Author: Dr. Lana du Plessis

stem-cell-success-story-pippie-kruger

Pippie Kruger: a courageous stem cell success story

Isabella “Pippie” Kruger was made famous when, as a 2 and a half-year-old burn victim from Limpopo, she received a ­revolutionary skin transplant operation. Pippie was severely burned when a bottle of gel firelighter exploded while her father was lighting a braai on New Year’s Eve. She suffered 80% full thickness third-degree burns. She was given a 3% chance of survival by her doctors. The skin graft was grown from her own cells in a laboratory in the United States, because the technology was not available in South Africa. It was the first time the procedure was performed in Africa.  However, 5 heart attacks, 5 strokes, kidney failure, lung collapses, sepsis and almost 60 operations later, she survived.

The medical director, Dr Barrett at Genzyme-Sanofi, a pharmaceutical company owns the rights to the technology known as Epicel. Epicel produces skin for people with extensive burn wounds by extracting stem cells from small patches of patients’ healthy skin. They are placed on a layer of inactive mice cells and fed with special proteins that allow them to grow into thin layers of skin that can cover burns. Epicel is indicated for adult and pediatric patients who have deep dermal or full-thickness burns comprising a total body surface area greater than or equal to 30%.

The skin was cultured in America and sent to Johannesburg on a 21-hour flight and working with plastic surgeon Ridwan Mia to ensure that it was transplanted to Pippie within three hours of arriving in South Africa.

The Epicel procedure is a costly procedure and luckily the Kruger family managed to raise more than R700 000 for the Epicel procedure through a trust fund that was started by a friend. With the help of  Facebook and almost 10 000 followers, this was accomplished. Pippie’s story has been told in 71 newspapers across the world and by many global radio and television stations.

Pippie now 13 is no stranger to the operating table. Since the disastrous burns accident she suffered as toddler, the young girl has been through a gamut of surgeries, and recently she had her 62nd operation.

Her mom, Anicè, for whom hospitals and air travel have become a way of life, believes this procedure has made a significant difference to her daughter’s quality of life.

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.

Epigenetics and Motherhood

What does Epigenetics mean?

Gene expression is the process of how often or when proteins are produced from the blueprint within your genes. While genetic changes can alter which protein is made, epigenetic changes affect gene expression to turn genes “on” and “off.” Since your environment and behaviour, such as diet and exercise, can result in epigenetic changes, it is easy to see the relationship between your genes and your behaviour and environment.

The study of epigenetics looks at how actions and the environment can influence your genes. Unlike genetic changes, epigenetic changes are reversible and do not change DNA sequences, but they may affect how your body reads DNA sequences.

How does epigenetics relate to Nature Vs Nurture?

Epigenetics explains how early experiences can have permanent effects. The genes children inherit from their biological parents provide information that guides their development. For example, how tall they could eventually become or the kind of temperament they could have.

How does epigenetics affect us before birth?

Environmental factors may alter the epigenetic profile of a fetus during early life, specifically in the prenatal period, which may increase vulnerability to diseases later in life, such as obesity, cardiovascular, diabetes, etc.

Donor Eggs Epigenetics and Birth Mother.

Birth mothers using donor eggs have a significant impact on the development and future health of their babies. Since the baby’s DNA only comes from the egg donor and the sperm donor, many women using egg donation worry that they will not share any genetic information with their child.

However, the switches that turn our genes on and off may play an even greater role in health and development. These switches are known as epigenetic controls. Abundant research has shown us that the prenatal uterine environment plays a crucial role in fetal brain development, childhood metabolism, immune health, and numerous other factors.

Given our limited understanding of the processes that affect fetal development, what can a pregnant woman do to improve her prenatal environment? Following the common practice most women use during pregnancy might be the best approach in order to foster a healthy uterine environment for your baby, it is essential that you maintain a good weight, follow healthy diet habits, refrain from drinking alcohol, limit caffeine intake, and take prenatal vitamins. Stress management and maintaining stress-reducing activities during pregnancy are equally important for creating a healthy uterus for your baby.

