Cord stem cells: donate or keep?

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Umbilical cord blood: what to do with it? Up until about thirty years ago, the delivery room routine involved ignoring it and throwing it away, along with the placenta and the cord itself. At a certain point, however, it was realized that it contains something precious: stamina cells useful for the treatment of diseases of the blood and immune system.

The first clinical use of cord blood is in 1988: little Matthew Farrow (5 years old), a native of North Carolina and suffering from Fanconi's anemia, receives a cord blood transplant donated by his little sister at the Saint-Louis hospital in Paris. , born without disease and immunologically compatible. The surgery was a success: Matthew recovered completely.

And so a few years later, in 1991, he was born in the United States first public bank for the collection and storage of donated cord blood, made available to anyone in the world who may need it. Then, they also arrived private banks (the first is from 1992) that allow you to store the stem cells of the cord exclusively, for a fee. In practice, it means keeping it for yourself - or, better, for your child or family.

So what to do with cord stem cells? Keep them or donate them? In this article we try to shed some clarity to help future parents to consciously choose what to do with their baby's cord blood.

In this article

• cord stem cells: what they are for
• autologous or donor stem cells
• keep stem cells for brothers or sisters
• the dedicated donation
• other uses of cord stem cells
• donate or keep: the opinion of scientific societies

The consolidated uses of cord stem cells

The collection and storage of umbilical cord blood at birth is becoming an increasingly common practice. The reason? The cells contained in the blood of the umbilical cord have a therapeutic value for the treatment of malignant and non-malignant blood diseases and immune diseases.

More precisely, umbilical cord blood contains all the typical elements of blood - therefore red blood cells, white blood cells, platelets and plasma - but it is also rich in hematopoietic stem cells, similar to those present in the bone marrow, which have a very important characteristic: they are pluripotent or "totipotent", that is, they can adapt to different purposes.

As Alice Bertaina, Associate Professor of Pediatrics at Stanford University explains: "these stem cells can be used to change the bone marrow of patients with diseases of the blood - such as leukemia, anemia, defects in the production of hemoglobin - or of the immune system, such as lymphomas, myelomas, immunodeficiencies. Or, again, congenital disorders of metabolism ". (The complete list of diseases treatable with hematopoietic cord blood stem cells is illustrated in a Decree of the Ministry of Health). cord stem cell transplantation replaces the classic bone marrow transplant, with several advantages. "For example - says Bertaina - it is easier to find a compatible donor and the risk for the recipient of developing a serious complication in which his tissues are attacked by the donor's cells is lower".

Among the disadvantages, however, there is the fact that the stem cells of a cord blood sample are not always sufficient for a transplant. "You need a certain amount per kg of weight: with children there are generally no problems, but with adults the cells are often too few." This is why we are trying to understand, especially in the United States, if it is possible to carry out transplants with several samples at the same time.

Read also: November 15, World Umbilical Cord Day

Do autologous donors?

In short, that the hematopoietic stem cells of the umbilical cord can be useful in some types of disease is beyond doubt. The crux of the matter, however, is to understand if - in case of need - they need to be autologhe, namely derived from your own cord blood put away in a private bank, or they may come from other donors, i.e. from a public bank. In the vast majority of haematological and immune diseases the answer is clear: stem cells not only can, but must come from a donor.

 

"Let's take the case of genetic diseases treatable with stem cell transplantation, such as thalassemia - says Letizia Lombardini, head of the tissues and cells area of ​​the National Transplant Center - it is clear that the patient's cells cannot be used, because they too contain the genetic defect that caused the disease. "An exception to this rule is if the stem cells, before being transplanted, undergo a procedure of gene therapy which allows you to modify their characteristics, making them capable of curing the disease without causing other damage.

This is precisely what we are trying to do with thalassemia, but beware: for all of this they don't necessarily need umbilical cord stem cells, even those that can be recovered from peripheral blood are fine.

