Center for Stem Cell Biology, Developmental Biology Program, and Cell Biology Program, Sloan-Kettering Institute for Cancer Research, New York, New York, USA.
Stem Cells Transl Med. 2014 Jan;3(1):108-13. doi: 10.5966/sctm.2013-0084. Epub 2013 Dec 5.
There has been considerable progress in obtaining engraftable embryonic stem (ES) cell-derived midbrain dopamine neurons for cell replacement therapy in models of Parkinson's disease; however, limited integration and striatal reinnervation of ES-derived grafts remain a major challenge for future clinical translation. In this paper, we show that enhanced expression of polysialic acid results in improved graft efficiency in correcting behavioral deficits in Parkinsonian mice. This result is accompanied by two potentially relevant cellular changes: greater survival of transplanted ES-derived dopamine neurons and robust sprouting of tyrosine hydroxylase-positive processes into host tissue. Because the procedures used to enhance polysialic acid are easily translated to other cell types and species, this approach may represent a general strategy to improve graft integration in cell-based therapies.
在获得可移植的胚胎干细胞（ES）衍生的中脑多巴胺神经元用于帕金森病模型的细胞替代治疗方面已经取得了相当大的进展；然而，ES 衍生移植物的有限整合和纹状体再支配仍然是未来临床转化的主要挑战。在本文中，我们表明，多涎酸的增强表达可提高移植效率，从而纠正帕金森病小鼠的行为缺陷。这一结果伴随着两个潜在相关的细胞变化：移植的 ES 衍生多巴胺神经元的存活率更高，以及酪氨酸羟化酶阳性过程在宿主组织中的大量发芽。由于增强多涎酸的程序很容易转化为其他细胞类型和物种，因此这种方法可能代表了一种提高细胞治疗中移植物整合的通用策略。
