The M1/M2 thing is still used as a shorthand to describe aggregate cell behavior when simplicity of explanation is desirable, but is really not taken seriously anymore with regard to single cells. That is, there's a lot of evidence that while certain groups of proteins are more likely to promote inflammation and certain groups to suppress it/promote regeneration, there's too much overlap in any given cell to say that this cell is an "M1" or "M2" cell. The functional ambiguity of the microglia is fascinating, and I've been putting a lot of my effort there recently. I'm becoming more and more convinced that some regenerative therapies that our lab has developed act on the microglia as the most upstream event. That might be crackpot, on the other hand.
For sure, I've just seen a couple talks / papers now that describe some (non-cytokine) receptor as being the thing that polarizes cells in one direction or the other and I find it somewhat garbage science, at least in the Alzheimer's field. Especially since there does't seem to be any real consensus on how they're defined. The microglia you're talking about in this context are with regards to young blood treatments?
Not exactly. My work focuses on the use of mesenchymal cells to treat brain injuries, primarily stroke. Recently we've been using the exosomes that the MSCs spit out as a proxy for MSC therapy. Exosomes appear to promote recovery in rodents and primates just as effectively as the parent cells themselves. Cell targeting is a difficult thing to pin down, because being ~50-100nm, exosomes are difficult to tag and track with any real precision. To the extent we have been able to track them, they seem to target the microglia in the vicinity of the lesion more than any other cell type. Been doing some mechanistic studies recently trying to probe what exactly the effect of "feeding" exosomes from MSC to microglia is. The "young blood" thing (really young bone marrow) is a side business that sprang out of work that mk and I have done together for many years.