Not all umbilical cord tissue banks are the same: Does storage method compromise parent access?

Awareness and popularity of cord blood banking has increased across Asia, the Americas, Europe and Australia since the first cord blood transplant in 1988 [1]. Cord blood is a rich source of haematopoietic stem cells (HSC). These specialised cells give rise to all other blood cells and are currently used to treat a range of blood disorders and immune system diseases including leukaemia, lymphoma, anaemia and other blood disorders [2, 3].

Most parents and grandparents exploring the idea of cord blood banking are not aware of the full potential of the umbilical cord tissue. In the last 10 years scientists have realised that the umbilical cord represents one of the most concentrated sources of Mesenchymal Stem Cells (MSC) [4]. Additionally, MSC derived from the umbilical cord are considered to be neonatal and exhibit significant physiological and biological advantages over MSC sourced from adults [5, 6].

MSC have the ability to  differentiate into cells of  bone, cartilage, fat, muscle, tendons and ligaments (Figure 1) [7-9]. Unlike cord blood HSCs, which are mainly used as therapy for rare blood diseases, MSCs can contribute to therapies for osteoarthritis and sports injuries, problems which almost everyone experiences at some point in life. Due to their self-renewal ability, expansion potential, immunomodulation properties, and engraftment capacity, MSCs represent a promising candidate for cell based treatment of an array of medical conditions, such as, Alzheimer’s, cerebral palsy, Parkinson’s disease, psoriasis, rheumatoid arthritis, spinal cord injury,  and stroke [9-21].

A closer examination of the tissue composing the umbilical cord reveals that the highest concentration of MSC is in the perivascular space surrounding the three blood vessels (Figure 2) [22]. A study at the University of Pittsburgh published in 2009 found that approximately 88% of all MSCs in the umbilical cord tissue are found in the perivascular tissue [22].

Despite the growing scientific appreciation of umbilical cord MSC as future therapeutic agents, the general public is still predominantly unaware that the optimal source of MSC is the umbilical cord. There is also a lack of education as to the best method to process and store these vital cells to ensure future access to MSC for therapy.

When parents consider the ability to access MSC from their stored cord tissue, the steps involved are (1) whether their bank is storing a product that holds a high concentration of MSC, (2) whether the MSC will be viable upon thaw, and (3) whether the bank has licensed technology to provide these services.

The Parent’s Guide to Cord Blood Foundation conducted a survey of family cord blood banks during the summer of 2015 [23]. At that time exactly half of the companies that operate their own laboratory were storing cord tissue in addition to cord blood. In response to the survey, about half of the companies that stored cord tissue admitted that they are storing whole or minced tissue, and not isolating MSC prior to storage [24]. In other words, storage of a tissue product, and not a cellular product, is the most common practice among banks that offer cord tissue storage to parents.

Cryosite, following patented protocols from Tissue Regeneration Therapeutics (TRT), isolates and stores the blood vessels of the umbilical cord, which includes the vital perivascular zone. Cryosite initiated a research project to compare the retrieval of MSC with their storage method versus the retrieval of MSC from whole cord tissue. The study consisted of a pairwise comparison of 9 umbilical cords which were processed by both methods. The number of viable nucleated cells isolated per gram of cord tissue was on average 0.44 million from the perivascular zone versus 0.17 million from whole cord tissue. This represents an average increase of 2.73 fold in viable cell density achieved by physically isolating perivascular zone tissue, a result that is strongly statistically significant (p-value of ≤ 0.01).

It is also important that the method used to cryopreserve cord tissue will allow viable MSC to be isolated and expanded when the product is thawed at a clinic [25]. Additional research by Cryosite tested 94 umbilical cords to determine if viable MSC could be retrieved from frozen perivascular tissue. All of the samples were successfully thawed and cultured to yield expanded MSC.

Finally, parents should be aware that in the event that they submit a request to release cord tissue or to isolate MSCs for therapy, they may face unforeseen difficulties if their storage bank did not have an appropriate license. Parents who are shopping for cord tissue storage may not realise that they need to be concerned about patent law. But in fact, those companies that discovered and developed umbilical cord tissue MSC sources (i.e. the perivascular space [26] and the sub-amniotic space [27]) own patents on methods of processing, preserving, and expanding these vital cells. It is a good idea for parents to ask a prospective cord tissue bank if they have licensed access to the technology needed to isolate and expand cells for therapeutic application. Therapeutic centres that one day might use cord tissue derived MSC may face legal issues if they accept MSC from cord tissue banks that have infringed patents. Clinical trials could also exclude cells that have not been collected by a licensed method.

In conclusion, parents and grandparents should be educated about all the factors that will influence their ability to access therapy with MSC from cord tissue, so that if they purchase this service they are making a fully informed decision.

Dr Michael Sivell leads the Cellular Therapies Research & Development team at Cryosite, Australia's pioneer in family cord blood and tissue banking headquartered in Sydney, Australia. Driven by a strong belief that stem cell based therapeutics have the potential to change lives, Michael has pursued research projects that attempt to optimise the cryopreservation of neonatal stem cells so that these valuable cells can be exploited to their full potential in future times of need. Michael, a PhD graduate of the University of Sydney and University Medal recipient from the University of Technology, has previously worked in the stem cell regenerative medicine field developing processing techniques required for the isolation and propagation of adult stems cells from adipose tissue. Cryosite was the first family cord blood bank in Australia, and offers parents the patented cord tissue storage method developed by Tissue Regeneration Therapeutics (TRT). Cryosite also provides parents with a tissue viability guarantee. Listed on the Australian Stock Exchange (CTE), they are the only publicly listed cord blood and tissue bank in Australia, with their financial position always accessible to parents.

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