Newsletter - July 2015

July is Cord Blood Awareness month

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ClinImmune & CariCord:
A Public/Private Cord Blood Partnership

U. Colorado Anschutz Medical Campus aerial view at sunset

ClinImmune, led by Brian Freed, PhD, has teamed up with CariCord, led by Calvin Cole. Launched in 2014, this partnership recognizes the growing number of evolving medical applications for both publicly donated and privately stored cord blood stem cells. Parents now have one cord blood bank that both accepts public donations, as well as provides family storage, and develops regenerative medicine therapies, all within a highly accredited and FDA licensed facility.

ClinImmune Labs is an academic-based biotechnology company that operates the public cord blood bank at the University Of Colorado School Of Medicine. Its location on the school's Anschutz Medical Campus in Aurora puts ClinImmune in close proximity to two hospitals performing stem cell transplants (University of Colorado Health and Children's Hospital Colorado).

ClinImmune is also a national provider of cell analysis such as flow cytometry and immunology testing such as solid organ and stem cell pre- and post-transplantation HLA typing for both research and clinical applications. It holds accreditations from the American Society for Histocompatibility and Immunogenetics (ASHI), the College of American Pathologists (CAP), the United Network for Organ Sharing (UNOS), the American Association of Blood Banks (AABB), and the Foundation for the Accreditation of Cellular Therapy (FACT).

Jonathan Gutman, MD, co-medical director of ClinImmune

ClinImmune was among the first cord blood banks to recognize that size matters in stem cell transplants: transplant physicians mainly want units with large numbers of stem cells. ClinImmune has achieved financial stability by adopting a high storage threshold in their pubic bank. Jonathan Gutman, MD, transplant oncologist at University of Colorado Health and co-medical director of the cord blood bank, says that his program uses cord blood in 60% of their transplant cases. Cumulative over the past two decades, ClinImmune has stored more than 8,500 donated cord blood units at its public bank, leading to more than 725 transplants at 150 different locations around the world.

Brian Freed, PhD, CEO of ClinImmune

Under the leadership of Brian Freed, PHD, ClinImmune was the second of only five public cord blood banks to attain a coveted Biologics License Applications (BLA license) from the FDA, a status which certifies that their cell therapy products have met the same level of quality and reproducibility as the preparation of pharmaceutical drugs. This FDA standard was to become legally binding on all US public cord blood banks in 2012, but as yet only five banks have met this requirement.

While some public cord blood banks have argued that the BLA license is too costly and ill-suited to the nature of stem cell transplants, ClinImmune believes that FDA licensure has benefited their donation program in numerous ways: participating hospitals no longer have to manage oversight of donation sites, informed consent is kept simple, all transfers of public cord blood units must have temperature monitoring, pre-storage family health screening is so thorough that there is no need for additional tests before release for transplant, cord blood unit labeling and purity testing are standardized, post thaw quality control is also standardized, and there is complete documentation and validation of all steps and components. Since 2012, ClinImmune has stored 650 cord blood units under its license and released 17, a respectable release rate of 2.6%.

Calvin Cole, CEO of CariCord

CariCord is the family banking side of ClinImmune, under the leadership of Calvin Cole. Family storage can provide cord blood for sibling transplants, which outperform both unrelated cord blood and bone marrow transplants for long-term survival. Ongoing clinical research is taking place on the treatment of neurologic disorders such as encephalopathy, cerebral palsy, and autism with stem cells from the baby's umbilical cord that were reserved for the family. Finally, family storage can provide raw material for other future regenerative medicine applications.

Ratan Bhardwaj, MD PhD, medical director of CariCord

Global medical director of CariCord, pediatric neurosurgeon Ratan Bhardwaj, MD PhD, notes that CariCord is an "evolutionary model in biological banking" because they are the first private biobank that is teamed up with an FDA licensed public biobank. Describing the collaboration between ClinImmune and CariCord, Bhardwaj coined the phrase:

"Curing Today, Innovating for Tomorrow"

Going forward, ClinImmune and CariCord are moving into a new 112,000 square foot bioengineering facility on the Anschutz Medical Campus of the University of Colorado. The new lab space houses four large cGMP class clean rooms that will enable them to develop cell therapy products that meet pharmaceutical standards.

