Development of potency assays for the evaluation of cord blood

by Alexey Bersenev on May 4, 2011 · 1 comment

in cell product, clinical lab, cord blood, hematopoietic

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The guidelines for umbilical cord blood (UCB) potency assays development just released in online version of Cytotherapy. Because it is very important and because many of you have no access to this journal, I’d summarize the most important points of the guidelines below.

Significance:

Fifteen to 24% of patients receiving UCBTx do not engraft. One potential cause of engraftment failure is a loss of reconstituting hematopoietic stem cell potency that may have occurred at some stage during UCB collection, processing, storage, shipment and infusion. The best measure of potency is still unclear and current assays are limited by a lack of consistency among laboratories performing the assays.

Definitions:

Potency is defined as the specific capacity of a cellular product to affect a given result.

The FDA Guidance for Industry defines UCB potency by parameters measured on the UCB after processing but prior to cryopreservation

Current assays indicate potency:
required:

total nucleated cell count (TNC);
cell viability;
CD34 analysis

additional (not required):

red blood cell count;
white blood cell count differential;
colony-forming units (CFU) assay

Current problems and flaws:

  • … the methodologies and assays can yield highly variable results in interlaboratory testing settings on identical material.
  • A lack of consensus regarding which potency assays to perform remains an issue within the UCB banking and transplantation community.
  • Neither of these (current) approaches directly measures the quantity or quality of the hematopoietic stem cells withing the stored UCB product.
  • Results of proficiency testing program suggest that more robust and consistent assays are required to allow UCB banks and transplant centers to obtain comparable results for potency.

Unresolved questions:

  • What the next generation potency assay would be?
  • Should potency be assessed only prior cryopreservation or post-cryopreservation also?
  • How many and what volume of satellite samples should be?
  • What clinical lab should validate in post-thawed cell product before transplant?
  • What is the best predictor of stem cell engraftment which can be measured in potency assay?

A request for developers:

  • standardized methodologies
  • reproducibility with limited variability between testing sites
  • automated testing outputs (objectivity)
  • high throughput for UCB banks
  • rapid turnaround time
  • single sample test for transplant centers.

Finally, NMDP Cord Blood Bank Network can assist any stage of assay development, providing cord blood samples for research, contract services and consultancy.

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If you would like to get a .pdf version of this guidelines, please contact us.

{ 1 comment… read it below or add one }

Alex Moffett May 6, 2011 at 9:57 am

One of our observations concerning the current protocols in UCB banking is that it is lacking qualitative elucidation of the samples and evidence based confirmation of the true therapeutic potential of the cellular composition in the unit being banked.

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