BioPharmaNet-DIMORFIPA National Institute of Biostructures and Biosystems, University of Bologna, Italy.
J Mol Endocrinol. 2010 Jan;44(1):13-23. doi: 10.1677/JME-09-0067. Epub 2009 Jul 3.
Brain and spinal cord repair is a very difficult task in view of the extremely limited repair capability of the mature central nervous system (CNS). Thus, cellular therapies are regarded as a new frontier for both acute and chronic neurological diseases characterized by neuron or oligodendroglia degeneration. Although cell replacement has been considered as the primary goal of such approaches, in recent years greater attention has been devoted to the possibility that new undifferentiated cells in damaged nervous tissue might also act in autocrine-paracrine fashion, regulating the micro-environment through the release of growth factor and cytokines, also regulating immune response and local inflammation. In this review, repair of demyelinating disease using endogenous cells will be discussed in view of the critical role played by thyroid hormones (THs) during developmental myelination, focusing on the following points: 1) endogenous stem and precursor cells during demyelinating diseases; 2) TH homeostasis in the CNS; 3) cellular and molecular mechanism regulated by TH during developmental myelination and 4) a working hypothesis to develop a rationale for the use of THs to improve remyelination through endogenous stem and precursor cells in the course of demyelinating diseases.
鉴于成熟中枢神经系统(CNS)的修复能力极其有限,脑和脊髓修复是一项非常困难的任务。因此,细胞疗法被认为是急性和慢性神经疾病的新前沿,这些疾病的特征是神经元或少突胶质细胞退化。尽管细胞替代已被认为是此类方法的主要目标,但近年来,人们越来越关注受损神经组织中未分化细胞也可能以自分泌-旁分泌方式发挥作用的可能性,通过释放生长因子和细胞因子来调节微环境,还调节免疫反应和局部炎症。在这篇综述中,鉴于甲状腺激素 (THs) 在发育性髓鞘形成过程中发挥的关键作用,将讨论使用内源性细胞修复脱髓鞘疾病,重点关注以下几点:1)脱髓鞘疾病期间的内源性干细胞和前体细胞;2)CNS 中的 TH 动态平衡;3)TH 在发育性髓鞘形成过程中调节的细胞和分子机制;4)一个工作假设,以开发使用 TH 来通过内源性干细胞和前体细胞改善脱髓鞘疾病过程中的髓鞘再生的原理。