One of the first cell therapies planned from the new facility is a partnership between the University of Colorado School of Medicine, CariCord, and CellResearch Corp. out of Singapore that will use stem cells harvested from the lining of the umbilical cord to heal diabetic wounds.

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2015 Reauthorization
Stem Cell Therapeutic and Research Act

Dr. Joanne Kurtzberg testifying in Congress June 2015

Since the passage of the Stem Cell Therapeutic and Research Act of 2005, the U.S. federal government has subsidized a national network of public cord blood banks. With this support, the U.S. inventory of unrelated donor cord blood units has increased to over 200,000. These are available to any patient in any nation who needs an unrelated donor for a transplant of blood-forming (hematopoietic) stem cells.

The legislation also supports the National Marrow Donor Program (NMDP), the Be The Match® registry of donors, coordinating centers for cord blood and adult donors, and an outcomes monitoring program at the Center for International Blood and Marrow Transplant Research (CIBMTR).

This legislation is up for "reauthorization" again this year.

Last month, Congressional Representatives Chris Smith and Doris Matsui, along with David Jolly and Chaka Fattah, introduced the Stem Cell Therapeutic and Research Reauthorization Act of 2015. The reauthorization bill provides five additional years of funding for the US national network of cord blood banks and for the associated registry, patient aide programs, and outcomes monitoring.

As President of the Cord Blood Association (CBA), one of my top priorities is to educate policymakers about cord blood research and transplantation and to advocate for passage of this important legislation.

Cord blood transplantation is used in adult and pediatric patients with leukemia and other blood cancers, bone marrow failure, inherited immunodeficiency syndromes, hemoglobinopathies like sickle cell anemia and thalassemia, and some inherited metabolic diseases. The latest research shows that cord blood transplantation also holds promise for treatment of patients with autism, traumatic brain injury, stroke and cerebral palsy.

CBA is an international non-profit organization that promotes public and private cord blood banking and the use of umbilical cord blood and related tissues for disease treatment and regenerative therapies. Our members include public and private cord blood banks, as well as health care providers in the cord blood community and their patients. Members are dedicated to promoting the work of the cord blood community, saving human lives, changing medicine and improving domestic and international policy.

Both CBA and NMDP are urging the U.S. Congress to pass the Stem Cell Therapeutic and Research Reauthorization Act of 2015. The original bill was spearheaded by Senator Orrin Hatch and former Senator Christopher Dodd along with Representatives Smith, Matsui and the late Bill Young. The 2005 law created the National Cord Blood Inventory (NCBI) program and the C.W. Bill Young Cell Transplantation Program and was reauthorized by Congress for five additional years in 2010. Since that five year period will conclude on September 30, 2015, these programs need to be reauthorized, once again, by Congress this year.

Lobbying for Reauthorization

On behalf of CBA, I recently met with key congressional leaders in the House and the Senate to urge support for the reauthorization legislation. During these meetings, I discussed the tremendous progress made in the field of cord blood transplantation as well as the challenges facing public cord blood banks from onerous federal licensure and contracting requirements. As a result of these meetings, several House Members cosponsored H.R. 2820. I expect similar levels of support when the Senate companion bill is introduced within the next few months, with sponsorship by Senators Orrin Hatch of Utah, Jack Reed of Rhode Island, Richard Burr of North Carolina and Al Franken of Minnesota.

The day after my Capitol Hill visits, the Energy and Commerce Health Subcommittee held a hearing on H.R. 2820. This subcommittee has jurisdiction over cord blood regulation, biomedical research, the Food and Drug Administration (FDA), and the Health Resources and Services Administration (HRSA). Witnesses in support of the bill included Dr. Jeff Chell, CEO of NMDP, and me on behalf of the CBA. In addition to challenges, we discussed how to encourage more expectant mothers to donate their cord blood, methods for cord blood collection and storage, the definition of a high-quality cord blood unit, cord blood therapies currently available to patients, and research underway to develop future treatments for other diseases.

