Haas Sebastian, Weidner Norbert, Winkler Jürgen
Department of Neurology, University of Regensburg, Regensburg, Germany.
Curr Opin Neurol. 2005 Feb;18(1):59-64. doi: 10.1097/00019052-200502000-00012.
Acute cerebral infarction causes irreversible locally restricted loss of the neuronal circuitry and supporting glial cells with consecutive functional deficits and disabilities. The currently available and effective therapy targets fast vessel recanalization accompanied by symptomatic measures. Research activities focusing on stem cells, which represent a promising source for organotypic cell replacement and functional recovery after stroke, have gained momentum in recent years, making regenerative cell-based therapies a much more feasible realistic approach. This review provides an update about preclinical and clinical cell-based studies in stroke focusing on stem cells derived from the adult central nervous and hematopoetic systems.
Endogenous neural stem cells, which have been shown to reside throughout life in the central nervous system, have the capacity to replace lost neurons in models for numerous disorders, including cerebral ischemia. Considering adult neural stem cell transplantation as a regenerative strategy after stroke, progress has been made in isolating human adult neural stem cells and demonstrating the feasibility of autologous neural stem cell transplantation. An increasing number of studies provide evidence that hematopoietic stem cells, either after stimulation of endogenous stem cell pools or after exogenous hematopoietic stem cell application (transplantation), improve functional outcome after ischemic brain lesions. Various underlying mechanisms such as transdifferentiation into neural lineages, neuroprotection through trophic support, and cell fusion have been deciphered.
Many preclinical studies employing adult stem cell-based strategies hold great promise. For endogenous approaches the correlate of cell replacement underlying functional improvement needs to be demonstrated. Transplantation approaches on the experimental level need further development before clinical application can be considered.
急性脑梗死会导致神经元回路和支持性神经胶质细胞出现不可逆的局部性缺失，进而引发一系列功能缺陷和残疾。目前可用的有效治疗方法以快速血管再通并辅以对症治疗为目标。近年来，聚焦于干细胞的研究活动发展迅速，干细胞有望用于器官型细胞替代和中风后的功能恢复，这使得基于细胞的再生疗法成为一种更可行的现实方法。本综述提供了有关中风领域临床前和临床细胞研究的最新进展，重点关注源自成人中枢神经系统和造血系统的干细胞。
内源性神经干细胞已被证明终生存在于中枢神经系统中，在包括脑缺血在内的多种疾病模型中具有替代丢失神经元的能力。将成人神经干细胞移植作为中风后的再生策略，在分离人类成人神经干细胞以及证明自体神经干细胞移植的可行性方面已取得进展。越来越多的研究表明，无论是刺激内源性干细胞池还是应用外源性造血干细胞（移植）后，造血干细胞都能改善缺血性脑损伤后的功能结局。已经阐明了多种潜在机制，如向神经谱系的转分化、通过营养支持实现神经保护以及细胞融合。
许多采用基于成人干细胞策略的临床前研究前景广阔。对于内源性方法，需要证明功能改善背后的细胞替代相关性。在考虑临床应用之前，实验水平的移植方法需要进一步发展。
