Aileen Anderson

(Note: video of Dr. Anderson here, made a few weeks before the conference) Her agenda this morning is Stem Cell 101, Nervous System 101, SCI 101, and is timing really everything?

Stem cell 101 . . . these are undifferentiated cells that divide via mitosis, and their daughter cells can either differentiate into adult cells, or remain as stem cells.  When she was in grad school 20 years ago, people didn’t even know that there were stem cells existing in the adult human body.  Big change since then . . .

You can imagine stem cells as being like at the very base of a tree, with more and more differentiation as you move up the trunk and out into the branches.

The nervous system is 3 types of cells: neurons plus oligodendrocytes plus astrocytes.  The neural stem cells they work with can become each of these.

SCI 101 . . . signals not flowing in either direction.  (Yup.)  Getting injured is a longterm and dynamic process.  The injury isn’t the same after day one as it is after day 14, or six months later.

Early thinking about stem cells was to just make new cells and replace the ones that were lost. But there are other tasks they might be good for, like changing the ones that survive — activating them to do their job.  If we assume that we need replacements, what do we need from them?

First, they need to live, survive.  In SCI there’s an epicenter, but there’s also damage far away. Our transplants need to be able to migrate.  Then they need to do only what we want them to do and nothing else.  This is why we do safety trials (Phase 1 trials) — to make sure we’re doing no harm.

They work on the nature of cells, the nurturing of those cells, and the niche into which the cells go.

Their neural stem cells are derived from 16 – 20 weeks gestated human fetal brain.  They sort them based on cell surface markers.

Is timing everything? in 2003 someone published a review of historical literature that suggested there was no point doing transplants right after injury or a long time after injury; the subacute phase was best.  For years after that paper, everyone took it for granted that he was right.  It was logical.  (Okay, she just moved right on from that set up . . . maybe she’ll revisit it later.)

In 2008 the Reeve foundation did a big survey of the SCI community and gathered a lot of information — the most surprising thing was that there were MANY more people living with sci (1.3 million vs. 250,000), which meant that curing it would save a lot more money than had been previously known.

They use “sort of like boy in a bubble” rodents for their experiments to eliminate problems associated with human to mouse transplants.  They put 75,000 cells above and below the injury site . .. in the first week, at 30 days, and at 60 days.  Then they look at what happened to the cells.  Showing a slide that’s a colored cross section of an injured mouse cord that got cells in the chronic phase . . . the cells took on the characteristics of surrounding cells, which is what you want.

In the subacute environment, most of the cells became oligodendrocytes, some were neurons, and a very few were astrocytes.  The cells reach out and integrate into their surroundings.

Video of a little white mouse dragging herself along — she’s untreated.  Second mouse motoring along.  The tests they did later showed that the mouse cells were getting myelinated, and that axons were creating synapses.  They figured out a way to eliminate the human cells they’d put into those mouses — using a substance that was a thousand times more toxic to human cells than to mouse cells.  When they gave that to the treated mice, they lost the recovery they’d gained.

All that was about a subacute phase . . . what about a chronic phase?  Can the timeline be pushed later.  Actually, the cells at chronic phases survived just fine, the majority of them became oligodendrocytes, and very few of them became astrocytes.  Did they help with function?  Yes.

Fast forward . . . you take your findings and do more work, changing variables like crazy in order to show that it wasn’t a fluke.  There are many considerations for human trials:

Timing, dosage, neuropathic pain, multiple models, locus of transplantaion, migration, long term safety, scaling to primates, recover endpoints, molecular switching, AAANNNNDDDD

She stops because now we’re going to hear about clinical trials.

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