Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Clinical Neuroimmunology Unit and Multiple Sclerosis CSUR, Department of Neurology. "Virgen de la Arrixaca" Clinical University Hospital, IMIB-Arrixaca, Murcia, Spain; Universidad Católica San Antonio de Murcia (UCAM), Murcia, Spain.
Stem Cell Res. 2021 May;53:102319. doi: 10.1016/j.scr.2021.102319. Epub 2021 Apr 15.
The advent of cellular reprogramming technology converting somatic cells into induced pluripotent stem cells (iPSCs) has revolutionized our understandings of neurodegenerative diseases that are otherwise hard to access and model. Multiple Sclerosis (MS) is a chronic demyelinating, inflammatory disease of central nervous system eventually causing neuronal death and accompanied disabilities. Here, we report the generation of several relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) iPSC lines from MS patients along with their age matched healthy controls from peripheral blood mononuclear cells (PBMC). These patient specific iPSC lines displayed characteristic embryonic stem cell (ESC) morphology and exhibited pluripotency marker expression. Moreover, these MS iPSC lines were successfully differentiated into neural progenitor cells (NPC) after subjecting to neural induction. Furthermore, we identified the elevated expression of cellular senescence hallmarks in RRMS and PPMS neural progenitors unveiling a novel drug target avenue of MS pathophysiology. Thus, our study altogether offers both RRMS and PPMS iPSC cellular models as a good tool for better understanding of MS pathologies and drug testing.
细胞重编程技术将体细胞转化为诱导多能干细胞(iPSC)的出现,彻底改变了我们对神经退行性疾病的认识,否则这些疾病很难被研究和建模。多发性硬化症(MS)是一种慢性脱髓鞘、炎症性中枢神经系统疾病,最终导致神经元死亡和残疾。在这里,我们从 MS 患者和年龄匹配的健康对照者的外周血单核细胞(PBMC)中报告了几种复发性缓解型 MS(RRMS)和原发性进展型 MS(PPMS)iPSC 系的生成。这些患者特异性 iPSC 系显示出典型的胚胎干细胞(ESC)形态,并表现出多能性标记物的表达。此外,这些 MS iPSC 系在经过神经诱导后成功分化为神经祖细胞(NPC)。此外,我们发现 RRMS 和 PPMS 神经祖细胞中细胞衰老特征的表达升高,揭示了 MS 病理生理学的新药物靶点途径。因此,我们的研究提供了 RRMS 和 PPMS iPSC 细胞模型,作为更好地理解 MS 病理学和药物测试的良好工具。