Cord Blood: Hope for Coming Generations

In truth, this isn't an easy decision. First of all, storing cord blood costs a whopping NT$70-80,000, not something every household can afford; secondly, what exactly is it that's being stored, and what are the odds that it would be needed? Alas, nobody really knows.

What exactly are we saving when we store cord blood? What exactly do the stem cells in the blood do? Is private storage better? Or public donation? Should parents who don't store their children's cord blood feel ashamed or ill at ease?

Last February, Dr. Lin Kai-hsin, attending physician of National Taiwan University Hospital's Pediatrics Department, attempted a transplant of "autologous" cord blood (i.e., cord blood from the patient's own body) on a young boy surnamed Wang who had cerebral palsy caused by hypoxia (lack of oxygen in the brain).

To avoid risks involved with direct injection into the brain or cerebrospinal fluid, Lin used the safest method: injecting cord-blood stem cells into young Wang's veins.

"It's his own cord blood, so it won't be rejected. It's safer than transplanting other people's cord blood," says Lin. Even though the existence of hematopoietic (blood-building) stem cells in cord blood has been confirmed and they are widely used in the treatment of blood diseases, medical experts are still debating the utility of the mesenchymal stem cells (i.e., those able to grow into mid-layer tissues) found in cord blood, such as whether brain cells damaged by hypoxia can be repaired through cord blood transplantation. At present this remains unsettled at the clinical level.

Lin says that the US Congress has reported on two cases in which patients have displayed steady progress, and 16-month-old Wang has improved to the point where he can stand up and walk after six months of continual post-transplant observation by pediatric neurologists. But how much of this can be credited to the stem cells? How effective are they in rehabilitation? Can young Wang's damaged brain cells start to heal as a result? It's too early to tell, and five or six more years of observation are needed.

At any rate, this was the first-ever autologous cord blood transplant in Taiwan; indeed, it's the sole instance of autologous cord blood use out of a total of 40,000 people in Taiwan who have stored cord blood.

8. Storage in liquid nitrogen at -196oC

Catching up

Though autologous cord blood transplants are rare, there have been nearly 10,000 allogeneic transplants (i.e., using blood from other people) since the first successful case in France in 1988. In Taiwan, the first case was handled by Lin.

In 1990, Lin went to the US to learn how to collect and use cord blood. After returning to Taiwan, starting in 1995 he gathered cord blood from relatives, mainly siblings, to treat more than 30 serious cases of childhood leukemia and neuroblastoma. But there were only five instances among them in which the white blood cell antigens were a match, meeting the criteria for cord blood transplant.

Sadly, these five were all serious cases, compounded by the poor post-surgery care skills of the healthcare teams of the time, which would frequently lead to infection. In some cases there was post-transplant relapse, and in the end none survived.

As for the first case of cord blood transplant between relatives in Taiwan, in 1995 Lin injected a nine-year-old leukemia patient with his sister's cord blood. After the transplant, the boy's hematopoietic immune cells successfully transformed into those of his sister's (the chromosomes also changed from XY to XX); however, there was still a slight rejection, so anti-rejection drugs needed to be administered. Unfortunately, these drugs also lowered the patient's immunity. Even though the medical team struggled to maintain balance, the boy tragically died as a result of infection.

As for the first case in Taiwan of cord blood transplant from a non-relative, it's none other than Lin Po-chih, the well-known mucopolysaccharidosis baby, the ups and downs of whose progress we followed intently with joy and sorrow.

Mucopolysaccharidosis is a genetic disease, and all three boys in the Lin family had inherited it. A transplant from a relative was out of the question, and the only option was to seek a match from among all the private and public bone marrow and cord blood banks. In 2000, Dr. Lin managed to find a bag of blood from the Cord Blood Banking Program (founded in 1999) of the Taiwan Blood Services Foundation (TBSF), which was a match for baby Lin. But after the transplant, the stem cells did not proliferate as expected. After six months, another matching bag was found at Sun Yat-Sen Cancer Center's cord blood bank. The stem cells grew after the transplant, but symptoms of rejection occurred, such as serious skin inflammation, and anti-rejection drugs were needed to suppress it. In the end, baby Lin lost the battle amid the predicament of countering rejection versus maintaining immunity, and, like so many other cord blood transplant patients, died of infection.

Despite freeing sufferers of Cooley's anemia from the life-long anguish of blood transfusions and shots of iron chelator, bone marrow and cord blood transplants bear their own risk: that of tissue rejection. Careful assessment is needed.

What do stem cells do?

Stem cells are primal cells, with the functions of hyperplasia and differentiation. Hyperplasia denotes the ability of a cell to subdivide over and over again into tens of millions of cells, while the capacity to change into cells with different physiological functions is called differentiation.