An emerging concept, fetal adaptation, explains how epigenetic regulation impacts development later on in development, in contrast to embryogenesis and implantation early on in development. Epigenetic modifications allow the fetal genotype to respond to a variety of developmental environmental factors. Even though early gestation is the most susceptible period for the fetus, environmental stimulation in late embryonic development, infancy, and early childhood can also have long-term health effects in later life. It has been shown that a high-fat diet supplemented in adulthood induced large-scale methylation changes in skeletal muscles, as did folic acid supplementation during the peri-pubertal period. All these studies suggest that plasticity of the human epigenome may also persist into adulthood and epigenetic mechanisms are involved in life-long adaptation.

In conclusion:

In contrast to conception, which begins when an egg cell meets a sperm cell, motherhood begins in the womb. The factors influencing childhood begin in the mother’s body long before she becomes pregnant. Your uterine environment will influence your baby’s development in various ways. When you begin taking care of yourself before you become pregnant, and continue doing so as your baby develops inside you, you’ll be able to pass on health benefits to your child, ensuring they have the best possible future.

Delayed Cord Clamping

The subject of delayed cord clamping (DCC) has been researched and discussed in numerous studies. The most important consideration at the time of the delivery is the health of the mother and baby. Delayed cord clamping has been shown to be beneficial to the baby and thus in the setting of cord blood banking, delayed clamping is an acceptable practice and is encouraged.

Recent studies have shown that DCC show an increased amount of red blood cell stores in newborns and thus lessening the risk of iron deficiency anaemia later in the baby’s life. This is specifically important in preterm babies and those at risk of anaemia. In very preterm babies (22 weeks–28 weeks), DCC for 30 seconds, or more, has led to increased survival and a lowered risk for severe neurological injury. In further studies, DCC also showed an improvement in fine-motor and social skills in kids at four years of age in comparison to kids of the same age that had no cord clamping at birth.

There is, however, a small risk of increased hyperbilirubinemia/jaundice (because of the additional red blood cells infused during DCC) in some infants after DCC. An estimated 50% of term and 80% of preterm infants develop jaundice.

Delaying cord clamping for one minute or more resulted in only a 6%–21% decrease in the total volume of cord blood collected and a 9%–31% decrease in the pre-processed total nucleated cell. It is estimated that about 60% of DCC collections still meets the upper level for the number of total nucleated cells. However, a prolonged delay will allow the blood in the cord to clot, and the opportunity to collect the blood for stem cells will be lost; therefore, if clamping is delayed, it is recommended not to delay for more than two minutes.

What major myths exist relating to the optimal clamping time?

Myth: If you don’t do DCC, you are robbing the baby of 30% of its blood.

Fact: When the umbilical cord is clamped soon after birth, the infant’s blood volume is the same as its volume in utero (in the womb).

Myth: The longer you wait to clamp the cord, the more blood the baby gets.

Fact: The continued transfusion of cord blood when delaying the clamping in normal birth is reliant on contractions of the uterus, the umbilical arteries close around 45 seconds after birth and the umbilical vein in 1–2 minutes. For c-sections, the blood volume in infants increases till 40 seconds and actually decreases thereafter.

Myth: Delaying the clamping of the cord confirms the advantages observed by researchers.

Fact: Factors affecting the transfusion of additional blood cells include the timing of cord clamping, gravity, the onset of respiration, uterine contractions and drugs affecting it, maternal blood pressure and birth asphyxia.

