Is this the end for animal work on myelinating cells…it should be.

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Recently there has been a debate on whether humans myelinate like animals and the suggestion was that in MS they may not. Yet we are ploughing huge resource into animal experiments to find repair agents for humans

To work on animals, you typically have to have ethical approval and in Europe you need to consider reduction, refinement and replacement of animals in research. Each year we have to report to the UK Home Office, who regulate animal experiments in UK, how many animals we experiment on. However, there is a fudge they created so that the number of animal experiments do not look so big. If you kill the animal and then do work in a test tube on the cells you get from an animal you don’t have to report it or get ethical approval to do so. This a crazy situation because thousands upon thousands of animals are used each year by people who can give no consideration to the 3Rs. Typically to do nerve and oligodendrocyte work you often use animals shortly after birth or just before birth when the cells can be grown most easily. However, if there are alternatives to using animals to try and understand human biology then the ethical argument is that these need to be done. You can’t use the it is cheaper to use animals argument in the eyes of the Home Office/regulators for live animal experiements, so why do resarchers working on cell culture get away with it? It is the simplest way to reduce animal numbers by regulating this type of study.

You can now make oligodendrocytes from human stem cells and so there should be no argument for doing animal experiments. Do you need zebra fish, mice or rats when you should be working on human tissues? I am sure you can make a case in some conditions, but for a lot of the experiments I suspect you can’t really. What will the funders do?

García-León JA, García-Díaz B, Eggermont K, Cáceres-Palomo L, Neyrinck K, Madeiro da Costa R, Dávila JC, Baron-Van Evercooren A, Gutiérrez A, Verfaillie CM. Generation of oligodendrocytes and establishment of an all-human myelinating platform from human pluripotent stem cells. Nat Protoc. 2020 Oct 23. doi: 10.1038/s41596-020-0395-4.

Oligodendrocytes (OLs) are responsible for myelin production and metabolic support of neurons. Defects in OLs are crucial in several neurodegenerative diseases including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). This protocol describes a method to generate oligodendrocyte precursor cells (OPCs) from human pluripotent stem cells (hPSCs) in only ~20 d, which can subsequently myelinate neurons, both in vitro and in vivo. To date, OPCs have been derived from eight different hPSC lines including those derived from patients with spontaneous and familial forms of MS and ALS, respectively. hPSCs, fated for 8 d toward neural progenitors, are transduced with an inducible lentiviral vector encoding for SOX10. The addition of doxycycline for 10 d results in >60% of cells being O4-expressing OPCs, of which 20% co-express the mature OL marker myelin basic protein (MBP). The protocol also describes an alternative for viral transduction, by incorporating an inducible SOX10 in the safe harbuor locus AAVS1, yielding ~100% pure OPCs. O4+ OPCs can be purified and either cryopreserved or used for functional studies. As an example of the type of functional study for which the derived cells could be used, O4+ cells can be co-cultured with maturing hPSC-derived neurons in 96/384-well-format plates, allowing the screening of pro-myelinating compounds.

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