Read also: Thalassemia: everything you need to know about the disease

Same goes for the cancers, such as leukemias, lymphomas and myelomas, and not just because the patient's stem cells could contain the predisposition to make the disease develop again. There is also another factor at stake, linked to the role of antitumor guardian of the immune system. "We know that the immune system can attack a tumor in its early stages of development, blocking its growth," Lombardini explains. "Evidently, if a person has fallen ill, their immune system has failed in this task and if after chemotherapy we give it back its stem cells, these will develop again into immune cells that are not very effective against any cancer cells left in the body. Stem cells from a donor, on the other hand, will be more useful also in this sense ".

What if we save them for a brother or sister?

In general, therefore, in cases where the hematopoietic stem cell transplant is consolidated, it makes no sense that cells from the sick person are used. But what if they were those of a brother or sister? And if, therefore, the cells of a newborn were placed in a private bank not so much for him, but for a close family member who already has, or could develop in the future, a curable disease with precisely those cells? In this case the advantage would be the immediate availability of almost certainly compatible cells.

Again, however, private storage may not necessarily be that useful, for different reasons. Let's see them one by one.

1. Because the probability that a brother or a sister needs, in general, the baby's cells is certainly not high.

It is not easy to make an estimate, but some authors have calculated that the probability that, in 70 years of life, a person may need the stem cells of a relative is between 0,25 and 0,5%. And you have to see if, after a few decades, those cells are still usable: at the moment we know that, if stored well, they can last up to 20 years, but we don't know what happens next.

The question of quality of conservation it is not a trivial matter: in many countries private banks do not have to comply with the rules laid down for public ones, and while many companies are serious, others are not at all. In the United States, an investigation carried out in 2022 by the Wall Street Journal brought to light serious defects and defaults on the part of some small private banks: sometimes the structures had even failed and nothing more was known about the cells that should have been preserved.

2. Because those in need of a hematopoietic stem cell transplant often find a compatible donor in a public bank

And obviously, the "richer" public banks are, the more likely individual patients are to find compatible cells: precisely the reason why in many countries - including the country - health authorities insist on the advisability of public donation or, as they say, solidarity.

The Del Paesena law, in fact, does not allow the autologous conservation of cord blood because it is inspired by criteria of solidarity and scientific evidence. The probability of using one's own cord cells is in fact very low (1 in a hundred thousand), while sharing in a public bank increases the possibility of finding compatible stem cells in the event of disease.

For more, in the public bank it is also possible to find any cells donated by a brother or sister: if they have not already been used by others - which is generally not very probable - they can easily be recovered by the family member.

3. Because even in the public sphere there are particular situations for which "dedicated" storage is allowed

The dedicated donation is specific for a single individual or a single family. "The cells placed in the bank cannot be used by others, but will be destined for use by the person who supplied them or by his family" explains Lombardini.

As indicated in the ministerial decree of 18 November 2009, the dedicated storage of cord blood in Del Paese is free.

Some numbers on cord blood donations in Del Paese in the last year

The Del Paesena network of Umbilical Cord Blood Banks (ITCBN) is made up of 18 banks and 270 collection centers located in all regions of the Paesene

 

Unfortunately, as emerges from the report of the National Blood Center, the Sars-CoV-2 pandemic has strongly penalized the collection of cord blood which has dropped by as much as 40% compared to 2022. According to the latest numbers available:

• total umbilical cord blood (CB) units were collected in 2022 5.742, equal to 2,1% of the births that took place in the collection centers. The previous year there were 10.661 for an incidence of 3,8% of the births that occurred;
• have been altogether 320 banked units, compared to 655 in 2022;
• as of 31 December 2022, 46.309 units of cord blood were available in the Del Paesene cord banks, of which 90,3% for non-family allogeneic use, 9,3% for dedicated allogeneic use and 0,4% for autologous.

The dedicated donation: that's when it's possible

The Ministry of Health has clearly defined when dedicated storage is allowed even within a public bank:

• cells of a newborn who has a disease - evident already at birth or discovery in the prenatal period - treatable with autologous hematopoietic stem cell transplantation, that is, of the infant himself. "There are rare cases of genetic diseases (for example ADA immunodeficiency) in which the stem cells are first treated with gene therapy, to avoid transplanting diseased cells" underlines Lombardini, recalling that these procedures are often still experimental.
• cells of a healthy infant who has a brother or sister already suffering from a treatable disease with the transplant.
• cells of a healthy newborn born from parents at risk of having other children with a treatable genetic disease in the future with stem cells.
• in the context of clinical trials for particular diseases.

