The St. Louis Cord Blood Bank at Cardinal Glennon has become the second-largest, and possibly most active, unit of its kind in the world. Cord blood stem cells from St. Louis have saved the lives of hundreds of patients in North America, South America, Europe, Australia and the Middle East. Cord blood could become even more valuable in the future.

A few weeks before Alyssa Mikesell was born, her mom was asked about donating her umbilical cord to the St. Louis Cord Blood Bank at Cardinal Glennon Children’s Hospital. When the obstetrician explained that the process would be simple and that someone’s life might be saved as a result, mom agreed immediately.

“There were no down-sides to donating and it was a great opportunity to possibly give life to another person,” said Christine Mikesell of Wildwood, Missouri.

After Alyssa was born on November 20 last year, her obstetrician, David Weinstein, M.D., spent a few minutes withdrawing the blood from the umbilical cord. A delivery room nurse assisted him in transferring the blood to a collection bag and calling the cord blood bank to dispatch a courier. Although Alyssa was just minutes old, she already had given one of the best gifts ever.

“Alyssa is wonderful. She couldn’t be doing better,” Mrs. Mikesell said of her first child. “After having her and realizing how wonderful she is, possibly giving someone else the gift of life was the most precious thing in the world.”

A MIDWESTERN MIRACLE

The six-year-old St. Louis Cord Blood Bank has grown rapidly to become the world’s second-largest repository of cord blood. Through the end of 2001, the bank had saved 6,956 cord blood units and exported 372 units to 84 medical centers in 18 countries and 28 in the United States. Units from the bank have been used in 33 transplants performed for patients at Cardinal Glennon.

The St. Louis bank may have provided about half of the cord blood units transplanted globally in 2001.

Cord blood is one of three sources of hematopoetic stem cells that can be used in the treatment of some cancers, immune deficiencies and genetic metabolic and blood disorders. The first stem cell transplant was performed in 1968 with bone marrow, which has remained the most common source, at least for adults. Stem cells also may be collected from the blood stream of the patient or a donor.

Hematopoetic stem cells, which continually replicate to produce new blood cells, have been used in cancer treatments because the chemotherapy used to kill cancer cells also kills normal cells in the body, including the blood-forming cells in the bone marrow. After the patient has finished chemotherapy treatments, replacement stem cells are transplanted to replace the absent blood system.

Historically, the chances of finding a good blood match from potential peripheral blood or bone marrow donors have been small, and cord blood has provided another option for making a match. Knowledge gained in recent years suggests that the younger cells in cord blood also may pose a reduced risk of a potentially life-threatening complication called “graft versus host disease.”

“The chances of finding someone who is a perfect stem cell match is probably less than one out of 25,000,” said Dennis M. O’Connor, M.D., director of the division of hematology/oncology at Glennon and professor of pediatrics at St. Louis University. “The more cord bloods that are donated and the more people who are registered as bone marrow donors, the better the chances we have of taking care of patients.”

Since 1996, the St. Louis Cord Blood Bank has gained stature as one of the world’s leading cord blood resources. Such a development might only have been possible in a Midwestern city such as St. Louis, which is large enough to host a major clinical and research medical center but not so large to lose its small-town compassion and altruism.

The cord blood bank could not have opened without the generosity of mothers donating umbilical cords, healthcare professionals collecting them and community supporters providing the funds needed to operate the bank. “This is truly a community program, because it would not be so successful without the moms donating and the obstetricians, hospital staffs and labor and delivery nurses doing the collecting,” said Kathy Mueckl, R.N., nurse coordinator of the bank’s “First Gift” program. “Everybody donates their time without charge. Without that community support we could not function.” Cord blood is donated to the bank through 29 Missouri and Illinois hospitals operated by a variety of health care systems. Initially, many more hospitals and obstetricians generously agreed to participate in the First Gift program but the bank found that it was not possible to arrange cost-effective and timely courier deliveries from all of them, Mueckl said.

Each year the bank bestows an honorary “Golden Placenta” award on the obstetrician responsible for the largest number of donations. Weinstein, whose practice is based in west St. Louis County, received the award in 1996 and 1997 and continues to be one of the program’s biggest supporters.

“This program can save lives, and it’s so easy to do with just a little effort on my part,” Weinstein said. “I tell my patients they can save a life with something that otherwise is thrown away. The response is overwhelmingly positive. At a time when parents are bringing their own babies into the world, it is such a joyful and happy experience. Being able to share some of that joy by saving an existing life is a wonderful thing.”

Nancy Bucy, D.O., of Lake St. Louis, Missouri, received the Golden Placenta in 1998. Lisa Jabusch, M.D., of Alton, Illinois, was the honoree in 1999 and 2000.

“The advances that have been made in the few years I have supported the program have been wonderful,” Jabusch said. “The collection process just takes two to three minutes. I clean the cord with alcohol and betadine, stick a needle in the cord, drain the blood into a bag and hand it off to a nurse. It is so exciting – besides bringing a new life into the world, I also could be saving a life with two minutes of work.”

