W.M. Keck Center for Collaborative Neuroscience, Rutgers, State University of New Jersey, 604 Allison Rd., Piscataway, NJ 08854-8082, USA.
Exp Neurol. 2011 May;229(1):72-9. doi: 10.1016/j.expneurol.2010.08.028. Epub 2010 Sep 17.
Olfactory ensheathing cells (OEC), which normally associate closely with but do not myelinate axons in situ, myelinate axons in the adult mammalian spinal cord. They are of clinical interest as candidate cells for autologous transplantation but the ability of OEC to myelinate axons in vitro has been controversial. To clarify this issue, we isolated OEC from olfactory bulbs (OB) of juvenile and adult rats expressing GFP and analyzed their ability to myelinate axons. Using a well-defined assay for myelination of dorsal root ganglia (DRG) axons in culture, we found that OEC from juvenile pups associated with and then myelinated DRG axons. OEC assembled into bundles with the axons by 1week and required more than a week before myelination on axons was detected. In contrast, rat Schwann cells did not bundle axons and they formed P0(+) and MBP(+) myelin segments after as little as 1week. Most of the OEC in culture exhibited staining for calponin, a marker that was not found on Schwann cells in culture, whereas in both OEC and Schwann cell populations nearly all cells were positive for p75NTR and GFAP. These results confirm previous reports showing only subtle immunological differences between Schwann cells and OEC. Besides differences in the rate of myelination, we detected two additional functional differences in the interactions of OEC and Schwann cells with DRG axons. First, the diameter of OEC generated myelin was greater than for Schwann cell myelin on DRG axons. Second, OEC but not Schwann cells myelinated DRG axons in the absence of vitamin C. OEC isolated from adult OB were also found to bundle and myelinate DRG axons but the latter occurred only after incubation times of at least 3weeks. The results indicate that adult OEC require longer incubation times than juvenile OEC to myelinate axons and suggest that patterns of myelination by OEC and Schwann cells are distinguishable at least on axons in vitro. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.
嗅鞘细胞(OEC)通常与轴突密切相关,但不在原位形成髓鞘,而在成年哺乳动物脊髓中形成髓鞘。它们作为自体移植的候选细胞具有临床意义,但 OEC 在体外形成髓鞘的能力一直存在争议。为了澄清这一问题,我们从表达 GFP 的幼年和成年大鼠嗅球(OB)中分离出 OEC,并分析了它们形成髓鞘的能力。使用一种明确的体外培养背根神经节(DRG)轴突髓鞘形成测定法,我们发现幼年大鼠 OEC 与 DRG 轴突结合,然后形成髓鞘。OEC 在 1 周内与轴突形成束,并在检测到轴突形成髓鞘之前需要超过 1 周的时间。相比之下,大鼠 Schwann 细胞不会使轴突成束,它们在 1 周后形成 P0(+)和 MBP(+)髓鞘段。培养物中的大多数 OEC 表现出 calponin 染色,这是培养物中 Schwann 细胞没有的标记物,而在 OEC 和 Schwann 细胞群体中,几乎所有细胞都对 p75NTR 和 GFAP 呈阳性。这些结果证实了之前的报道,即 Schwann 细胞和 OEC 之间只有细微的免疫学差异。除了髓鞘形成速度的差异外,我们还检测到 OEC 和 Schwann 细胞与 DRG 轴突相互作用的另外两个功能差异。首先,OEC 形成的髓鞘的直径大于 Schwann 细胞形成的 DRG 轴突上的髓鞘。其次,OEC 而不是 Schwann 细胞在没有维生素 C 的情况下使 DRG 轴突形成髓鞘。从成年 OB 分离出的 OEC 也被发现使 DRG 轴突成束并形成髓鞘,但这仅发生在孵育时间至少为 3 周后。结果表明,成年 OEC 比幼年 OEC 需要更长的孵育时间来形成髓鞘,并且表明 OEC 和 Schwann 细胞的髓鞘形成模式至少在体外的轴突上是可区分的。本文是一个特刊的一部分,该特刊题为:了解嗅鞘胶质细胞及其对神经系统修复的前景。