The mesenchymal stem cells

In addition to the storage of hematopoietic stem cells, some private cord blood banks are beginning to promote that of another type of stem cell as well, called mesenchymal. They are cells capable of forming various tissues such as bone, cartilage and fat (and others), but also have anti-inflammatory and immune system modulating properties. They can be isolated from bone marrow, adipose tissue and, in fact, umbilical cord blood and cord tissue itself.

At the moment, some very promising trials are underway - and at an advanced stage. "They concern, for example, the treatment of some inflammatory diseases chronic diseases of the intestine, that of the complications that can follow the transplantation of hematopoietic stem cells and the regeneration of bone and cartilage "explains Alice Bertaina." And for the future the hope is to use them in various fields of regenerative medicine, for example for degenerative diseases of the eye, muscles, kidneys, brain ".

According to a systematic review of the literature, published last year, we still cannot claim victory over the use of mesenchymal stem cells. Although much research has already been done, in fact, still more studies will be needed to explore the therapeutic potential of these promising stem cells.

Furthermore, even in this case it is by no means certain that, in order to use them, it is necessary to recover these cells from the cord stored at birth. "If they prove to be really useful, they can also be taken from other sources, which are richer, or from the donor cord, because there is no need for a particular compatibility between donor and recipient" says Alice Bertaina.

Other uses of cord stem cells: where we are

As part of the treatment of diseases of the blood and immune system private storage doesn't seem particularly useful. However, if it continues to attract mothers and fathers there is a reason, and it is the prospect that, in the future, autologous cord stem cells can be used for other currently incurable diseases: brain trauma, neurodegenerative diseases, autism, inflammatory and autoimmune diseases.

In fact, this is a decidedly buzzing area of ​​research, with many studies and experiments carried out all over the world. In some cases, these studies seem to give encouraging results, but it should be remembered that a positive experimentation - perhaps conducted on a small or very small number of patients - is not enough to reach definitive conclusions. Is that many of these investigations, at the moment, rthey are still concerned with animal models of disease (i.e. they are studies on mice or other laboratory animals).

And again, if new treatments for these diseases will be available more or less soon, it is by no means certain that they will be treatments based on cord stem cells, moreover autologous, as the evolution of research in the case of infantile cerebral palsy is showing. and type 1 diabetes.

The case of infantile cerebral palsy

Over the past decade, numerous trials have been conducted for the treatment of infantile cerebral palsy through the use of stem cells.

Il first case of using stem cells of the cord blood in a child suffering from cerebral palsy is the one published in 2009 by Prof. A. Jensen, of the German University of Ruhr, Bochum

In this case, autologous stem cells from the same baby's umbilical cord were injected to repair the brain damage caused by cardiac arrest. In the subsequent clinical observation period, with the help of rehabilitation therapy, they were observed progressive improvements in the psychomotor development of the little patient.

Recently, a 20-month-old Del Paesena girl with infantile cerebral palsy also received two infusions of cord stem cells. Although it is too early for the doctors treating him to speak of real success, it would appear that the treatment has led to an improvement from the cognitive point of view and the ability to move, also recovering the ability to speak. The treatment was performed in the United States by Dr. Joanne Kurtzberg's team as part of a research, begun in 2008, which aims to analyze the effects of umbilical cord stem cells in neuronal regeneration.

At the moment, as ADISCO (Association of Donors Del Paesene Umbilical Cord Blood) also reminds us, despite some encouraging results, it will be necessary collect the results of other studies to confirm safety and therapeutic efficacy of this intervention.

Again, there is no evidence that autologous cord stem cells are "better" than those from a donor.