Facts relating to COVID-19 and delayed cord clamping

The use of delayed cord claping during COVID-19: Most Gynaecological institutions have stated that these procedures should remain according to usual centre practice, while following infection control precautions. They have stated that delayed umbilical cord clamping is extremely improbable to increase the risk of transmitting pathogens from an infected mother to the fetus; however, some institutions have selected to forbid this exercise in term infants, in whom the benefits are modest. This practice they believe will minimise newborn exposure to any virus in the immediate environment and reduce the chances that the newborn will require phototherapy for jaundice. Some institutes also prohibit skin-to-skin contact in these cases, although the Paediatric institutions have not advised against this.

References

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.

Newsletter November 2021

Good day to all our valued clients.

As the year draws to an end, I thought I would take the time to reflect on the last 18 months.

It has been a tough year for all businesses and everyone in general, as the Covid-19 pandemic has strangled our economy. We have seen financial, family and personal pressure being placed on individuals as well as businesses due to this pandemic. Let’s hope that the comprehensive rollout of the vaccine in the country will aid us all in surviving this pandemic and hopefully in the near future the world can revert to some form of normal.

At CryoSave we have remained busy and have worked within the parameters of the lockdowns and regulations and we see light at the end of the tunnel. Our access to hospitals and medical professionals has increased since 18 months ago. This is encouraging and gives us some comfort that we are heading in the correct direction.

There is a lot of interesting research going on in the field of regenerative research which hopefully could result in many more treatments being approved by the relative authorities for various conditions. The limits as to what treatments will be offered using stem cells have yet to be determined and it will be very interesting to follow the new breakthrough treatments that are on the way. We will keep you informed as we learn more.

As the festive season approaches, I would like to take this opportunity to wish you all a very safe and healthy festive season. Hopefully, you all get to spend quality time with your loved ones and also have a decent well-deserved rest. I believe the pandemic has taught everybody the value of having quality time with our loved ones, as many of us were separated for long periods of time over the last 18 months.

Kind regards,
Donald Gilroy
Chief Executive Officer


This month’s articles

What is regenerative medicine/therapy?

This month’s article will centre around Regenerative Therapy and its potential healing benefits. The main benefits of this therapy are the healing or replacement of tissues or organs that have been damaged by disease and trauma.
The field of regenerative therapy is still relatively new and if you would like to know more about the groundbreaking research and healing properties, this article will answer all the questions that you may have.

Learn More

Delayed Cord Clamping

Delayed cord clamping in its definition, implies that doctors don’t immediately clamp and cut the umbilical cord. Instead, they allow extra time for the blood in the cord and placenta to flow to the baby. According to various studies and research, Delayed Cord Clamping has been shown to be beneficial to the baby and thus in the setting of cord blood banking, delayed clamping is an acceptable practice and is encouraged. For more on this, we have written an article for your perusal.

Learn More


Seasons wishes from our Medical Director

The past year has been an extremely exciting one in the field of stem cell research and advances in the field have been significant. The potential use of stem cells in medicine is increasing rapidly and there is little doubt in my mind that stem cells are going to play a very significant role in medicine in future. One of the most significant advances has been the ability to expand (multiply) the cells. Up to now, a single sample only contained enough stem cells for one treatment. With expansion technology we now have the potential for multiple treatments from a single sample. Research in the expansion field is ongoing and I believe that we are not too far from the practical application of this technology. We are all looking forward to a very promising and productive 2022.

I would like to take this opportunity to wish all at CryoSave as well as our extended CryoSave family and our future family a happy and peaceful holiday season and an exciting and productive 2022.

I would like to take this opportunity to wish all at CryoSave as well as our extended CryoSave family and our future family a happy and peaceful holiday season and an exciting and productive 2022.

Seasons wishes
Dr. Peter Koll
Medical Director


Read our customer stories

Bailey Schneider & Tracey McGregor share their stories of motherhood and the reason they chose to store their children’s stem cells with us.

