According to Luc Noël, MD of the World Health Organization, transplantation has extended the lifespan of hundreds of thousands of patients worldwide and enhanced their quality of life and has become the standard of care for many patients, and should no longer be restricted to affluent countries or individuals. The curative potential of this therapy will only increase, thanks to the commitment and collaboration of researchers and physicians across the globe.
Haematopoietic stem cell transplants (HSCT) have been performed for more than 50 years and have been used to treat or cure more than 80 potentially life-threatening blood related diseases like leukaemia, lymphoma and bone marrow failures. To date, more than 1 million blood stem cell transplants have been performed, with more than one third using cord blood stem cells.
Cord blood stem cells have been used as a source of stem cells for transplantation for almost 30 years. It has been shown that cord blood stem cells are more immunologically tolerant, allowing transplantation without full HLA matching, providing access to transplantation therapies for patients lacking fully matched related or unrelated donors. Even in the mismatched setting, cord blood caused fewer incidences of graft-versus-host disease without losing leukaemia fighting activities. Banked cord blood is rapidly available, without donor attrition, with more than two decades of long-term stability in the cryopreserved state.
By 2013, private cord blood banks have released 530 samples for autologous transplants and 485 for allogeneic transplant.
Within the Cyro-Save group there have been 18 releases to date to centres such as Duke University North Carolina, USA, Kliniek Pediatrische Hematologie en Oncologie Frankfurt, Germany and Konderite Zurich, Switzerland. Fourteen of the 18 samples were released for autologous and sibling transplants, and four used in clinical trials for cerebral palsy. One sample was released in SA for diagnostic genetic testing for acute lymphocytic leukaemia.
Increasing awareness about stem cells
To date, nearly 800,000 cord blood samples are banked in public banks, and more than five million samples are stored in private banks.
Established in 2000, the CryoSave group has cryopreserved and stored more than 330 000 samples from over 30 countries on three continents, with processing and storage facilities in Geneva, Belgium, Netherlands, Portugal, UAE and South Africa.
Umbilical cord blood has enormous potential to treat many other medical conditions that currently have unmet needs
In addition to the use of banked cord blood as a source of donor cells for HSCT, cord blood is now emerging as a promising new cell therapy. Cord blood is not just a ‘‘bag of blood stem cells,’’ and newer therapies are leveraging the activities of monocytes and other cells in the mix.
Regeneration in the central nervous system
Umbilical cord blood contains a rich and diverse mixture of stem and progenitor cells that have the potential to generate a variety of cell types. It has been shown to induce regeneration in the central nervous system.
Autism Spectrum Disorder
In May this year, the CNN program Vital Signs featured a Duke University clinical trial evaluating the safety and feasibility of autologous cord blood infusion in young children with Autism Spectrum Disorder. The results, published on 5 April this year in the journal Stem Cells Translational Medicine, confirmed safety and feasibility and reported significant improvements in autism symptoms and social communication skills as observed on parent-report measures as well as clinician’s ratings of overall symptom severity and degree of improvement. A second phase clinical trial is expected to be completed in 2019.
The safety of autologous cord blood infusions in children with cerebral palsy and other acquired brain injuries have been demonstrated and when adequately dosed, significant improvement in motor function in young children with spastic cerebral palsy were observed.
While these results are preliminary, they create hope for cord blood-derived cellular therapies as novel treatments for diseases that cause life-long disabilities and currently have no curative options.
CryoSave is championing the first clinical trial to utilise two types of stem cells for the treatment of cerebral palsy. The clinical trial aims to demonstrate the safety and preliminary efficacy of sequential intravenous infusion of the ex vivo expanded mesenchymal stem cells (MSC) derived from cord tissue and cord blood stem cells. The study will use, for the first time in clinical research, autologous MSC derived from cryopreserved cord tissue. The clinical trial, sponsored by CryoSave, will be performed in collaboration with Professor Manuel Ramírez Orellana, the Principal Investigator, and Professor Luis Madero, the Clinical Supervisor from the University Hospital Niño Jesus in Madrid, Spain.
Modulating the immune system
Type 1 Diabetes Cord blood stem cells are particularly unique because they not only have the capacity to develop into other cell types, but are also immune tolerant – that is they are less likely to provoke an immune response. They also contain greater numbers of regulatory T-cells – a particular type of white blood cell that helps to keep the immune system in balance. This makes cord blood stem cells potentially useful for treating diseases where the immune system has ‘gone astray’ – such as type 1 diabetes.
