Find out more about why it is best to store cord blood using the volume reduction method

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Why do we choose to store volume reduced blood instead of whole blood?

The first reason is that it’s the industry standard in the UK, and globally. Both the NHS Cord Blood Bank and the Anthony Nolan Trust store volume reduced samples, as do the majority of public and private banks around the world. Smart Cells use processing technologies similar to those employed by many public banks. Volume reduction prior to freezing using the methodology we use, specifically preserves the all-important stem cells.


The second reason is that it’s safer. The freezing process used to preserve the stem cells in the sample damages the red blood cells, which means there’s a lot of debris and free haemoglobin in the sample when it’s thawed. In turn this can result in post-transplant complications. The volume reduction method reduces the red blood cell content.

Non volume reduced cord blood must undergo a washing step before clinical use and this can lead to loss of stem cells therefore red cell reduced units are favoured.

The reason why red blood cells are dangerous to patients is that they tend not to survive the freezing and thawing process. Red blood cells undergo “lysis” during cryopreservation, a rupture of the cell membrane that spills the cell’s contents, which include the haemoglobin and empty membrane sacks called red cell ”ghosts”. These lysed red cell elements can cause complications for patients including kidney, cardiac and respiratory problems at the time of transplant.

As the volume reduced method reduces the red blood cell content, this has the added benefit of minimizing reactions in the patient due to blood type incompatibility if the sample is being used for a brother or a sister.

Volume reduced blood v’s whole blood
Volume Reduced BloodAn example of a sample being processed using our volume reduction method

What do the experts think?

“Our processing depletes red cells (not totally though) and plasma to retain the so called “buffy coat” fraction that is rich in mononuclear cells. This means we are retaining the critical cells with proliferative capacity.

It is misleading for a whole blood storage company to say that the volume reduced method will only ever be useful in the treatment of haematological conditions. The volume reduced sample is just as likely to be useful in regenerative medicine in the future as whole blood. However when it comes to clinical use, red cell depleted products are acknowledged widely to be preferable thus the volume reduced method has the advantage.

The assertion by whole blood companies that volume is the critical factor is irrelevant – it is the progenitor/stem cell count that matters. For example, sometimes transplants in adults take place with single volume reduced cord blood units because the cell count is high enough. If it is not sufficient, two units can be used – this is not volume dependant. Volume reduced cord blood is used clinically to regenerate an entire haematopoietic system in individuals who have had high dose chemotherapy and also possibly total body irradiation so the product has to work or the results are catastrophic. Furthermore, when thinking about future innovative therapies such as regenerative medicine – for example in the treatment of stroke, cardiac disease or cerebral palsy– as yet we cannot be sure what doses of product will be optimal”

Dr. Ann Smith - Smart Cells Scientific Director

Dr. Ann Smith - Smart Cells Scientific Director

“Cord blood units that have not had their red cells removed are more difficult to use for patients. When the frozen unit is thawed, the red cells undergo lysis and break apart. The medical literature reports serious and life-threatening reactions when these products are infused without any dilution or wash. The current recommendation from the National Marrow Donor Program (Be The Match) is NOT to infuse units holding red cells as they are, but to wash or at least dilute them.

Washing cord blood units that hold red cells after they have been thawed is technically challenging. The free hemoglobin and the cellular debris released from the lysed (broken) red cells makes it difficult for laboratory scientists to see the demarcation between the nucleated stem cells that they want to keep versus the residual “supernatant” to be removed. The separation of different cell types becomes more difficult than it was in the pre-freezing cord blood unit, leading to some loss of desirable cells. In addition, post-thaw tests of cord blood potency with the Colony-Forming-Unit (CFU) assay may be difficult to interpret.

In summary, given the problems with handling cord blood units that hold red cells, both in the laboratory and in the patient care setting, the current industry standard is for most cord blood banks to perform partial depletion of RBC and removal of plasma before cryopreservation. In addition, those public cord blood banks that have been licensed by the FDA all use a system to deplete RBCs and plasma.”

Andromachi Scaradavou MD - Medical Director of the New York Blood Center's National Cord Blood Program

Andromachi Scaradavou MD - Medical Director of the New York Blood Center's National Cord Blood Program

Why store volume reduced?

Volume reduced blood v’s whole blood

Concentrated samples are more acceptable to clinical teams.

Plasma contains proteins, but no stem cells and a portion is retained following volume reduction as this helps the freezing process.

Volume reduction depletes the volume of red cells in samples. Red blood cells tend not to survive the freezing and thawing process and split to make red cell debris. Lower risk of infusion complications for patient which is preferred by clinical teams. They are not believed to help during transplant. (1, 2)

Less red cell debris which minimises incompatibilities when stem cells are being used for a sibling.

Growth factors vital for any form of transplant are retained in volume reduced samples.

Important cells are retained that would be useful for transplant for blood/marrow cancers and regenerative medicine. These include HSCs, MSCs and possibly other cell types such as VSEL cells

The regulatory and accreditation bodies recommend volume reduction with red cell depletion

1. The HTA advises that red cell depletion is important for transplant: https://www.hta.gov.uk/guidance-public/cord-blood-banking-guide-parents/cord-blood-banking-faqs/after-collection
2. The preference of clinical establishments is not to have to wash cord blood units as this can lead to loss of stem cells therefore red cell reduced units are favoured.

The Foundation for the Accreditation of Cellular Therapy and the Joint Accreditation Committee – ISCT and EBMT standards (JACIE) 7th Edition state:

“B7.6.3.1 Cord blood units that have not been red cell reduced prior to cryopreservation shall be washed prior to administration.


For cord blood units, the NMDP requires washing of red cell replete CB units due to unexpected adverse events”.

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