Re: Use of CD34+ internal controls

From: D. Robert Sutherland (rob.sutherland@utoronto.ca)
Date: Mon Dec 03 2001 - 11:59:39 EST


Hello Emanuel,

You have touched on a very tricky issue here.  There have been several
attempts to generate stabilised CD34+ cells for Quality Control and
Laboratory
Proficiency testing schemes.  Additionally, it is desirable to have at
hand, a product that contains a known concentration of CD34+ cells that
can be
used as a 'process control' for the single platform methodology you are
using.

We have evaluated many different products over the last few years and
have yet
to find the 'perfect solution' for these problems. Clearly, it is
verydifficult
to obtain large volumes of 'normal' mobilised blood that can be
stabilised and
stored for long periods of time for the sort of uses indicated above.
Thus,
Stem-Trol cells, based upon an engineered cell-line (KG1a) were
developed for this purpose, and included in the Beckman-Coulter
Stem-Kit.

As you indicated, while the CD45 and CD34 expression levels of the KG1a
cells have been engineered to mimic 'normal' CD34+ cells in mobilised PB

and apheresis products, their light scatter characterstics are quite
different, and the gating regions established for Stem-Trol must be
carefully altered to include all the stabilised KG1a cells therein. You
also indicated that you are practising the dark art of reverse pipetting

etc. as recommended.  I assume you used such techniques for pipetting
the Stem-Trol cells also. Again, as with the beads, you need to be
careful to fully suspend them prior to pipetting, without generating air

bubbles etc. Note however, that  Stem-Trol cells can withstand (and
indeed require)  much more vigorously vortexing than Flow Count beads.
This process should be performed immediatley prior to use, as they are
currently shipped in a conical vial and they 'pellet' quite rapidly .

You may have received a 'bad' batch of Stem-Trol cells, or you or one
of your colleagues may have inadvertently 'altered' the concentration of

the Stem-Trol by a failing to re-suspend them properly on an earlier
occasion. Of course, if an aliquot has been removed from an improperly
suspended sample, the assayed cell concentration is permanently altered.

I suggest you obtain another batch of Stem-Trol and try again.

Although we regularly 'run' Stem-Trol as a control, our day-to-day
samples are 'internally' controlled by assessing (as you also do) the
WBC count on all blood and apheresis samples. In that way,  we can
compare the absolute CD45+ cell count with the absolute leukcoyte count
from the hematolgy analyser.  Analysis of our results over hundreds of
samples shows that this is an extremely effective way of demonstrating
that the flow assay is working well.  This situation only pertains to
fresh blood and apheresis samples of course. Samples held overnight
prior to processing sometimes show differences between the absolute WBC
and the absolute CD45+ cell counts.  Presumably these differences are
due to loss of neutrophils, platelet aggregate formation and other
metaphysical side effects.  However, the absolute CD34+ cell counts
(derived by 'single platform' Stem-Kit protocols)  on such samples
change very little between 'fresh' and 'overnight' storage (assuming
appropriate dilution and storage conditions are observed). This
reinforces our view that single platform analysis represents the most
accurate manner in which to enumerate CD34+ cells (regardless of sample
condition).

I hope this helps.

Cheers,

Rob Sutherland
University Health Network,
Toronto




Emanuel Raniolo wrote:

> Hi all
>
> Our standard method for CD34 enumeration is a dual platform ISHAGE
gated
> (wash) method.
> In order to establish and validate a single platform (no wash) ISHAGE
method
> in the laboratory, it would be nice to be able to run an internal
control.
>
> I have used Beckman-Coulter's commercial Stem-Trol control cells for
this
> purpose, but have been unable to recover the stated assayed
concentration.
> In fact I my determinations are consistently higher than the allowable
+/-
> 15% range.
>
> Apart from some difficulties in gating placement, as these cells
display
> increased forward and side light scatter characteristics to normal
human
> haematopoetic precursors, I cannot see why my results are too high
(around
> 40% above the stated concentration). I practice reverse pipetting, and
mix
> the fluorospheres adequately prior to dispensing.  Single vs dual
platform
> comparisons for peripheral blood demonstrate a small positive bias in
favour
> of the single platform method, whereas results are identical for
apheresis
> product. In addition, the absolute CD45+ count is in general agreement
with
> the analyser WBC count.
>
> I would like to ask:
> What is the group experience with the use of internal controls for
CD34
> enumeration, and in particular with Stem-Trol cells?
> Is the stated Stem-Trol assayed concentration and range reflective of
common
> experience?
> Are internal CD34+ controls regularly utilised in routine practice?
> What alternative sources are available?
>
> Thanks
>
> Emanuel Raniolo
> IMVS Laboratories
> The Queen Elizabeth Hospital
> Department of Haematology
> Cell Analysis and Cryopreservation Laboratory
> Adelaide, South Australia.



This archive was generated by hypermail 2b29 : Sun Jan 05 2003 - 19:01:42 EST