Read our reviews

A summary of the pros and cons of cord blood banking

Stem cells are unspecialised cells present firstly in the embryo during prenatal development and later in adult life. These cells can replace damaged cells and develop into any specific cell of various tissue types when required by the living body. In adults; stem cells are found in various tissues such as blood, bones, brain, skin, and liver. However, during the developmental stage of the fetus, the umbilical cord serves as an essential source of nourishment to the growing fetus. The blood of the cord and the tissue of the cord is another highly enriched source of stem cells and these important cells can be cryopreserved at birth to assist in treating numerous diseases and conditions.

Cord blood banking Pros

1. Painless Process

The process of collecting blood from a newborn is entirely non-practical and painless for the mother as well as the baby.

2. Devoid of Health Risks

The banking of cord blood is a risk-free procedure for the baby and the mother.

3. Increased Effectiveness

Cord blood stem cells have an increased advantage of easier tolerability, reduced rejection and mismatching concerns than bone marrow stem cells.

4. Decreased Chances of Graft Diseases

The chances of graft diseases after transplantation are higher with peripheral blood and bone marrow stem cells as compared to cord blood.

5. Prolong Storage

Apart from the easy collection of cord blood, it can be stored for 20 years or more (given it is stored under the industry approved controlled conditions). When cryopreserved, cord blood has a longer shelf life for usage after many years of collection. Bone marrow blood cannot be preserved for a longer duration.

6. Immune System Reinforcement

Cord blood has the added advantage of being used to boost immunity of patients, during the treatment of cancer. Researchers are using cord blood stem cells to increase the immune system of cancer patients after chemotherapeutic treatment of cancer. This treatment provides for better outcomes and recovery of cancer patients.

7. Increased Proliferation Capability

The stem cells from cord blood have increasing dividing capacity and therefore when transplanted in a recipient will give better results than bone marrow or peripheral blood. The yield of cord stem cells is about 14 times greater than cells from other sources when comparing the volumes collected.

8. Less likely to have infectious agents

Stem cells from cord blood rarely carry any infectious diseases and are half as likely to be rejected as adult stem cells.

9. Future Insurance for Child

The banking of cord blood offers reliable and useful choices to parents for saving their child’s health prospects. This process is like health insurance for your children and direct family, due to the similarity in genetics the probability of being a match for siblings is 25% and 50% for parents. Thus the saving could provide a cost saving in the long run when comparing a transplant from a non-related adult stem cell source.

10. Assisting Humanity

Due to improved chances of donor receipt of stem cells into the foreign body, the cord donor blood could prove to be an extraordinary relief to many sufferers. The donation of cord blood is motivated by the certain health agencies as it can serve as an outstanding transplantation opportunity in many recipients.

11. Helping Family Members

In case of medical problems, providing stem cells from a child could be a source of medical assistance to siblings, parents or any other family member, due to inheritance similarities.

Cord Blood Banking Cons

Although there are disadvantages, there are ways to overcome these challenges and we mention these below.

1. Ineffective Treatment in Adults

Because of the limited volume of cord blood available from the source, most adults cannot be treated with the number of stem cells collected at birth. Therefore the expansion of cord blood and tissue stem cells have now provided an increased usage of cord stem cells in general.

2. Autologous Transplantation

Refers to the treatment of the same child with his/her own stem cells. The only drawback is when a child has a genetic diseases or blood cancer because the stem cells will then carry the same genetic makeup and cannot be used. In this case it is recommended to store sibling cord stem cells in the event that the sibling stem cells can be used.

3. Immediate Collection

Though, the cord blood banking is related with the easier collection but immediate collection at the time of birth of a baby is necessary. It is recommended that parents make informed decisions and plan long before birth. Therefore CryoSave offers Emergency Kits at most hospitals to assist with this “on the spur of the moment” decision in some families.

4. Slow Engraftment

The cord blood stem cells show slow grafting due to the fact that the white blood cells appear later in grafting from cord blood as compared to stem cells from bone marrow transplantation. This can be improved by double unit transplants or by also expansion of cord stem cell grafts ex vivo (outside the body) to increase the cell dose.

