Presents

DAILY DIGEST

REPORTING FROM ACTRIMS

Americas Committee for Treatment and Research in Multiple Sclerosis
West Palm Beach, Florida

FRIDAY, FEBRUARY 28

Experiments of Human Glial Stem Cell Transplants in Mice Suggests Potential Path to Remyelination in Multiple Sclerosis

WEST PALM BEACH, FL — Remyelination has been an elusive goal in multiple sclerosis (MS) research. Recent studies in mice conducted by John Mariani, PhD, and colleagues showed that implanting human glial progenitor (stem) cells (hGPCs) into demyelinated brains of mice can lead to complete remyelination in the animal brains. The research, while still in the pre-clinical stages, suggests there is potential down the road for future benefit in humans using transplanted glial progenitor cells.

Human glial progenitor cells (hGPCs), or stem cells, are able to differentiate into oligodendrocytes and remyelinate different types of demyelinated brain tissue in mice. University of Rochester researcher John Mariani, PhD, reported the findings at the ACTRIMS Forum on February 27.Patricia K. Coyle, MDDr. Mariani, a research scientist at the Center for Translational Neuromedicine at University of Rochester in Rochester, NY, presented his data on Thursday, February 27, at the ACTRIMS Forum in West Palm Beach, Florida.

Glial cells are the most abundant cells in the central nervous system (CNS), surrounding the neurons and providing support and insulation as well as other functions. Oligodendrocytes, a type of glial cell, are the sole source of myelin in the adult CNS, and their loss or dysfunction is central to a variety of diseases including MS. Dr. Mariani's earlier line of research used fetal hGPCs. These studies showed that the stem cells were able to broadly disperse after implantation and remyelinate the diffusely demyelinated CNS in adult animals. "Fetal hGPCs effectively remyelinated congenitally hypomyelinated adult axons, and axons that had been acutely demyelinated in adulthood, using two different mouse models," he explained.

"Transplanted hGPCs proved both highly migratory and robustly myelinogenic in the adult [mouse] brain," Dr. Mariani reported. "By 12 to 15 weeks after transplant, the injected cells had dispersed broadly throughout the forebrain."

The next step was to determine whether human GPCs already present within the mouse brain would be able to differentiate as oligodendrocytes and proceed with the task of remyelination. "Resident hGPCs could myelinate not only axons that had never been myelinated—as in the adult shiverer mouse brain—but also those that were previously ensheathed by myelin," Dr. Mariani and colleagues reported in a paper in BioRxiv. "By 46 weeks of age (36 weeks post-transplant) much if not most of the forebrain white matter in these previously cuprizone demyelinated [mouse] brains was of human origin."

"Thus, human GPCs were able to effectively remyelinate mature axons that had been previously myelinated in the brain, and could do so even when delivered to the adult brain after the onset of demyelination," he said. This research is not ready for human trials, Dr. Mariani told the ACTRIMS Forum audience, but studies are in preparation in other animal models. "Taken together, transplantation of human glial progenitor cells in the adult demyelinated brain may serve as an effective therapeutic approach in progressive MS," he concluded.

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By Katherine Wandersee, for the Consortium of Multiple Sclerosis Centers (CMSC)

© 2020, Consortium of Multiple Sclerosis Centers. Published by Delaware Media Group, LLC. All rights reserved. None of the contents may be reproduced in any form without prior written permission from the publisher. The opinions expressed in this publication are those of the presenters and do not necessarily reflect the opinions or recommendations of their affiliated institutions, the publisher, or Bristol-Myers Squibb.

Human glial progenitor cells (hGPCs), or stem cells, are able to differentiate into oligodendrocytes and remyelinate different types of demyelinated brain tissue in mice. University of Rochester researcher John Mariani, PhD, reported the findings at the ACTRIMS Forum on February 27.Patricia K. Coyle, MDDr. Mariani, a research scientist at the Center for Translational Neuromedicine at University of Rochester in Rochester, NY, presented his data on Thursday, February 27, at the ACTRIMS Forum in West Palm Beach, Florida.

Patricia K. Coyle, MD

Patricia K. Coyle, MD

Patricia K. Coyle, MD

Patricia K. Coyle, MD

Patricia K. Coyle, MD