You are hereDecember 5, 2016 | ESCs/iPSCs
Success for iPSC-OPCs in a Non-human Primate Model of Multiple Sclerosis
Review of “Survival and Functionality of Human Induced Pluripotent Stem Cell-Derived Oligodendrocytes in a Nonhuman Primate Model for Multiple Sclerosis” from Stem Cells Translational Medicine by Stuart P. Atkinson
Endogenous oligodendrocyte precursor cells (OPCs) can restore lost oligodendrocytes and repair damage to the myelin sheaths which protect axons during the early stages of the autoimmune disease multiple sclerosis (MS). However, endogenous OPCs lose this ability during later chronic progressive stages of the disease and many have proposed that the exogenous production and transplantation of OPCs as a novel treatment strategy .
OPCs derived from patient-specific induced pluripotent stem cells (iPSCs) may be the ideal cell type, but while studies employing small animal models have reported functional and clinical applicability (See original text for extensive references), none of these models fully recapitulates human MS.
In a new Stem Cells Translational Medicine study, the enterprising team of Sjef Copray (University Medical Center Groningen, Netherlands) have now studied the transplantation of human iPSC-derived OPCs into the cerebral cortex of a non-human primate (marmosets) with experimental autoimmune encephalomyelitis (EAE), considered the best animal model of MS .
The authors first employed a previously described protocol  which produced GFP-labelled iPSC-OPCs that developed into mature oligodendrocytes with the ability to extensively myelinate dorsal root ganglia neuron axons during in vitro co-culture experiments.
Before moving to the marmoset model, the study first assessed responses in used a mouse model exhibiting selective oligodendrocyte death and extensive demyelination in the corpus callosum. Analysis three weeks after iPSC-OPC grafting demonstrated good survival, migration, and signs of oligodendrocyte differentiation and successful remyelination. Following this success, the study then assessed iPSC-OPC grafting in an EAE mouse model, and this displayed a reduction in symptoms, a reduction in immune cell infiltration, and a reduction in the level of demyelination. However, the observed lack of exogenous grafted cells in the lesion site suggests that the beneficial effects of iPSC-OPCs derive from the action of secreted factors (e.g. HGF, TFG- and IL-6) and not from the direct action of oligodendrocytes.
And so to the REALLY interesting part! What happened after grafting into the marmoset EAE model? iPSC-OPCs survived, migrated, and differentiated into mature myelin basic protein (MBP)-expressing oligodendrocytes (See Figure – Arrow points to GFP/MBP double positive cells) which interacted with host axons and formed thin myelin sheaths.
Success! hiPSC-derived OPCs seem to have just what it takes to treat the debilitating symptoms of chronic progressive MS. The authors of this excellent study hope that further studies related to the safe production and administration of iPSC-derived cells can lead to a human MS trial. Stay tuned to the Stem Cells Portal to find out if they succeed!
- Goldman SA, Nedergaard M, and Windrem MS. Glial progenitor cell-based treatment and modeling of neurological disease. Science 2012;338:491-495.
- Thiruvalluvan A, Czepiel M, Kap YA, et al. Survival and Functionality of Human Induced Pluripotent Stem Cell-Derived Oligodendrocytes in a Nonhuman Primate Model for Multiple Sclerosis. Stem Cells Translational Medicine 2016;5:1550-1561.
- Hu Z, Li T, Zhang X, et al. Hepatocyte growth factor enhances the generation of high-purity oligodendrocytes from human embryonic stem cells. Differentiation 2009;78:177-184.