GAINING EXPERIENCE WITH CORD BLOOD

Exceptional success rates have been tallied in the few years that cord blood has been used as an alternative source of stem cells, said Michael Creer, M.D., director of the St. Louis Cord Blood Bank and professor of pathology at St. Louis University.

“We are very excited about the outcomes for our transplants. The survival rate is almost 70 percent for recipients under the age of 17,” he said.

It initially was believed that a cord blood unit contained only enough stem cells to transplant smaller children, but doctors have gradually worked through larger children, teenagers and small adults as they gained confidence in the procedure. Some medical centers are attempting to treat larger adults by combining two cord blood units despite the fact that they are not exact blood-type matches. The largest person who has received a cord blood product from the St. Louis bank weighed about 270 pounds.

“In adults the overall five-year survival rate is 50 to 60 percent using cords from our bank. These patients are potentially cured of their diseases,” Creer said. “This is the last resort for many of them. Often we are using cord blood to transplant people who have failed other treatments and have suffered from a recurrence of the disease for which they were initially transplanted. We are seeing cord blood introduced as an option earlier and earlier in adults. As we gain more experience and begin seeing cord blood used as a first option, we believe the outcomes in adults will become significantly better.” Also, Creer said, only 20 percent of patients who receive cord blood stem cells develop severe graft versus host disease compared with 50 to 70 percent of patients given a bone marrow or peripheral blood stem cell transplant from an adult donor.

Although stem cell transplants have saved thousands of lives over the past three decades, researchers have yet to determine exactly which cells in blood and bone marrow are stem cells. A protein marker called “CD34” is used to measure the number of cells in a unit that may be stem cells.

“Based on the different ways we count the cells, we only have to give one-tenth as many cord blood cells and the transplant works as well as bone marrow,” Creer said.

A GLOBAL RESOURCE

The staff of the St. Louis Cord Blood Bank has become a resource to the world’s cord blood network. They are consulted by government agencies and professional organizations developing cord blood bank operating standards and techniques. They have been visited by doctors and technicians forming new banks and have assisted medical manufacturers in developing new products needed by cord blood banks.

“Our people have been doing this a lot longer than others and have learned a lot of the tricks,” Creer said. “Some of their family members have been affected by the diseases that cord blood could treat. They have dedicated their lives to making this bank work. They have put in far more hours than they are paid for, and that has been an important factor accounting for the success of this department.”

“We are involved in developing the standards that regulate collection, banking and therapeutic use of cord blood,” said Donna Regan, MT (ASCP), SBB, quality manager of the bank. “This is still an investigative field.”

Cord blood from St. Louis has been used in 372 of the approximately 2,000 cord blood stem cell transplants that have been performed internationally. A number of the world’s cord blood banks are linked by a computer network that assists transplant centers in searching for matching stem cell types for their patients. The computer network used by the National Marrow Donor Program underwent final development testing by J. Mario Alonso III, MT (ASCP), manager of the St. Louis Cord Blood Bank.

Survival rates for patients receiving St. Louis cord blood are higher than the averages for all cord blood transplants, Creer said. From the beginning, the bank set very strict criteria for determining which cord blood units would be accepted for the expensive banking process.

“First we go by the minimum volume of cord blood in the collection bag. The biggest reason people like coming to our bank is because we do have larger units,” Alonso said. “The most important factor in survival for cord blood recipients is the number of cells that are transplanted.”

In addition to a fluid volume requirement, each unit also must pass a minimum cell-count criteria, using markers for stem cell presence, before it is processed.

“Once that has been done, we still have to do all the infectious disease-marker testing that the Red Cross does on donated blood. Kathy Mueckl also reviews the medical history questionnaires from the moms to make sure there are no risk factors that might cause us not to keep those units,” Alonso said.

The cord blood is spun in a centrifuge to separate the red cells, white cells and plasma. Only the white cells, which contain the stem cells, are banked. A cryoprotectant is added to the stem cells to prevent them from bursting when frozen. “Finally we run them through a controlled-rate freezer and put them into liquid nitrogen tanks that store them at –290 degrees Fahrenheit,” Alonso said.

It takes eight to ten hours to process six cord blood units. Many of the units that are not large enough for banking still are put to good use by being shipped to medical laboratories across the country for stem cell research.

Researchers are trying to better understand how stem cells work, how they might be expanded so that cord blood may be used to treat larger children and adults, and how the stem cells might be assisted in engrafting more quickly into recipients.

“Cardinal Glennon has done more cord blood transplants than most other institutions and the results are fantastic. We have done enough cord blood transplants to know that it is a very viable option, at least in the pediatric population,” said Michael Kelly, M.D., a St. Louis University instructor of pediatrics and a member of the division of hematology/oncology at Glennon.
“Obviously, there are a limited number of cells in a cord. We haven’t realized the full potential of cord blood transplantation yet because adults have been relatively excluded.”