Also of note, CBA and NMDP were successful in having a provision added to the annual federal funding bill in the House that would require the FDA to create a public/private working group to make recommendations for updated regulation of public cord blood banks.

Finally, along with representatives from the five public cord blood banks that hold FDA licenses and the NMDP, I participated in a recent meeting with officials from FDA and HRSA to discuss our collective experiences and practical concerns about banking and transplantation. Encouragingly, the meeting resulted in FDA officials offering to work with us on possible solutions.

Call to Action

While CBA has had a successful few weeks in Washington, more work needs to be done. How can you help?
CBA icon First, ask your U.S. Representative to cosponsor H.R. 2820 and tell him or her that the bill needs to be passed this year. Currently, the legislation has a total of eight cosponsors.
CBA icon Second, ask your U.S. Representative to join the Congressional Caucus to Cure Blood Cancers and Other Blood Disorders. This Caucus educates House members and their staff about bone marrow and cord blood transplants and helps to promote our efforts.
CBA icon Third, call or write your U.S. Senator to express your support for their efforts to reauthorize the legislation.

Dr. Joanne Kurtzberg is an internationally reknowned expert in pediatric hematology and oncology, pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation, and novel applications of cord blood in the merging fields of cellular therapies and regenerative medicine. Her current titles at Duke University Medical Center include Director of the Pediatric Blood and Marrow Transplant Program, Chief Scientific and Medical Officer at the Robertson Clinical and Translational Cell Therapy Program, Director of the Carolinas Cord Blood Bank, and co-Director of the Stem Cell Laboratory. The remainder of her extensive biography can be found here.

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TotiCyteTM - the next generation
of cord blood processing technology

TotiCyte comparison table

The most important factors in determining a successful stem cell transplant are human leukocyte antigen (HLA) match and number of living (viable) cells available for treatment.

HLA is the finger print equivalent to see if the donor matches the patient. If they do not, then game over. However, if there is a good enough match, then 25 million total nucleated cells (TNC) per kg of bodyweight are required to give the patient the best chance of a successful stem cell transplant.

Many public cord blood banks apply a very high TNC threshold before they will store a cord blood unit for possible transplant use. Thresholds between 140 and 200 billion TNC increase the probability that the samples they process will be therapeutically useful.

But few babies have a large enough volume of cord blood to reach this threshold. In the end, 80-90% of cord blood donations go to waste.

Volume reduction technologies

The leading methods of processng cord blood for storage employ a volume reduction step that aims to remove some of the non-useful red blood cell fraction and the plasma. For example, a starting volume of 100ml will be reduced to 25ml for final storage.

However, all volume reduction technologies result in stem cell losses approaching up to 40% (1), and in some instances, the almost total loss of potentially important low abundance cells (2). Significant levels of red blood cells remain, which can be up to 30% of the starting concentration (3).

TotiCyteTM - a new paradigm in cell recovery

Cells4Life has developed TotiCyteTM, a processing method which selectively removes the red blood cells in cord blood and yields:

  • * over 95% recovery of the white cell fraction,
  • * 99.5% removal of the red cells,
  • * obviates the need for washing to remove DMSO and red cells, and
  • * exceptionally high post thaw viable cell recovery

TotiCyteTM is a mixture of compounds already commonly used in blood product processing. When added to cord blood, gravity causes the red cells to selectively sediment within 30 minutes and the white cells remain in solution. These white cells can be easily separated from the sedimented red cells, and the important white cells can then be concentrated by gentle centrifugation into a small volume containing less than 0.5% of the original red cell content. Addition of a small amount of DMSO for cryogenic storage and controlled freezing using standard procedures then completes this simple process.