In Australia, a pilot clinical trial called “Cord blood Reinfusion in Diabetes” (CoRD) seeks to prevent diabetes with cord blood. To be eligible, children must have their own cord blood in storage, have a relative with type 1 diabetes, and have antibodies which signal that their immune system is already attacking their insulin producing cells in the pancreas. Study participants will have their own cord blood reinfused and the hope is that a reinfusion of their cord blood stem cells will reset the immune systems of these children, before the auto-immune damage leads to a diagnosis of type 1 diabetes. This research is one of several potential avenues in which scientists hope that stem cells will help patients to preserve their insulin producing cells and thereby be cured of diabetes.
What will future be for cord tissue stem cell therapy?
As medical science continues its research into stem cells and their flexibility, the list of possible treatments grows. Many researchers consider the transplantation of mesenchymal stem cells (MSCs) to be the most effective tool for cell therapy, due to the simultaneous activation of multiple mechanisms (paracrine, trophic, immunomodulatory, and differentiation), affecting all stages of the regeneration of damaged tissues.
The ability of mesenchymal stem cells to differentiate into mesoderm- and non-mesoderm-derived tissues, their immunomodulatory effects, their availability, and their key role in maintaining and replenishing endogenous stem cell niches have rendered them one of the most heavily investigated and clinically tested type of stem cell.
The human umbilical cord is a source of MSCs that have a unique combination of prenatal and postnatal MSCs properties; no ethical problems with obtaining biomaterial; significant proliferative and differentiation potential; lack of tumorigenicity; karyotype stability; high immunomodulatory activity.
Currently, the FDA has registered dozens of clinical trials (phases 1–3) on the safety and efficacy of umbilical cord MSCs therapy for the treatment of socially significant diseases including acute myocardial infarction, cardiomyopathies, critical limb ischemia, bronchopulmonary dysplasia in infants, HIV infection, diabetes mellitus types I and II, both acute and chronic liver diseases, autoimmune hepatitis, cirrhosis of various etiologies, ulcerative colitis, severe aplastic anaemia, Alzheimer’s disease, systemic lupus erythematosus, rheumatoid arthritis, myelodysplastic syndrome, hereditary ataxia, spinal cord injury, ankylosing spondylitis, osteoarthritis, multiple sclerosis, Duchenne muscular dystrophy, acute and resistant to steroid therapy “graft versus host” reactions, and other diseases.
The results of clinical trials using umbilical cord MSCs are encouraging, particularly for treatment of autoimmune and endocrine diseases.
CryoSave, together with the University of Cologne, pioneered validated methods for cord tissue collection, viability testing, cryopreservation, and isolation of mesenchymal stem cells (MSC) from umbilical cord tissue, and were the first company in the world to offer this service to its customers.
Esperite’s (Swiss holding company of CryoSave) translational research and regenerative medicine division, is led by Dr. Marcin Jurga PhD, and between stem cell cryopreservation and existing and future regenerative medicine treatments, is primarily focused on allogeneic EVs and autologous applications of stem cells and have registered 5 international patents of mesenchymal derived extracellular vesicles biologic drugs and mesenchymal stem cell therapies. The group is sponsoring an international consortium of leading teams in EVs applications in Crohn’s disease (collaboration with Padua Hospital University, Department of Women’s and Children’s Health) and in drug-resistant epilepsy in children (collaboration with the Gesù Children’s Hospital in Rome and Mario Negri Institute for Pharmacological Research in Milan).
To quote Joanne Kurzberg in summary: “It is remarkable that a routinely discarded substance can save lives. While the potential of cord blood in HSCT is largely realized, it will continue to expand access to donors for patients of minority ancestries who need donors for HSCT for malignant and non-malignant diseases, such as sickle cell anaemia. More excitingly, I predict that the use of cord blood cells, in both autologous and allogeneic settings, as cellular therapies in the emerging field of regenerative medicine, currently in its infancy, will emerge as one of the major great advances in novel therapeutics in medicine over the next decade.”
Join CryoSave in educating patients on the procedures and benefits of storing cord blood and tissue to provide future resources for their own families and donors in need.
For more up to date information on new and local developments in stem cell storage visit www.cryo-save.co.za