Chang Nan-chi, founder of the Taiwan Society for Stem Cell Research and a professor at the Graduate Institute of Microbiology and Immunology of National Yang-Ming University, states that stem cells can be divided into four "generations" according to the degree of differentiation. Before dividing into four to eight cells after fertilization, stem cells are "totipotent": at this time, a single cell can grow into an entire organism. After further division, the second-stage stem cells become "pluripotent"-able to differentiate into the cells of any tissue or organ (cord-blood stem cells belong to this category). The third stage is that of "multipotent" cells, including bone marrow and peripheral blood stem cells, which have immune and hematopoietic functions. The fourth stage consists of "unipotent" stem cells: for example, those of red blood cells can only grow into red blood cells; those of neurons can only become neurons.

Life is like a competitive game of tug-of-war: we must do our utmost, never slacking, until the end.

Where are stem cells found?

Throughout the life of a human being, stem cells can in fact be found in all organs, bearing the job of regenerating and repairing tissue and organ cells. It's just that they are few in number and can't be found with present-day technology, so we must extract blood from the umbilical cord at birth for storage for future use. If we miss this opportunity, our only choice is to find traces of stem cells from bone marrow and peripheral blood. Thus, the marrow and peripheral blood of adults (minors under 18 cannot donate blood or marrow) and the cord blood of newborns are our principal sources of stem cells at this point.

Each of the three stem cell sources has its advantages and disadvantages (see table). Checking the figures, we find that the highest concentration of stem cells is in cord blood, with marrow coming in second, and peripheral blood the lowest.

Bone marrow donation is a surgical procedure, with issues like anesthesia risk and post-operative pain; indeed, some people experience prolonged bone pain after the procedure. Although donating peripheral blood doesn't require surgery, there are still potential risks-trials on rats have shown that after injection with leukocyte hyperplasia drugs, the occurrence of leukemia increases. Though this result hasn't yet been verified in humans, donors need to be aware of the risk. On the other hand, the umbilical cord is not part of the human body, so cord blood donation causes no pain and the risk is low. The only danger is that if it's all donated to others, you will need luck to find a match if one day you need it for yourself.

Looking at the functions of stem cells, bone marrow and peripheral blood contain later-stage cells, with only immune and hematopoietic functions. The stem cells in cord blood, however, are primal cells that have not completed differentiation, and thus have the potential to develop into any cell type, offering wide applications in treatment, such as repairing brain damage in patients like young Wang. Moreover, there are lymphocytes in adult peripheral blood and bone marrow, so the chance of rejection is greater; there may even be some cancerous cells. But because the stem cells in cord blood are "young," there are no immune lymphocytes, and there are no cancer cells mixed in with them.

Current stem cell research is divided into two areas. The first concerns hematopoietic stem cells, which can develop into blood and immune system tissue; the second concerns mesenchymal stem cells, which can differentiate into neurons, liver cells, myocardial cells, fat cells, cartilage cells and so forth. The former have been verified in clinical trials and are widely used in treating aplastic anemia, Cooley's anemia, leukemia and other diseases of the blood. The latter, however, is still in the experimental stage, as yet clinically unverified.

All-powerful stem cells?

Though the cord blood transplant procedure is simple and low cost, the amount of cord blood totals just around 100 cubic centimeters, so that it only contains a limited number of stem cells; thus there are still limitations and risks.

"The quantity of stem cell matching is the key to the success or failure of a cord blood transplant," says Lin. Most cord blood transplants can only be conducted on children who weigh no more than 30 kilograms, the reason being the limited quantity of stem cells in the cord blood.

In the case of childhood leukemia treatment, prior to a transplant the patient first needs to undergo chemotherapy or electrotherapy to kill the cancer cells in the body. Then the stem cells are injected. Until the stem cells grow and perform their function, the patient is completely without hematopoietic function, so in addition to the problem of anemia, cord blood also lacks white blood cells and platelets. Infection and bleeding can easily occur during this window of danger, and any mistake can jeopardize the patient's life.

Closeness of match is the most basic requisite for a cord blood transplant.

The genes for human leukocyte antigen (HLA) are on six different sites on one chromosome; these include HLA-A (of which there are 396 genotypes), HLA-B (669 genotypes) and HLA-DR (494 genotypes). At least five need to match if rejection is to be avoided. But in reality, there are many secondary genes involved besides these six sites on the DNA strand. Since there are fewer genotypes among them, we don't have to be as concerned about these genes, but at present no one dares make the final word on whether these will affect the results of treatment or produce other unforeseeable effects.

"There's only one person in the world who will completely match you, and that's you!" says Chang. Plastering ads around saying things like "Store one person's blood and the whole family benefits" or "Save Grandma, have a child" are wrong to begin with; even with a sibling, the chance of a genetic mismatch would still be very high, and this is the major reason he wishes to promote the storage of autologous cord blood.