5. Ethical Concerns

The use of cord blood and tissue has restraints due to ethical issues, but these are overcome by clinical trials that are demonstrating the value of these precious stem cells in the treatment of many diseases; i.e. autism, cerebral palsy, multiple sclerosis, diabetes, cardiovascular disease and many more.

Reference:
  • Cord Blood Banking – American Pregnancy Association. November 04, 2018.

COVID-19 in pregnancy

This opinion article was written by Dr. Peter Koll, CryoSave Medical Director and a renowned specialist Obstetrician and Gynaecologist who has been in private practice for over 27 years.

“I believe that it is important to point out from the onset that there is a lot that we still do not understand about COVID-19. What we do believe and the advice that we give may change before and after the publication of this article, which is 01 September 2021.

Initially, we thought that pregnant women are equally likely to get severe disease than the non-pregnant population. However, studies have indicated that there are some increased risks in pregnancy. It is important to understand that although certain risks are increased in pregnancy, the overall risk of severe disease is still low and the vast majority of pregnant women who contract COVID will have mild disease. Two-thirds of women who get COVID in pregnancy will have no symptoms at all, the majority of those who develop symptoms will experience mild flu-like symptoms, and only a very small number will develop severe disease. In addition, women who fall pregnant tend to be younger and healthier than the general population.

Some factors increase the risk of developing severe disease in pregnancy. These include pre-existing diabetes, high blood pressure, obesity, and being over the age of 35. People of Black, Asian and Hispanic origin have also shown an increased risk to severe disease.

Pregnant women who develop severe disease will have a greater chance of needing admission to ICU and a greater need for mechanical ventilation. There is an increased risk of developing blood clots as well as an increased risk of premature birth and fetal loss, nevertheless, the absolute number of these complications remains small. Needless to say, the vast majority of women who get infected with COVID will have mild disease.

Mother-to-baby transmission is uncommon and most infected babies have mild symptoms or no symptoms at all. The method of delivery does not seem to affect the infection rate in the baby. It is thus most likely that if the mother has COVID in her pregnancy, the baby will not be infected.

Vaccination is advised in all women contemplating pregnancy, as there is no current evidence linking the vaccine to infertility. If you are pregnant, vaccination is strongly recommended. There is no evidence that the vaccine could harm your baby but as a precaution in South Africa, it is suggested that you vaccinate after 12 weeks. If you get the vaccine in early pregnancy, before you know you are pregnant, there is no evidence to suggest that the baby will be harmed. The choice lies with you as parents, whether you vaccinate before you know you are pregnant, after the first trimester, or even soon after birth, there is no indication that it could harm your baby.

There is however a small increased risk of severe disease in pregnancy, especially if the known high-risk co-morbidities like diabetes, obesity, and high blood pressure are present as well. Be extra careful about wearing a mask, social distancing, washing hands, and disinfecting, as well as avoiding crowds and gatherings.

The South African Society of Obstetricians and Gynaecologists (SASOG) has a website with very useful and regularly updated information on COVID in pregnancy. Search for SASOG, and the section on COVID in pregnancy will be easy to find.

The Royal College of Obstetricians and Gynaecologists (RCOG) also has a patient information section on their website covering a large number of topics. The section on COVID also contains links to other useful sites. Search RCOG and look for “COVID in pregnancy”.”

Further reading:

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.

Graft-versus-Host Disease: Know your donor

For more than five decades, Haematopoietic (blood-forming) stem cell transplantation has been recognised as potentially curative therapy for certain types of cancer and non-malignant disorders.

Umbilical cord blood has emerged as a viable alternative source of blood-forming stem cells which could be made available, without delay, to the child or a sibling. Parents now have the ability to store (‘cryopreserve’) their newborn baby’s cord blood stem cells in a family cord blood bank.

Once done, a cord blood transplant (CBT) becomes an option for the Transplant Team and may obviate the need to search for a matched, unrelated donor.

