代以外的机制介导的。一些提出的机制包括减轻炎症、通过营养作用进行神经纤维重组、增加细胞存活和增强血管生成。此外，与目前使用重组组织型纤溶酶原激活剂等临床可用工具治疗中风的36小时窗口期相比，发现用脐带血治疗有几天的治疗窗口。考虑到在缺血性损伤模型中全脐带血及其衍生细胞移植取得的令人鼓舞的结果，并且由于脐带血广泛可得且已在临床上使用，它们可能是治疗人类脑缺血性疾病的极佳细胞来源。
