Many nerves inside and outside the central nervous system are insulated by a sheath rich in a protein called “myelin.” This myelin-enriched sheath greatly increases the speed at which nerve impulses travel through these nerves. You have probably experienced such fast nerve impulse conduction. Remember the last time you had your hands in water that was overly hot. First there was a very sharp pain that caused you to withdraw your hand as fast as you could, but it was followed by a dull ache that became more and more painful until it abated. This is an example of the fast-moving pain impulses that help protect our limbs from further damage and the slower moving pain impulses that convey the dull ache associated with soft tissue damage.
In some cases the myelin sheath is damaged, or, in some cases, people are born with damaged myelin sheaths. Either way, such a condition is catastrophic, and multiple sclerosis is an example of a disease that results from progressive damage to and loss of the myelin sheath. Spinal cord injuries also strip the myelin sheath from many neurons, thus decreasing the effectiveness with which nerve impulses are conducted. The loss of the myelin sheath can also, in some cases, causes the death of the nerve.
Can the myelin sheath be replaced? Almost certainly. Cells make the myelin sheath and this is a cue for regenerative medicine. Many different types of stem cells can differentiate into myelin sheath-making cells. Embryonic stem cells, for example, can be differentiated into myelin sheath-making cells. This was the basis for Geron Corporation’s clinical trial with embryonic stem cell (ESC)-derived cells that could make myelin sheaths. Myelin sheath-making cells in the central nervous system are known as “oligodendrocytes,” and “oligodendrocyte progenitor cells,” which are mercifully abbreviated OPCs, give rise to oligodendrocytes. Differentiation of ESCs into OPCs led to the Geron clinical trial. However, Geron prematurely terminated this trial, and it is unclear if these embryonic stem cell-derived OPCs can restore sensation and nerve function to spinal cord injury patients.
Other cells, however, can form OPCs, and one of these is induced pluripotent stem cells (iPSCs). Since these cells are derived from the patient’s own cells, they should be recognized by the immune system as part of the patient’s own tissue and not a foreign group of cells.
Su Wang and colleagues from Steven Goldman’s lab at the Center for Translational Neuromedicine at the University of Rochester in Rochester, NY, have made patient-specific iPSCs from which they made patient-specific OPCs. Wang and his colleagues devised a protocol to differentiate human induced pluripotent stem cells (hiPSCs) into OPCs.
In this publication, Wang and others made three hiPSC lines, from which they made human OPCs. They used a very convenient methods to isolate the OPCs – fluorescence-activated cell sorting. hiPSC OPCs differentiated very efficiently into oligodendrocytes and other cell types found in the nervous system.
Next, Wang and others used their iPSC-derived OPCs to recoat nerves of mutant mice that lack myelin sheaths. Mice that have the “shiverer” mutation lack meylin sheaths, and they shake and shiver as a result of it. When implanted with Wang and companies’ iPSC-derived OPCs, these cells recoated with nerves very efficiently. When they compared the efficiency of the iPSC-derived OPCs with that of fetal OPCs, the iPSC-derived OPCs were clearly superior. The recoating of the nerves definitely increased the survival of the siverer mice. No tumors were observed in any of the mice implanted with iPSC-derived OPCs. implanted mice.
Goldman said of this study, “This study strongly supports the utility of hiPSCs as a feasible and effective source of cells to treat myelin disorders.” Goldman continued: “The new population of OPCs and oiligodendrocytes was dense, abundant, and complete. In fact, the re-myelination process appeared more rapid and efficient than with other cell sources.” This is significant because Goldman’s team also made OPCs from ESCs and their iPSC-derived OPCs outperformed the ESC-derived OPCs as well.
Goldman is part of a collaborative research consortium with scientists from Rochester, Syracuse, and Buffalo that wants to conduct a clinical trial that uses OPCs to treat patients with multiple sclerosis. This research group is called the Upstate MS Consortium and the early stages of this study are scheduled to begin in 2015, and it will focus on cells derived from various tissue sources. Goldman anticipates that his HiPSCs-derived OPCs will be included in this project.