Re: PBMC separation from brain tissue

From: Keith Bahjat (me@keithbahjat.com)
Date: Wed Apr 03 2002 - 00:55:23 EST


Rick,

Instead of worrying about isolating  cells of interest, why don't you
utilize your cytometer as it was designed; to analyze large numbers of cells
rapidly. I don't mean that in a derogatory sense, but just to awaken you to
what the hardware can do. We've all been lulled into thinking that
5000-10000 events per sample is a maximum, and we have to perform enrichment
steps prior to using the cytometer to make sure this holds true. The only
caveats are time and reagents needed (since you'll likely have a larger
volume of cell suspension, you'll need more antibody). Prep that sample and
acquire 1x10^6 events. Acquire 5x10^6 events. Just let it run till you're
sure you have the necessary data. It takes less time to do the correct
experiment once than to do the wrong experiment multiple times.

I would suggest filtering your suspension after your collagenase digestion,
then using an anti-CD45 antibody to resolve the leukocytes from the
surrounding tissues.

And as another note, some component(s) of commercial collagenase
preparations is quite efficient at cleaving certain antigens from the cell
surface (it's not trypsin). We found almost everything was affected to some
degree, but CD4 appeared to be the worst. Limiting the collagenase digest to
30 minutes and transferring immediately to ice cold, EDTA containing buffer
gave the best results in our hands.

I list that as an example of how any handling or processing of the cell
suspension has the potential for altering antigen expression. This is a big
reason why I like to make a single cell suspension and analyze the whole
thing.

Good luck.

Kb
--
Science is built with facts as a house is with stones--but a collection of
facts is no more a science than a heap of stones is a house. -Jules Henry
Poincare (1854-1912)

Keith Bahjat, PhD
Applications Engineering Manager
Cytomation, Inc
Fort Collins, CO
(970) 226-2200 x223
keithb@cytomation.com


on 4/2/02 7:52 AM, Stojan Dimitrov at stoianski_fl@yahoo.com wrote:

>
> Dear Rick,
> Why dont you try using the MACS system.
> http://www.miltenyibiotec.com/index.php?site=products-human
> Using anti-CD45 magnetic MicroBeads (for leucocytes)
> you might separate all cells of hematopoietic origin
> except erythrocytes, platelets and their precursor
> cells.
> Yours,
> Stoyan
>
> --- Rick Arthur Bright <rbright@emory.edu> wrote:
>>
>> I am trying to analyze lymphocytes, monocytes,
>> granulocytes, etc from
>> brain and lung tissues.  After collagenase digestion
>> I, of course, have a
>> lot of junk...stuff I don't want to run through the
>> instrument.
>>
>> What is the best way of separating the cells from
>> the junk?  I tried
>> Ficoll-paque, which nets me the lymphocytes, but I
>> lose other cells types
>> that might be important.
>>
>> Would a Percoll gradient be a better route to go?
>> What gradients would be
>> most appropriate.  I am digging in the literature as
>> well, finding many
>> reference to percoll gradients, but few of them say
>> what the gradients are
>> and where the cells of interest will settle.
>>
>> Any quick thoughts would be helpful.  I, hopefully,
>> will stumble upon that
>> magic reference sometime tonight, but if you know
>> already I would
>> appreciate your help.
>>
>> Thanks
>>
>> Rick
>>
>>
>>
>
>
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