Re: Re: CD34 pos. stem cell enumeration question

From: Jáksó Pál (Pal.Jakso@aok.pte.hu)
Date: Fri Nov 16 2001 - 09:48:45 EST


Dear Rob,

First of all thanks for your extensive help. My step by step answers to
your questions are:

"Currently, the only accurate way to measure the absolute CD34+ cell
content
of a sample, both before AND after cryopreservation, is to perform single
platform analyses, i.e., use a counting bead-based flow assay."
I totally agree with you and that's why I introduced it in our
laboratory.

"Incidentally, why are you enumeratiing CD34+ cells in marrow to begin
with?  Graft adequacy for
marrow transplants was not traditionally assessed by flow techniques, but
more usually by 'weighing the bag' and performing a crude leukocyte count
thereon.  Later, CFC assays were performed and an adequate dose was
established based upon the numbers of Colony-Forming-Cells/Kg patient
weight."
I'm  a biologist not a medical doctor and I think this question should
have been adressed to our haematologists in the hospital and I will ask
for their opinion surely.

"To better help you, we need to know what methodology you are using to
count
CD34+ cells."
I use our  own non-ProCount protocol. Briefly: we stain the blood, PBSC,
or bone marrow with CD45 and CD34 in the TruCount tube. After 20 minutes
we add 0,5 ml FACS Lysing Solution  and incubate for 15 minutes. Finally
we measure on a FACSort ( without any washing steps of course). We
acquire and analyse with CellQuest. In order to count most accurately
the CD34 pos. cells I use a complex gating strategy combining blast
gates from the FSC/SCC, CD45/SSC and CD34/CD45 dot plots.

"If you are using ProCount to enumerate CD34+ cells in (even fresh)
marrow
samples, I would advise you to stop doing so. This kit was developed for
the enumeration of CD34+ cells in fresh PB and apheresis samples only.
Even in these limited circumstances, the automated software that
acquires/analyses these samples will sometimes 'flag' them, especially if
there are debris/platelet aggregates in the smaple. This usually
requires a
manual re-acquisition and analysis of the sample and even then analysis
may
still be problematic.
I know that it's not recommended to use TruCount tubes for BM. Of course
BM is more complex to analyse than PB but in my opinion with sufficient
routine it may not be problem to analyse. We don't use automated
software.

"This product is not recommended for use on
post-thawed samples (PB, CB, marrow, etc) because it does not include a
viability dye (only a nucleic acid dye for 'gating' nucleated cells)."
In our studies of recovery of viable CD34+ cells in cord blood samples
using the single platform ISHAGE protocol, that contains the viability
dye
7-AAD, we have noted a wide range of viable CD34+ cell recoveries,
ranging
from less than 50% to over 85%.  While there may be a variety of other
factors that determine recovery, methods of collection, time between
collection and processing/storage, and the mode of transport used to get
the samples from the collection point to the processing laboratory are no
doubt important factors. "
I agree, our method does not include viability stain but it can be done
separately. Because usually the fresh PB or PBSC samples have only very
small dead cell population (1-5% in my experience)  I think it's not
very important to count with it. In the case of thawed samples there is
another situation.
Yesterday before I made viability stain on two thawed BM MNC samples and
the viability was only about 50% so I think there is good correlation
with the findings that the CD34 pos. cell number decreased to the half
of the original fresh samples. If I understood right our haematologist
the goal of these post-thawed measurements is only for the controlling
purposes.

Thanks again,

Pal Jakso

University of Pecs
Faculty of Medicine
Dept. of Pathology
7643, Hungary
12. Szigeti str.



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