Cord Blood Transplants Provide an Opportunity to Treat Blood Cancers

When a patient with a blood-related cancer needs a bone marrow transplant, there are four common donor sources: A matched related donor (a family member), a matched unrelated donor (from a donor database), a half-matched donor, or umbilical cord blood. The reason for this is that most patients with blood-related cancers were born with the genetic defect that triggered the cancer, they cannot use their own stem cells as a source for transplant. As with any approach, each has its pros and cons, but consensus has generally placed a matched sibling first, followed by a matched unrelated donor, with cord blood and half-matched donors reserved for patients without access to either of the first two options.

According to statistics only about one-quarter of the people who need an allogeneic (unrelated donor) transplant have a sibling who is a genetic match and able to donate stem cells. The other three-quarters need to find another donor for their transplant.

The test that’s used to identify appropriate donors is called HLA matching (human leukocyte antigen). HLAs are proteins that are present on most cells in your body. Your immune system uses HLAs to recognize which cells belong in your body. When using an adult donor, it’s important that the donor and the person undergoing the transplant have HLAs that match so the donor immune system doesn’t attack the patient’s normal tissues, a complication called graft-versus-host disease.

A person’s HLA type is inherited from their parents, which is why siblings offer the best chance of finding a match. People’s HLA type can be determined with a simple blood test or cheek swab. People of southern European, Asian, African, Hispanic, and Middle Eastern backgrounds tend to have more diverse HLA types. These types are less commonly found in adult volunteer donor registries. It can also be difficult for someone with a mixed background — for example, part Asian and part Hispanic — to find a donor who is a match. For them, cord blood transplants offer a good opportunity for a cure.

In the past 3 decades there have been more than 40,000 cord blood transplants performed internationally. These were mainly for leukemias, lymphomas and other blood-related disorders. Cord blood transplants offers a cure for blood related cancers in both children and adults.

Stem cell transplants with cord blood have been used to cure both children and adults with leukemia since the early 1990’s.

Why Cord blood for stem cell transplant may outperform a matched sibling donor:

A major benefit of cord blood is that the immune system of a newborn baby is not yet entirely developed. This means that the match that’s required between the cord blood stem cells and the person receiving them is less strict. Since umbilical cord stem cells are more “basic” than adult blood cells, they therefore need a lower level of matching than blood cells from an adult donor. Nevertheless, even though the cord blood immune system is very flexible, it can still develop into a healthy immune system. Cord blood cells are very good at combating cancer, this effect is called the graft-versus-leukemia and it can help prevent a person’s cancer from returning after their transplant.

The University of Colorado Cancer Center did an assessment of 190 patients getting cord-blood transplants versus 123 patients receiving transplants from the “gold standard” of matched sibling donors bone-marrow. Although the survival outcomes were the same between the two methods, considerably fewer complications were found in chronic graft-versus-host disease in patients receiving transplants from cord blood. The cord blood group also showed a slightly lower rate of relapse.

One challenge with cord blood cells is obtaining enough of these cells to perform a successful transplant, especially in adults.

To overcome this hurdle, double unit cord transplants from two different sources are transplanted.  The other alternative is to expand small samples of banked cord blood to the amount of stem cells needed for transplant.

All these above factors indicate that cord blood may even out-compete the gold standard of matched sibling donors.

Therefore, for people who don’t have a matched bone marrow or stem cell donor, a cord blood transplant may offer the best chance for being cured of blood cancer.

References:

  • Gale KB et al. 1997; Backtracking leukemia to birth: Proc Natl Acad Sci USA. 94(25):13950-4.
  • Janet D. Rowley 1998; Backtracking leukemia to birth: Nature Medicine 4:150-1.
  • Ballen KK, Verter F, Kurtzberg J 2015; Bone Marrow Transplantation 50(10):1271-8.
  • Filippo Milano, et al. 2016; Cord Blood Transplants Show Promise in Leukemia Treatment. NEJM 375:944-953.

What Is Regenerative Medicine?

Regenerative therapy is the healing or replacement of tissues or organs that have been damaged by disease, trauma, or congenital issues, as opposed to the age-old clinical approach that relies primarily on the treatment of symptoms. Four disciplines are used in regenerative therapy, i.e., tissue engineering, cellular therapies, medical devices and artificial organs.

