CONTROL OF SCHWANN CELL GROWTH

我们建议继续研究雪旺氏细胞的调节 在发育过程中的细胞增殖，以及对损伤的反应。 我们先前的工作表明：1）轴突表面成分 刺激雪旺细胞增殖， 细胞表面，2）这种轴突有丝分裂原含有硫酸乙酰肝素 蛋白聚糖作为必需成分，3）促分裂原活性可 从其蛋白聚糖组分中解离出来， 纯化，4）雪旺细胞释放成分， 刺激雪旺细胞增殖，和5）底物结合 材料（特别是层粘连蛋白）是有效的， 血清刺激雪旺细胞增殖。 我们提出了一个 解释这些观察结果如何相互关联的假设 这表明轴突表面蛋白聚糖可能是一种 施旺细胞的有丝分裂原呈递者， 许旺细胞表面的受体可能与一种 层粘连蛋白受体 我们提出了实验计划来测试这一点 假设，以及其他旨在解释如何 当完全分化时，雪旺氏细胞变得对 促有丝分裂刺激 这些实验所要解决的问题 包括1）轴突有丝分裂原是否因 雪旺细胞释放的物质使其成熟 2)是 髓鞘支持能够增殖的雪旺细胞， 维持其髓磷脂的支持作用 为什么非髓鞘形成 Wallarian期雪旺细胞相对不增殖 退化，什么样的操纵会导致它们增殖？ 3)许旺细胞通过什么机制参与调节 自身的扩散？ 4)哪些可溶性因子（和底物 雪旺氏细胞释放哪些结合因子驱动雪旺氏细胞 在没有轴突的情况下增殖 5)的本质是什么 施旺细胞表面的有丝分裂原受体;它是否与 有丝分裂原受体 6)将方法有效地扩大 啮齿类动物中的原代雪旺细胞群可用于 扩增来自灵长类动物的雪旺细胞的原代群体， 人类吗 我们相信，更好地理解这些相互作用， 轴突/雪旺细胞/细胞外基质之间的作用， 调节雪旺细胞增殖对于理解 涉及雪旺细胞增殖异常的过程， 在神经纤维瘤病，以及学习如何获得 足够数量的许旺细胞，用于构建细胞 用于促进PNS和CNS再生的假体。

We propose continuation of studies of the regulation of Schwann cell proliferation during development, and in response to injury. Our precedent work has shown that 1) an axonal surface component stimulates Schwann cell proliferation by direct contact between cell surfaces, 2) this axonal mitogen contains a heparan sulfate proteoglycan as an essential component, 3) mitogen activity can become dissociated from its proteoglycan component during purification, 4) Schwann cells release components which can stimulate Schwann cell proliferation, and 5) substrate bound materials (especially laminin) are effective, in the presence of serum, in stimulating Schwann cell proliferation. We present a hypothesis to explain how these observations may be interrelated which proposes that the axonal surface proteoglycan may be a mitogen presenter for the Schwann cell, and that the mitogen receptor on the Schwann cell surface may be closely related to a laminin receptor. We present plans for experiments to test this hypothesis, as well as other experiments designed to explain how the Schwann cell, when fully differentiated, becomes refractory to mitogenic stimulation. The questions these experiments address include 1) Is the axonal mitogen rendered less effective with maturation by materials released from Schwann cells? 2) Is the myelin supporting Schwann cell capable of proliferation while maintaining its myelin supporting role? Why are non-myelinating Schwann cells relatively non-proliferative during Wallarian degeneration, and what manipulation will cause them to proliferate? 3) By what mechanisms do Schwann cells contribute to regulation of their own proliferation? 4) What soluble factors (and substrate bound factors) do Schwann cells release which drive Schwann cell proliferation in the absence of axons? 5) What is the nature of the mitogen receptor on the Schwann cell surface; is it linked to the mitogen receptor? 6) Will methods effective in expanding populations of primary Schwann cells in rodents be useful in expanding primary populations of Schwann cells from primates and humans? We believe that a better understanding of the interactions between axon/Schwann cell/extracellular matrix operative to regulate Schwann cell proliferation will be vital to understanding processes involving abnormalities of Schwann cell proliferation as seen in neurofibromatosis, as well as in learning how to obtain adequate numbers of Schwann cells with which to construct cellular prostheses useful in fostering regeneration in the PNS and CNS.