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May 16, 2013
 |  BC Innovations  |  Tools & Techniques

Myelination gets direct

Separate groups at the Case Western Reserve University School of Medicine and the Stanford University School of Medicine have developed similar approaches to directly reprogram rodent fibroblasts into oligodendrocyte progenitor cells.1,2 The direct lineage conversion method could be a safe and fast way to supply cells for myelination disorder cell therapies. Now, the teams need to show that their methods also reprogram human fibroblasts.

Myelination disorders include leukodystrophies and autoimmune conditions such as multiple sclerosis (MS). In all cases, loss of the myelin sheaths around axons of neurons impairs nerve firing and causes nervous system deficiencies.

Most available treatments for myelination disorders aim to slow demyelination or treat symptoms, but none repair or replace myelin.

One starting point for that goal is oligodendrocyte progenitor cells (OPCs), which are components of the CNS white matter that generate oligodendrocytes, the cells that produce myelin during development and after injury in the CNS.

But current sources of OPCs are limited to donor and embryonic stem cell tissues, both of which carry risks of immune rejection by the recipient. Donor OPCs also are in short supply, and cells derived from human embryonic stem cells come with a host of ethical issues and concerns about potential teratogenicity.

As an alternative, several groups including a team at Case Western have derived OPCs from rodent fibroblast-derived induced pluripotent stem (iPS) cells.3 iPS cells would be patient specific but require multiple manipulation steps, and the strategy has not yet yielded human OPCs.

The most recent approach for cell differentiation is direct lineage conversion-reprogramming somatic cells into a desired cell type-which eliminates many manipulation steps.

The Stanford team is among the groups that have successfully reprogrammed rodent fibroblasts into neurons and neural stem cells.4

Now, the Case Western and Stanford teams have accomplished direct lineage conversion of mouse fibroblasts into OPCs. In papers published in the same issue...

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