"In particular, the HLA of Aborigines is quite different from that of other people in Taiwan. If they don't store their own cord blood, it will be hard to find a successful match from a cord blood bank," says Chang.

8. Storage in liquid nitrogen at -196oC

Private storage vs. public donation

Given the enormous promise of stem cells and the fact that only one's own stem cells guarantee a quick match without rejection, should cord blood be privately stored or donated publicly? This is a dilemma long faced by the medical community.

In Taiwan, cord blood storage institutions are divided into two types: public banks that take donations, and private banks.

The public banks take donations free of charge. Taiwan's public cord blood banks include the TBSF's Cord Blood Banking Program, the Tzu Chi Bone Marrow and Stem Cell Center's cord blood bank, the Sun Yat-Sen Cancer Center's cord blood bank, and StemCyte.

Private banks are paid for by the contributor, and use is limited to the cord blood's owner or the owner's relatives. Currently there are some nine private cord blood banks in Taiwan; one of them is BabyBanks, belonging to the eight-year-old Bionet Corporation which successfully issued its IPO in July.

Must we choose either private storage or public donation? In truth, the boundary between the two is not exactly distinct.

BabyBanks, which champions the combined benefits of donation and storage, is a private institution; yet it offers free matching for those in need of a cord blood transplant. Once a match is found, the company will ask the cord blood's owner if he is willing to donate it. If so, not only is the entire storage fee returned to the original donor; free storage is also given to the next baby, and the company gives the original donor a promise of priority matching consideration if needed.

"Our greatest competitor is the garbage can," says Bionet chairman Chris Tsai. Storage and donation are both good for oneself and for others, but over 90% of the time cord blood is neither stored nor donated; instead it's tossed into the waste bin. This is something we need to work on in the future.

In April, BabyBanks headed Taiwan's first case in which stored cord blood was donated to save a life.

The wife of Liu Min-tse had a congenital heart disease, and so the couple were particularly risk conscious. When their two sons were born, their cord blood was stored in case of later need. But when the blood bank informed them that the cord blood of their younger son Chien-an was a match for a three-year-old girl surnamed Yeh who was suffering from Cooley's anemia, the couple agreed to donate Chien-an's cord blood.

Wu Kang-hsi, the hematology-oncology physician at the China Medical University Hospital who performed little Miss Yeh's cord blood transplant, states that the hematopoietic stem cells performed their function after Chien-an's cord blood was injected into her body. Her type B blood transformed into Chien-an's type O blood, and she escaped the nightmare of daily shots of iron chelating agent and lifelong blood transfusions.

"That's great!" said Liu, describing in two simple words his feelings about the lifesaving results of his cord blood donation. This 32-year-old father admitted that he had some reservations at first, but his wife said magnanimously, "Let's donate it! What's there to think about?"

The Lius and the Yehs, one family from the north and one from central Taiwan, were two households that had never crossed paths. But a bag of cord blood built an affinity between them. Liu's wife feels as if she has gained a daughter, and this year at the Mid-Autumn Festival the Yehs sent the Lius a box of moon cakes as an expression of thanks, while the Lius plan to go to Taichung to visit little Miss Yeh.

"The unknowns in medicine far outnumber the knowns. Nobody knows what future technology will be like. But even if we don't use it ourselves, if we can help others by donating it to them, that's worth encouraging," says Lin. Neighboring Japan is mobilizing its national forces in this effort, building public blood banks and encouraging parents to donate their children's cord blood to help others in need.

Arranged by BabyBanks, cord blood donor Chien-an (center left) and little Miss Yeh, who suffers from serious Cooley's anemia, are enjoying a visit with each other. The two families, who had never met before, have formed an insoluble bond thanks to a bag of blood. Pictured to the right is Chris Tsai, chairman of Bionet, which owns BabyBanks.

Fairness and equity in healthcare

Taiwan is five to seven years behind other countries when it comes to cord blood transplanting, with a low initial success rate in human trials. But Lin points out that firstly, since 2000, higher standards of genetic matching have been required, and he hopes to achieve a five-sixths match rate; and secondly, advances in viral diagnostic techniques have allowed post-transplant infection to be detected early. Also, the newest antiviral and anti-rejection drugs have fewer side effects, plus follow-up care has improved greatly. As a result, the success rate of cord blood transplants in Taiwan has risen to 60%.

"After many attempts we know that the closer the match, the better it is. But we can't assume the worst won't happen," says Lin. If all six HLA regions of the chromosome match, the chance of rejection is one in four, whereas risking a transplant in which only three or four of the regions match is tantamount to "legal homicide."

