Generation of RRMS and PPMS specific iPSCs as a platform for modeling Multiple Sclerosis.

Journal: Stem Cell Research
Published:
Abstract

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.

Authors
Naresh Mutukula, Zhiqiu Man, Yuta Takahashi, Francisca Iniesta Martinez, Mariana Morales, Ester Carreon Guarnizo, Rocio Hernandez Clares, David Garcia Bernal, Llanos Martinez, Jeronimo Lajara, Estrella Nuñez Delicado, Jose Meca Lallana, Juan Izpisua Belmonte