Post-thaw recovery

One of the most exciting features of TotiCyteTM is improved post-thaw recovery. When cord blood stem cells are cryopreserved and then thawed for therapy, large cell losses occur during thawing. With TotiCyteTM, the viable cell recovery post-thaw is markedly increased. Approximately 76% of the CD34+ remains viable, whereas post-thaw viability with the current leading separation methodology can be as low as 32% in some instances (4).

Entire white cell fraction

TotiCyteTM allows almost the entire white cell fraction to be isolated and/or concentrated, with only modest, if any, loss of any cell type thus far examined. Other processing methods frequently result in the loss of the megakaryocyte-like (CD45+CD61+) cells and/or MNC-like (CD45+CD34+) cells.

After processing with TotiCyteTM, we have identified a significant population of cells that express both Oct4 and Nanog, indicating that very early progenitor cells are maintained by our method. By comparison, the so-called Very Small Embryonic Like stem cells (VSELs) are lost in processing methods that employ centrifugal first stage separation (2).

Impact for the public banking model

TotiCyteTM will positively impact the value chain of public cord blood banks in several ways:

TotiCyte icon Cord blood processing with TotiCyteTM will be cheaper than current methods.
TotiCyte icon Fewer donations will be wasted because the higher cell yield enables many more collections to meet the threshold for storage.
TotiCyte icon More high TNC cord blood units in storage means more units that are desirable to be purchased for transplant.
TotiCyte icon Building the inventory of high TNC cord blood units also means that heavier patients can be transplanted, moving the therapeutic use segment from primarily children to adults.
TotiCyte icon TotiCyteTM's high TNC yield should enable only one cord blood unit to be used for larger adults, obviating the need for very expensive double cord blood transplants.

In summary, our results show that TotiCyteTM can deliver a larger number of viable cells for therapeutic use and more stem cell types than any other volume reduction technology.

The public banking business model suffers from high wastage of donations and under-distribution of stored cord blood. TotiCyteTM will increase public banking profitability both by reducing the number of donations that are discarded and by increasing the quality / marketability of the stored cord blood units.

Cells4Life logo Cells4Life is a science-led organisation dedicated to delivering the best stem cell storage service in the world. Cells4Life stores more UK stem cell samples than any other private bank. We adhere to rigorous collection, storage, quality and safety procedures, and our customers receive support from a highly experienced team of doctors, scientists and specialists. For more inofrmation about TotiCyte, contact Dr. Jeff Drew.

References:
  1. Lapierre, V., Pellegrini, N.,Bardey, I., Malugani, C., Saas, P., Garnach, F., Racadot, E., Maddens, S., & Schillinger, F.
    Cord blood volume reduction using an automated system (Sepax) vs. a semi-automated system (Optipress II) and a manual method (hydroxyethyl starch sedimentation) for routine cord blood banking: a comparative study.
    Cytotherapy. 2007; 9(2):165-9. PMID: 17453968
  2. Bhartiya, D., Shaikh, A., Nagvenkar, P., Kasiviswanathan, S., Pethe, P., Pawani, H., Mohanty, S., Rao, A., Zaveri, K. & Hinduja, I. 2012.
    Very Small Embryonic-Like Stem Cells with Maximum Regenerative Potential Get Discarded During Cord Blood Banking and Bone Marrow Processing for Autologous Stem Cell Therapy
    Stem Cells and Development. 2012; 21(1):1-6. doi:10.1089/scd.2011.0311
  3. Basford, C., Forraz, N., Habibollah, S., Hanger, K. & McGuckin, C.
    The Cord Blood Separation League Table: a Comparison of the Major Clinical Grade Harvesting Techniques for Cord Blood Stem Cells
    International Journal of Stem Cells. 2010; 3(1):32-45. PMCID: PMC4022688
  4. Henderson, C., Wofford, J., Fortune, K. & Regan, D.
    Evaluation of Processing Technologies for Umbilical Cord Blood.
    ISCT Poster, 2010 annual meeting, Philadelphia, USA