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用于进行性多发性硬化症的干细胞疗法

Stem Cell Therapies for Progressive Multiple Sclerosis.

作者信息

Smith Jayden A, Nicaise Alexandra M, Ionescu Rosana-Bristena, Hamel Regan, Peruzzotti-Jametti Luca, Pluchino Stefano

机构信息

Cambridge Innovation Technologies Consulting (CITC) Limited, Cambridge, United Kingdom.

Department of Clinical Neurosciences and National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Cambridge, United Kingdom.

出版信息

Front Cell Dev Biol. 2021 Jul 9;9:696434. doi: 10.3389/fcell.2021.696434. eCollection 2021.

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination and axonal degeneration. MS patients typically present with a relapsing-remitting (RR) disease course, manifesting as sporadic attacks of neurological symptoms including ataxia, fatigue, and sensory impairment. While there are several effective disease-modifying therapies able to address the inflammatory relapses associated with RRMS, most patients will inevitably advance to a progressive disease course marked by a gradual and irreversible accrual of disabilities. Therapeutic intervention in progressive MS (PMS) suffers from a lack of well-characterized biological targets and, hence, a dearth of successful drugs. The few medications approved for the treatment of PMS are typically limited in their efficacy to forms of the disease, have little impact on slowing degeneration, and fail to promote repair. In looking to address these unmet needs, the multifactorial therapeutic benefits of stem cell therapies are particularly compelling. Ostensibly providing neurotrophic support, immunomodulation and cell replacement, stem cell transplantation holds substantial promise in combatting the complex pathology of chronic neuroinflammation. Herein, we explore the current state of preclinical and clinical evidence supporting the use of stem cells in treating PMS and we discuss prospective hurdles impeding their translation into revolutionary regenerative medicines.

摘要

多发性硬化症(MS)是一种中枢神经系统的慢性炎症性疾病,其特征为脱髓鞘和轴突变性。MS患者通常表现为复发缓解型(RR)病程,表现为包括共济失调、疲劳和感觉障碍在内的神经症状的散发性发作。虽然有几种有效的疾病修正疗法能够应对与复发缓解型多发性硬化症(RRMS)相关的炎症复发,但大多数患者将不可避免地进展为以逐渐且不可逆转的残疾累积为特征的进展性病程。进展性MS(PMS)的治疗干预缺乏明确的生物学靶点,因此缺乏成功的药物。少数被批准用于治疗PMS的药物通常疗效仅限于该疾病的某些形式,对减缓退变几乎没有影响,也无法促进修复。为了满足这些未被满足的需求,干细胞疗法的多因素治疗益处尤其引人注目。表面上提供神经营养支持、免疫调节和细胞替代,干细胞移植在对抗慢性神经炎症的复杂病理方面具有巨大潜力。在此,我们探讨支持使用干细胞治疗PMS的临床前和临床证据的现状,并讨论阻碍其转化为革命性再生药物的潜在障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bc0/8299560/22a0aaf4c999/fcell-09-696434-g001.jpg

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