Researchers have been able to expand the number of stem cells in a cord unit by growing them in culture, but so far expansion has produced colonies of matured cells rather than larger numbers of the inexperienced stem cells that help make cord blood transplants effective. As the expanded stem cells pass through generations of replication and maturation, they seem to trigger more detection by the recipient’s immune system.

“One reason that cord blood is so beneficial is that it produces less graft versus host disease,” Regan said. “After the stem cells undergo expansion, they become more mature and fight the body because they have more self-recognition. Before expansion, cord blood stem cells are naďve when it comes to mounting that kind of response.” While researchers seek a method of expanding stem cells without maturing them, they also are searching for means of helping them grow faster after they are transplanted into a patient.

Three to four weeks may pass while transplanted stem cells become fully functional after a patient has received chemotherapy to eliminate the body’s existing blood-making mechanisms, said Richard A. Cahill, M.D., a member of the hematology/oncology division at Glennon. “That is a long period of time to go without white cells. Many patients are at risk of infections after their transplants, even though we have great antibiotics, antifungals and some antivirals.”

Cahill, director of transplant services at Glennon and associate professor of pediatrics at St. Louis University, has conducted research into the role of mesenchymal cells in nurturing transplanted stem cells in their new environment. Mesenchymal cells are a subset of stem cells that can develop into other specialized cell types. Those types include cells of the bone marrow microenvironment, also known as stroma, in which stem cells replicate to produce new blood cells.

Cahill joined the Glennon staff last fall after spending four years at All Children’s Hospital and the University of Southern Florida in St. Petersburg. There he worked with Robert A. Good, M.D., Ph.D., who performed the first bone marrow transplant in 1968, and began his own research into the use of mesenchymal cells in facilitating stem cell transplants.

The bone marrow stroma nurtures blood cell production along the inner lining of the bones, so Cahill experimented with the transplantation of a small number of bone fragments along with the marrow of donors. “The stroma provides nutrients and growth factors for the stem cells. If we could expand the mesenchymal cells, we could use cords to treat bigger adult patients and facilitate engraftment in children. If we could reduce the engraftment time to two weeks from three or four weeks and reduce graft versus host disease, we could transplant and save many more patients."

Preliminary research also has found that the mesenchymal cells in cord blood have the potential to reproduce and differentiate into other types of cells, such as cartilage, bone, muscle and nerves. A considerable amount of research effort has been devoted to the use of embryonic mesenchymal cells to treat injuries and diseases of the brain, nervous system, liver, kidneys, heart and other organs. If cord blood can be proven as a viable source of mesenchymal cells for new treatments of these diseases, it might replace the controversial use of fetal tissues as a source. “When we are young, we have more mesenchymal cells and they can potentially replace damaged tissues,” Cahill said, explaining why researchers have focused on fetal tissues and cord blood as sources of them. “As we get older we have fewer and fewer of them. That’s why it takes us longer to heal.”

“The whole concept of cellular therapy is just beginning to emerge,” said Creer. “The possibilities are exciting. Experiments, that mostly have been done in animal models, show that there is potential for stem cells to actually go into sites of injury throughout the body and provide precursor cells that can replace dead cells. It appears that some of the stem cells have the
potential to develop into different kinds of cells under the appropriate conditions.”

Cellular therapies using stem cells may be used some day to treat Parkinson’s disease and other brain injuries, muscular dystrophy, damaged blood vessels, and diseases of the liver, kidneys and heart. “Ischemic heart disease is the cause of death for 40 to 60 percent of us,” Creer said.

Physicians, researchers and technicians at Glennon and St. Louis University are eager to expand their cord blood stem cell research, Creer said. “We are going to develop a lab within the bank to answer many questions. What can cord blood stem cells become? How many are present in umbilical cord blood? How can we best isolate and preserve them?

“Umbilical cord blood could be considered an alternative to the embryonic stem cell approach. Our goal is to be involved in activities designed to prove that umbilical cord blood, which is normally discarded at birth, has the same magic that you might find in embryonic stem cells and without the theologic objections to using embryonic cells.”

A GIFT FROM ST. LOUIS TO THE WORLD

Members of the St. Louis Cord Blood Bank staff regularly make presentations at national and international medical conferences. “We have become the gold standard in the field,” Regan said. "It has been humbling and encouraging at the same time. Cardinal Glennon is becoming known all over the world.”

The bank has been visited by doctors and technicians seeking guidance in establishing cord blood banks across the U.S. and Europe as well as in Canada, Israel, Korea, Australia, India, Japan, Pakistan, China and Taiwan.

“The biggest message we want to get out is that we are here because of the St. Louis community at large,” Alonso said. “In other places there are a lot of issues about the politics of ownership. Here, the community is the owner. Every mom, dad and baby who donate a cord to this bank is a part of this. Then there are the obstetricians, the labor and delivery nurses and the phlebotomists and some very wonderful people who donated their money to us. It takes everybody doing their part.

“When you think that 50 to 70 percent of the people who receive our cord blood are surviving when they had no other hope before, that is really fulfilling.”

The St. Louis Cord Blood Bank may be reached by calling 314.268.2787 or 888.453.CORD.