The field of regenerative therapy is quite new and various combinations of the aforementioned methods can be used to treat patients. The field involves a combination of disciplines, for instance:  biology, chemistry, computer science, engineering, genetics, medicine, robotics, and other fields to find solutions. The ultimate goal of Regenerative Medicine is to find a way to cure previously untreatable injuries and diseases.

1. Tissue Engineering and Biomaterials

Tissue engineering is the application of biologically compatible scaffolds that are implanted in the body at the site where new tissue is to be formed. The scaffold might be in the geometric shape of the tissue that needs to be formed, the scaffold might attract cells or cells will be implanted and the outcome is new tissue in the shape desired.

2. Cellular Therapies

Stem cells are important for the body to repair itself and many millions of adult stem cells are found in every human. These cellular therapies involve the use of adult stem cells that are injected at the site of diseased or damaged tissue, where the rebuilding of the tissue is possible under the right stimuli. These adult cells can be collected from blood, fat, bone marrow, dental pulp, skeletal muscle, and other sources. Cord blood is one of the most unique and potent sources of stem cells currently in use.

3. Medical Devices and Artificial Organs

In cases where an organ fails, the main clinical approach is to transplant a substitute organ from a donor. One of the major challenges are the availability of donor organs and the requirement that the donor takes immunosuppression drugs—which have significant side effects and risks. A novel strategy that has emerged is the 3-D printing of organs. In this way, the stem cells that build the new organ are manipulated to form the tissue of the specific organ and these cells will populate a 3-D scaffold of the organ. These stem cells can be engineered from the same patient’s cells and thereby any organ rejection will be eliminated.

Studies have shown promising results in treating burns, heart disease, trauma and other diseases.

To quote the Biopharma Reporter:

“We are on track for a watershed year for approvals of new regenerative medicine and advanced therapies globally. Decisions are expected on 18 regenerative medicine products across 6 geographies, with 10 of these on products that have never been previously approved in any geography – meaning new product approvals could exceed the record of nine set in 2016.”

There are currently 2,600 clinical trials ongoing worldwide in this sector, of these 1,320 are industry-sponsored and an additional 1,328 non-industry sponsored. There are 243 trials in Phase 3, including 1158 industry-sponsored trials and 85 trials sponsored by academics, the government and other institutions. The late-stage products are being tested for instance in diabetic neuropathy, heart failure, rare genetic diseases, and neuromuscular diseases.

The biggest buzzword in the industry is “off-the-shelf” therapies, which are easily accessible. Therefore, as the field continues to grow, developers are seeking to work more closely with regulators to set improved standards. All these developments in the field of regenerative medicine across a broad scope of medical disciplines will ultimately aid in new solutions to expand and sustain optimal health and quality of life.

References

  • Arthur, R. (2021). ‘We are on track for a watershed year for approvals of new regenerative medicine and advanced therapies’. Retrieved 10 November 2021, from https://www.biopharma-reporter.com/Article/2021/09/01/We-are-on-track-for-a-watershed-year-for-approvals-of-new-regenerative-medicine-and-advanced-therapies
  • Ntege EH, et al. Advances in regenerative therapy: A review of the literature and future directions. Regen Ther. 2020 Jun; 14: 136–153.

A summary of COVID-19 Mesenchymal stem cell therapy to date

The COVID-19 pandemic is affecting everyone, some more than others. For many families, it means making changes to daily routines because of financial hardships. For others, it means raised anxiety in children and tension in parenting relationships. It can be difficult to cope with the “new normal”, since everything we are used to has changed, and there seems to be no end in sight to the pandemic.

A wide variety of medications are currently under investigation for the treatment of COVID-19. These medications include anti-viral, anti-malarial, and anti-inflammatory medications.

Almost all of these medications improve the recovery process and the life expectancy of patients but do not lead to definite repair of the lung damage caused by this disease. One of the most promising therapies to date is stem cell therapy, which could reduce inflammation but also restore the lung damage caused by COVID-19.

Mesenchymal stem cells (MSCs) are the stem cells that might be the most encouraging treatment for SARS-CoV-2 infections. The main factor in treating SARS-CoV-2 infection lies in the management of the cytokine storm in the lungs, therefore MSCs are suitable for this since their main mode of action is through their immunomodulatory, anti-inflammatory properties, as well as their ability to restore and remodel the lungs.

Since the start of the pandemic, more than 17 clinical trials evaluating the benefits of MSCs for the treatment of COVID-19 are underway. In previous years before the pandemic, the safety and efficacy of MSCs have been well established based on the completion of other clinical trials in lung diseases such as acute respiratory distress syndrome (ARDS) (Chen J, et al. 2020), bronchopulmonary dysplasia (Namba 2020), cardiovascular diseases (Kim et al. 2015), diabetes (Thakkar et al. 20150, and spinal cord injury (Xu and yang, 2019).