On top of this, cord blood is a scarce resource. The risks and limitations involved in transplanting have yet to be solved, so it is worth asking whether the medical community should cut corners for the sake of time, how to weigh healthcare advancement versus patient rights, and how to achieve maximum results from minimal resources.

"Healthcare needs to be fair and equitable," says Lin. Lowering morbidity rates, mortality rates and healthcare risk will prevent patients from becoming impoverished due to illness and allow them to live better lives. This should be a priority consideration of doctors. With Cooley's anemia, for instance, which is better? A lifelong regimen of shots and transfusions? Or a cord blood transplant? Opinions may vary according to person and location.

In the past, Cooley's anemia sufferers needed daily shots of iron chelating agent and a monthly blood transfusion; nowadays the shots have been replaced by oral medication, greatly reducing the disruptions in the patient's life. But though one cord blood transplant can solve this problem forever, the patient still needs to take anti-rejection drugs for the rest of his life. Of the two options, research still needs to be done on which has the less serious side effects, which offers a better quality of life and which is more economic in terms of healthcare costs.

8. Storage in liquid nitrogen at -196oC

Forewarned is forearmed

Current stem cell research is proceeding vigorously, and researchers are preparing for the battles to come with great expectations. Yet will the results be like that of the "gene therapy" of some years ago, which created waves in the medical community and which patients eagerly hoped for, but which after repeated failures on the verge of success, has become increasingly restrained and has gradually faded from the public consciousness?

Current statistics on cord blood banks show that the usage ratio for cord blood is very low, estimated at one in 20,000. The ratio for using one's own cord blood is even lower, and such storage is for the most part for peace of mind.

"The rate for using one's own cord blood is practically zero," says Lin candidly. Autologous cord blood can save the life of a very young child suffering from a grave illness, but once the child's body weight passes 30 kg, the stem cell count in the cord blood is not enough to save his life.

But some people are placing hope in the future. Perhaps one day, stem cells from the placenta and other tissues can be harvested for their hyperplasia traits. Then cell count will no longer be a problem.

"Professional tilers leave a number of tiles with the customer in case they're needed for repair in the future. But what about human life? No matter how much money you have, you can't fight death," says Chang.

In 1995 there was a tragic incident involving radiation in a classroom at Yungchun Elementary School. In 2000, after four students from the same class died from blood cancer, a fifth student, surnamed Hsieh, was stricken with leukemia, and died waiting for a bone marrow match. "Several cord banks had opened around Taiwan in 1999 in hopes that such a painful tragedy would never happen again once the idea of storing cord blood became commonplace," says Chang with a sigh.

At the current stage in research, cord blood is not yet all-powerful, but as medical science advances, maybe one day we won't be able to do without it.

Tzu Chi Stem Cells Center

http://www2.tzuchi.org.tw/tc-marrow/html/cord.htm

Information line: (03) 8561825 ext. 3359 or 3707

Taiwan Blood Services Foundation

http://www.blood.org.tw/index.php

Service line: 0800-099519

Koo Foundation Sun Yat-sen Cancer Center

http://www.kfsyscc.org/index.php?menu_id=1453

Tel.: (02) 28970011

StemCyte Inc.

http://www.stemcyte.com.tw/

Information line: 0800-808080

Umbilical cord blood Q&A

Q: What is umbilical cord blood?

A: Cord blood is blood found inside the veins of the umbilical cord and the placenta, and is collected after a baby's umbilical cord is cut but while the placenta is still inside the mother.

Q: Whose blood is cord blood? What is it used for?

A: The blood in the umbilical cord and placenta belong to the baby; it's different from the mother's blood. Since the blood contains stem cells, it can be used clinically to treat illnesses.

Q: What diseases can a cord blood transplant treat?

A: Cord blood transplants can be a substitute for bone marrow transplants, and can be used to treat over 30 blood and metabolic diseases. These include aplastic anemia, Cooley's anemia, leukemia, myelodysplastic syndrome, mucopolysaccharidosis and osteopetrosis.

Q: How much does it cost to store cord blood?

A: For a 20-year period, storage generally costs between NT$70,000 and NT$200,000. Prices differ according to storage method and category, such as twin-bag storage (for donation and self-use), storage in two locations, and whether just the blood is stored or the umbilical cord and placenta are stored as well. After 20 years, the cord blood becomes the property of the child. It has yet to be determined how this will be handled when the time comes.

新增網頁1

Although the usage rate of one's own stored cord blood is next to zero, as technology advances, more parents who have the resources will save cord blood for the future.

How much do you know about stem cell sources?

8. Storage in liquid nitrogen at -196oC

8. Storage in liquid nitrogen at -196oC

8. Storage in liquid nitrogen at -196oC

8. Storage in liquid nitrogen at -196oC