CONTROL OF SCHWANN CELL GROWTH

我们建议继续研究Schwann的调节 细胞在发育过程中的增殖，以及对损伤的反应。 我们的先例工作表明：1)轴突表面成分 通过与雪旺细胞直接接触刺激雪旺细胞增殖 细胞表面，2)轴突有丝分裂原含有硫酸乙酰肝素 蛋白多糖作为一种基本成分，3)有丝分裂原活性可以 从它的蛋白多糖成分中解离 纯化，4)雪旺细胞释放成分，可以 刺激雪旺细胞增殖；5)底物结合 材料(尤其是层粘连蛋白)在以下情况下是有效的 血清，在刺激雪旺细胞增殖。我们向您介绍一种 解释这些观察结果可能相互关联的假说 这表明轴突表面蛋白多糖可能是一种 雪旺细胞的有丝分裂原呈现者，以及有丝分裂原 雪旺细胞表面受体可能与一种 层粘连蛋白受体。我们提出了实验计划来测试这一点 假说，以及其他旨在解释 雪旺细胞在完全分化时，对 有丝分裂刺激。这些实验解决的问题 包括1)轴突有丝分裂原在 由雪旺细胞释放的物质成熟？2)是 髓鞘支持雪旺细胞增殖 维持其髓鞘支持作用？为什么不脱髓鞘 沃尔里安时期雪旺细胞相对不增殖 退化，以及什么操作会导致它们的增殖？ 3)雪旺细胞通过什么机制参与调节 它们自身的增殖？4)什么可溶性因子(和底物 结合因子)雪旺细胞是否释放驱动雪旺细胞的物质 在没有轴突的情况下增殖？5)什么是本质 雪旺细胞表面的丝裂原受体；它是否与 有丝分裂原受体？6)方法在扩增中是否有效 啮齿类动物的原代雪旺细胞群体在 扩大灵长类雪旺细胞的原代种群和 人类？我们相信，对相互作用的更好理解 轴突/雪旺细胞/细胞外基质之间的关系 调控雪旺细胞的增殖对于理解 涉及雪旺细胞增殖异常的过程 见于神经纤维瘤病，以及学习如何获得 足够数量的雪旺细胞用于构建细胞 有助于促进三叉神经节和中枢神经系统再生的假体。

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.