Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells.
Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells.
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DOI：
10.3389/fnins.2013.00194
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发表时间：
2013-10-24
影响因子：
4.3
通讯作者：
Miller SL
中科院分区：
文献类型：
--
作者：
Castillo-Melendez M;Yawno T;Jenkin G;Miller SL
在研究、临床和更广泛的社区中，人们对使用干细胞来减少进展或修复脑损伤有很大的兴趣。围产期脑损伤可能是由于在胎儿发育过程中、出生过程中或新生儿期持续的急性或慢性损伤所致。围产期脑损伤最容易识别的结果是脑瘫，然而，这只是轻度至重度神经功能缺损的一系列后果之一。正如我们所回顾的那样，现在全世界都在进行针对脑瘫的干细胞疗法的临床试验。这些试验可能需要很多年才能得出强有力的循证结果。随着这些试验的进行，解决干细胞样细胞在防止新生儿大脑损伤或再生方面的生理基础是适当和及时的。适当的实验动物模型最适合提供这些信息。细胞可用性、免疫排斥的可能性、伦理和后勤考虑，以及天然细胞形成畸胎瘤的倾向，使得胚胎或胎儿干细胞不太可能实用。幸运的是，这些问题与人类羊膜上皮细胞（hAEC）或脐带血（UCB）干细胞的使用无关，这些干细胞可以从出生时丢弃的胎盘和脐带中轻松经济地获得。这些细胞有可能移植到被诊断或甚至怀疑脑损伤的新生儿身上。我们将探索hAEC和未分化的UCB细胞，以及UCB衍生的内皮祖细胞（EPCs）和间充质干细胞（MSCs）的新特性，以及免疫调节和抗炎特性是这些细胞共同的主要作用机制，这反过来又可能改善脑缺氧和炎症，这是围产期脑损伤发病机制的最终途径。
In the research, clinical, and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however, this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical, and logistical considerations, together with the propensity for native cells to form teratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs), or umbilical cord blood (UCB) stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs), and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain injury.
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