One of the main benefits of cord blood, as a source of stem cells, include the simplicity of collection at the birth of the baby, with no risk to mother or baby. There are two ways of collecting the stem cells:

  • The ability to immediately bank these samples in a family (private) stem cell bank, for future use by the child (donor) or a sibling.
  • Cord blood stored in ‘public’ cord blood banks are made available for use by non-related individuals. These cord blood stem cells can be made available for transplant, without delay, and are more ‘naïve’ than the other sources of blood-forming stem cells i.e., bone marrow (BM) and peripheral blood stem cells (PBSCs).

Defining Graft-versus-Host Disease

The day-to-day task of a person’s immune system is to protect it from foreign invaders, be it a bacteria, virus or other organisms or cells that are not identified as ‘self’.

When a person needs a stem cell transplant, a donor, who is a match for the specific patient, must be found. This is what we call Human Leukocyte Antigen (HLA) matching or, in non-medical terms, “flags” that the immune system must look at to determine if something is an invader. With a stem cell transplant, the recipient will receive donor stem cells and these cells will form new blood as well as an immune system in the recipient.

Higher levels of differences of human leukocyte antigen (HLA) matching can be tolerated with CBT, confers a potential advantage. Also, some studies have shown a lower incidence of graft-versus-host disease (GvHD) with CBTs compared to bone marrow and peripheral blood stem cell transplants.

These features make a cord blood transplant as a potentially important option in patients from diverse, cultural and ethnic backgrounds as, for these patients, it can often be challenging to locate a matched unrelated donor (MUD).

With a stem cell transplant, even after HLA matching, the patient/recipient’s body will still see small differences between the new developing immune system and other cells in their body. Therefore, the recipient’s “new” immune system may harm some of the recipient’s cells because they are seen as “different”. This immune attack (on the recipient) is called Graft versus Host Disease (GvHD). The word ‘graft’ referring to the donor’s cells, and the ‘host’, to the patient (recipient).

The good of Graft-vs-Host-Disease

GvHD can have a ‘good’ aspect as it indicates that the recipient’s new immune system is working and is likely to be attacking any remaining or returning disease. This type of immune response is called ‘graft versus leukaemia effect’ or ‘graft versus tumour effect’. However, extreme GvHD can cause undesirable problems and side effects which is life threatening.

The not-so good

GvHD is complex and cannot be predicted. Approximately, 30-40% % of transplant recipients will show signs of GvHD. In certain cases, it is mild but, in severe cases, may be life-threatening.

GvHD can be classified as the following:

  • Acute: occurring within the first 100 days after transplant
  • Chronic: usually occurring after 100 days and
  • Overlap: having features of both acute and chronic GvHD.

GvHD affects organs such as the skin, liver, and gastrointestinal system.

It usually requires a fine balance of medication to keep the disease under control. Treatment includes localised and/or systemic steroids or immunosuppressive medication. In some cases, acute or chronic GvHD cannot be controlled with these medications and further treatment, such as extracorporeal photopheresis (ECP) (where the white blood cells that cause GvHD are destroyed with medication and ultra-violet (UV) light, is required).

Several strategies exist to further improve outcomes in CBT and minimise GvHD even further:

  1. The use of double CBT from unrelated donors
  2. The use of HLA-identical sibling CBT
  3. The use of a combination of UCB and bone marrow from the same sibling,
  4. The use of higher cell doses in conjunction with microenvironmental factors and, for example, the combined use of mesenchymal stem cells.

These strategies are designed to enhance the ‘homing’ and engraftment of the transplanted cells and improve success rates overall.

Final words

Parents should consider storing their baby’s stem cells at birth, which would give the Transplant Team an option should a stem cell transplant be needed.

Did you know

Since the first cord blood transplant in 1988, more than 40,000 CBTs have been performed, worldwide, over the past three decades.

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