Read also: Infantile cerebral palsy: causes, consequences, therapies and quality of life

The case of type 1 diabetes

A decade ago, people began to think that cord stem cells could help out in the case of type 1 diabetes, a juvenile and autoimmune form of the disease. The idea was that they could exert an anti-inflammatory function able to mitigate the symptoms of the disease, for which the experiments with autologous cord stem cells have started. "The first results, however, were disappointing" declares Paolo Fiorina, one of the pioneers in the sector, who recently returned to Del Paese as head of the International Center of Reference on Type 1 Diabetes at the Sacco Hospital in our city, after 12 years at Harvard Medical School in Boston. "There was some improvement in the inflammation indices, but there was no effect on blood glucose and the disease remained as it is."

Recently, the turning point. "Some studies have shown excellent results with stem cells purified from peripheral blood, and reinfused into the patient together with a cocktail of anti-inflammatory substances "remembers Fiorina. According to whom the future - in the case of type 1 diabetes and other autoimmune diseases - it would not belong to the cord stem cells, but to other types of stem cells, such as those that can be recovered from other tissues (bone marrow, peripheral blood, adipose tissue) or even created in the laboratory from already differentiated cells.

Donate or keep? The positions of the scientific community

So what to do with this cord blood? Many women ask themselves this, undecided between private conservation and public donation. The choice obviously remains individual, but for various health authorities the answer is clear: better to focus on public banks. In the United States, for example, the Association of Obstetricians and Gynecologists, the Association of Pediatricians and the Society for Bone Marrow Transplantation have declared their opposition to private conservation.

In Del Paese, private storage is not allowed, but those who want can get around the obstacle by turning to foreign companies, which operate in a very widespread way in our territory. The official position on the subject is that expressed in a document prepared by the National Transplant Center and the National Blood Center in collaboration with various scientific societies (Position paper of 10 January 2022). The document explicitly discourages storage for personal use "intended as biological insurance for the infant or the family", because it believes that does not comply with "principles of effectiveness and appropriateness".

Other experts have a more possiblist position. A document from the Canadian Society of Obstetrics and Gynecology states that in the future, with the advancement of medical technologies available, starting with gene therapy, the likelihood of using cord stem cells, even autologous, could increase, but which at the moment is " impossible to predict the future value of autologous conservation ". And therefore recommends that families should be provided very clear and transparent information on current possibilities and future prospects for use.

And in an article published in 2022, some of America's foremost stem cell transplant experts conclude that while they themselves continue to recommend public donation, private storage may also make sense in the future in the area of ​​regenerative medicine, in particular for the treatment of neurodegenerative diseases. And they underline that in the future there could be opportunities for collaboration between public and private banks: "mixed" situations in which "private" cordons could be donated to public banks if not used by the family that locked them up. "Provided - underline the authors - that private banks really operate with qualitative standards comparable to public ones and that the techniques on which we are working today prove to be really effective". Which at the moment is not taken for granted.

Other sources for this article:

• C. Petrini, Umbilical cord blood banking: from personal donation to internazional public regitries to global bioeconomy, in "Journal of Blood Medicine", 2022;
• Interview with Matt Farrow, Recipient of World's 1st Cord Blood Transplant, in Parent's Guide to Cord Blood/Foundation;
• advice from Dr. Alice Bertaina, Associate Professor of Pediatrics at Stanford University;
• advice of National transplant center;
• advice of Letizia Lombardini, head of the tissues and cells area of ​​the National Transplant Center;
• advice of Paolo Fiorina, director of the International Reference Center on Type 1 Diabetes at the Sacco Hospital in our city;
• articolo Umbilical cord blood donation: public or private? (Bone Marrow Transplants, 2022);
• articolo Regenerative Therapy and Immune Modulation Using Umbilical Cord Blood–Derived Cells (Biology of Bone and Marrow Transplantation, 2022);
• National Transplant Center Focus on Infantile Cerebral Palsy;
• Umbilical cord blood banking, ACOG Scientific Opinion (December 2022);
• Position paper of the National Transplant Center (and others) on cord blood collection and storage (January 2022);
• Umbilical Cord Blood: conuselling, collection, and banking (September 2022), by the Canadian Society of Gynecology and Obstetrics;

- Updated on 29.10.2022

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• umbilical cord
• cord stem cells
• cord conservation
• cord donation
• cordon banks
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