Stem Cell and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Stem Cells. 2011 Feb;29(2):344-56. doi: 10.1002/stem.579.
There is growing evidence that Müller glia cells (MGCs) might act as regenerative elements in injured retinas of fishes and amniotes. However, their differentiation potential in humans is yet unknown. We isolated Müller glia from adult human retinas and propagated them in vitro revealing for the first time their ability to differentiate into rod photoreceptors. These results were also confirmed with mice retinas. Here, we describe conditions by which human MGCs adopt a rod photoreceptor commitment with a surprising efficiency as high as 54%. Functional characterization of Müller glia-derived photoreceptors by patch-clamp recordings revealed that their electrical properties are comparable to those of adult rods. Interestingly, our procedure allowed efficient derivation of MGC cultures starting from both injured and degenerating and postmortem human retinas. Human transplanted Müller glia-derived photoreceptors integrate and survive within immunodeficient mouse retinas. These data provide evidence that Müller glia retains an unpredicted plasticity and multipotent potential into adulthood, and it is therefore a promising source of novel therapeutic applications in retinal repair.
越来越多的证据表明,Müller 胶质细胞(MGCs)可能在鱼类和羊膜动物受损的视网膜中充当再生元件。然而,它们在人类中的分化潜力尚不清楚。我们从成人视网膜中分离出 Müller 胶质细胞,并在体外进行培养,首次揭示了它们分化为视杆细胞的能力。这些结果也在小鼠视网膜中得到了证实。在这里,我们描述了使人类 MGC 获得高达 54%的惊人效率的视杆细胞分化的条件。通过膜片钳记录对 Müller 胶质细胞衍生的光感受器进行功能表征表明,它们的电特性与成年视杆细胞相当。有趣的是,我们的程序允许从受伤、退化和死后的人视网膜中高效地获得 MGC 培养物。人移植的 Müller 胶质细胞衍生的光感受器在免疫缺陷小鼠视网膜中整合并存活。这些数据表明 Müller 胶质细胞在成年期保持着出人意料的可塑性和多能性,因此是视网膜修复中新型治疗应用的有前途的来源。