MSCs have been investigated as early as 2013 and 2015 for the treatment of ARDS and have shown the capacity to stimulate repair in the distal ends of the lungs.

In a comprehensive study of the clinical trials using MSCs for the treatment of ARDS, 2691 studies were reviewed. The MSCs were from various sources but were all allogeneic from either bone marrow, umbilical cord, menstrual blood, adipose tissue, or unreported sources. Overall, the patients showed better survival, no severe side effects. The patients also showed improved lung scans, lung functionality, and improved inflammatory marker levels.

All these studies concluded that ARDS patients showed low risk, reduced risk of death, and improvement in lung functionality using MSC treatment. The MSC treatment also eased the clinical symptoms leading to ARDS.

It is therefore believed that evidence suggests a favourable benefit of using MSC therapy for COVID‐19 patients. However, it is suggested that larger clinical trials that follow the same protocol should be used to standardise the treatment of ARDS.

Reference:
  • Mahendiratta S, et al., Stem cell therapy in COVID-19: Pooled evidence from SARS-CoV-2, SARS-CoV, MERS-CoV, and ARDS: A systematic review. Biomed Pharmacother. 2021 May; 137: 111300.

The Application of Umbilical Cord Stem Cells in the Treatment of Covid-19

We at CryoSave South Africa wish to assure all clients that we are structured to be fully operational during the Nationwide COVID-19 lockdown. Together with our
Support Services, we trust that we will be able to continue to provide you with an excellent service and keep you updated on recent developments in the field of stem cell research and therapy. As a CryoSave Client, you might be interested in the following information relating to the potential application of umbilical cord stem cells in the treatment of COVID-19.

After the initial outbreak, the Coronavirus, (COVID-19), has spread to more than 100 countries and infected any thousands of people. Coronaviruses (CoV) belong to a large family of viruses causing respiratory illnesses, ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). On March 11, the World Health Organization (WHO) upgraded the status of the COVID-19 outbreak from epidemic to pandemic. Epidemic refers to a sudden increase in the number of cases of a disease above what is normally expected.

Pandemic refers to an epidemic that has spread over several countries or continents, usually affecting a large number of people. The most effective preventative treatment against a pandemic is a vaccine. Antibiotics are not effective because COVID-19 is a viral infection and not bacterial. There are currently various vaccine and treatment options being investigated around the world. Some medications may have the potential to be effective with regard to preventing the COVID-19 illness or treating the symptoms. However, the recent excitement in the ability of umbilical cord stem cells in the treatment of COVID-19 was sparked by the treatment of a 65-year-old woman in Kunming Hospital intensive care unit, with apparently no hope of survival.

Researchers from Kunming University led by Dr Hu Min, gave the patient three doses of umbilical cord mesenchymal stem cells (MSCs) at different time points and, just four days after her first treatment, the woman was back on her feet. To date, eleven COVID-19 patients in China are reported to have been successfully treated with umbilical cord mesenchymal stem cells. Over the past two months, three new clinical studies have emerged to investigate the potential use of MSCs in the treatment of patients infected with the novel COVID-19 virus. These studies, in facilities based in China, are focused on using umbilical cord mesenchymal stem cells in the treatment of COVID-19.

The studies are part of a larger effort of more than 80 new clinical trials which are trying to tackle the fast- spreading virus. Why mesenchymal stem cells (MSCs)? MSCs are cells that can differentiate into a variety of cell types and are a most sought-after stem cells in the field of regenerative therapies and tissue engineering. In addition, Umbilical cord tissue contains, predominantly, MSCs, highlighting a reason why many parents are choosing to store them at birth.

Current scientific research has shown that MSCs have traits that can be used to treat infectious diseases, i.e. they exert immune regulatory functions, they have the unique ability to travel to damaged tissues, promote the regeneration and repair of damaged tissue, and reduce tissue damage. Currently, Health Agencies that authorise and inspect clinical trials of new medicines are reported to be on stand-by to ensure that applications relating to COVID-19 are dealt with rapidly, to enable a quick and longterm treatment for this pandemic. Therefore, the possibility exists that emerging clinical trials using umbilical cord mesenchymal stem cells may provide a breakthrough in the treatment of COVID-19.

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