Wednesday, 28 September 2016

Making Microglia

Muffat J, Li Y, Yuan B, Mitalipova M, Omer A, Corcoran S, Bakiasi G, Tsai LH, Aubourg P, Ransohoff RM, Jaenisch R. Efficient derivation of microglia-like cells from human pluripotent stem cells. Nat Med. 2016. doi: 10.1038/nm.4189. [Epub ahead of print]

Microglia, the only lifelong resident immune cells of the central nervous system (CNS), are highly specialized macrophages that have been recognized to have a crucial role in neurodegenerative diseases such as Alzheimer's, Parkinson's and adrenoleukodystrophy (ALD). However, in contrast to other cell types of the human CNS, bona fide microglia have not yet been derived from cultured human pluripotent stem cells. Here we establish a robust and efficient protocol for the rapid production of microglia-like cells from human (h) embryonic stem (ES) and induced pluripotent stem (iPS) cells that uses defined serum-free culture conditions. These in vitro pluripotent stem cell-derived microglia-like cells (termed pMGLs) faithfully recapitulate the expected ontogeny and characteristics of their in vivo counterparts, and they resemble primary foetal human and mouse microglia. We generated these cells from multiple disease-specific cell lines . We further describe a platform to study the integration and live behaviour of pMGLs in organotypic 3D cultures. This modular differentiation system allows for the study of microglia in highly defined conditions as they mature in response to developmentally relevant cues, and it provides a framework in which to study the long-term interactions of microglia residing in a tissue-like environment.

Anyone that works on living animals in the UK has to have ethical approval to justify their work and each year they have to supply numbers of animals used as part of the national statistic.

The UK Government have wanted to get the number of animals used down, but their was a problem with the development of transgenic animals, as this caused the number of animals used to increase.

Many of the transgenic animals do not develop any harms as consequence to their genetic modification, but they are recorded because they are genetically modified, yet one can get a so called "normal" mouse and not record it yet some of the bog standard lab mice have mutations that affect function such as vision and hearing loss that go un-noticed. 

It seems that a fudge is being created to limit the problem of normal transgenic mice and rather that being reported as "mild", "moderate" or "severe" they are being reported as being "sub threshold", which sounds like something below the need to report:-(

However, worst fudges that have been around to that mask the number of animals actually used and this is the use of normal animals, that are killed and tissues used to make cell cultures.

These typically don't count in the statistics and so probably thousands upon thousands of animals don't show up on the records.

I believe they should and likewise people who use animals to kill them for tissues should have to go through the same hoops that people who use living animals. I would suspect that if they had to have the same level of ethical scrutiny and licences required then some of the animal work done may not get done. 

Most notably how do you justify the use of animal cells when you can use human cells instead? 

I think it is more and more difficult to use this argument because it is becoming easier and easier to make human cells and one of these ways is via use and diffentiation of  stem cells. One of the stem cells approach is called induced pluripotent stem cells (iPS cells) 

Here you take a cell like a skin cell and give it growth factors so that it becomes a stem cell capable of growing into any other cell type if you know how to give the right differentiation clues.

In this current study they have found a way to make human microglial-like cells from iPS cells, so you should not need to use rodent cells to study microglia. So a way forward to save our furry friends

Microglia are thought by many to be central to the generation of progressive disease and so the capacity to make human microglia is going to be of value in the search for treatments of progressive MS.


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