Survival and Functionality of Human Induced Pluripotent Stem Cell-Derived Oligodendrocytes in a Nonhuman Primate Model for Multiple Sclerosis

Abstract

This study demonstrates for the first time that human induced pluripotent stem cell (iPSC)-derived oligodendrocyte precursor cells (OPCs), after intracortical implantation in a nonhuman primate model for progressive multiple sclerosis (MS), migrate to the lesions and remyelinate denuded axons. These findings imply that human iPSC-OPCs can be a therapeutic tool for MS. The results of this feasibility study on the potential use of hiPSC-derived OPCs are of great importance for all MS researchers focusing on the stimulation of remyelination in MS patients. Further optimization and research on practical issues related to the safe production and administration of iPSC-derived cell grafts will likely lead to a first clinical trial in a small group of secondary progressive MS patients. This would be the first specific therapeutic approach aimed at restoring myelination and rescuing axons in MS patients, since there is no treatment available for this most debilitating aspect of MS.

Xeno‐free culture for generation of forebrain oligodendrocyte precursor cells from human pluripotent stem cells

“…The efficacy of OPC transplantation has been demonstrated to rescue brain function through remyelination in several mouse disease models including those of congenital hypomyelination (Wang et al, 2013), radiation myelopathy (Piao et al, 2015), diffuse axonal injury (Xu et al, 2015), and multiple sclerosis (Thiruvalluvan et al, 2016), and a clinical trial for SCI based on OPC transplantation has been initiated (Lebkowski, 2011;Priest et al, 2015). Moreover, the xeno-free derivation of OPCs from hPSCs is expected to facilitate and accelerate the clinical translation of these cells (Rodrigues et al, 2017;Sundberg et al, 2011;Yamashita et al, 2017).…”

The future is now: cutting edge science and understanding toxicology

“…Devine and Patani also describe the latest progress in scaling up the production of therapeutically relevant cell types derived from iPSCs for cell therapy applications, for example, developing 3D cultures that allow the harvesting of billions of uniform, mature neurons from a single flask (Rigamonti et al 2016). The most recent approaches for iPSC-based cell therapy were also described, such as the intracerebral injection of human iPSC-derived oligodendrocytes to treat primate models of multiple sclerosis (Thiruvalluvan et al 2016). Our opinion is that discussions of the applications of iPSCs and cell reprogramming strategies are especially relevant for CBT, because of their potential to be utilized for disease modeling and predictive toxicity for candidate therapeutics.…”

Application of CRISPR/Cas9 to the study of brain development and neuropsychiatric disease

“…Because many subtypes of neurons and glia have been implicated in neuropsychiatric disease (Gotter et al, 2001), it is crucial to study defined cell types, both alone and in combination, in order to understand how they function in health and disease. While discussed in great detail by others (reviewed in Ho et al, 2015), a variety of protocols have reported differentiation or induction of glutamatergic (Zhang et al, 2013, Ho et al, 2016), GABAergic (Sun et al, 2016), dopaminergic (Theka et al, 2013), and serotonergic (Lu et al, 2016) neurons, as well as astrocytes (Emdad et al, 2012), oligodendrocytes (Espinosa-Jeffrey et al, 2016; Thiruvalluvan et al, 2016), and microglia-like cells (Muffat et al, 2016). …”