Scientists at the Duke Comprehensive Cancer Center say they have proven for the first time that stem cells in umbilical cord blood can transform themselves into the kind needed to stop further damage in heart tissue.

While the use of stem cells may seem controversial to some, the type of research conducted at Duke only involves blood from the umbilical cord, which once cut from the baby, serves no other purpose.

“The use of stem cells from umbilical cord blood is not controversial,” explains Becky Levine, a spokeswoman for Duke Medical Center, “because the cord blood is taken with consent from the mother from newborn babies and would normally have been discarded anyway.”

Cord blood has long been used by physicians at Duke to correct heart, brain and liver defects in children with rare metabolic diseases. But until now they lacked the molecular evidence to prove that cord blood stem cells were the root of a cure.

Now, the Duke team has dissected heart tissue to confirm the presence of donor stem cells in heart tissue. Moreover, they showed that donor stem cells had differentiated into heart muscle cells called myocytes, which then produced the critical enzyme needed to halt the progressive heart damage, said Kirsten Crapnell, a research fellow at Duke.

Crapnell recently presented the Durham-based team’s findings at the International Bone Marrow Transplantation Registry meeting in Orlando.

“We’ve had convincing clinical evidence that stem cells from umbilical cord blood extended much farther than the blood-forming and immune systems, and that they can differentiate themselves into brain, heart, liver and bone cells,” said Joanne Kurtzberg, director of the Duke Pediatric Bone Marrow and Stem Cell Transplant Program. “But now we have examined heart tissue on a cellular level and proven that donor cells are not only present in heart tissue, but they have become heart muscle cells.”

To validate the stem cells’ activities, Crapnell dissected and analyzed heart tissue from a 4-year-old boy whose transplant was successful, but who later died of an infection before his immune system was strong enough to fight it. The boy had suffered from a rare metabolic disease called Sanfilippo Syndrome B, in which the body is missing a critical enzyme needed to break down complex sugars in various cells. As sugar byproducts accumulate in vital organs such as the liver, heart and brain, cells are damaged and die.

Duke physicians had observed that children with these rare metabolic diseases tended to regain organ function more rapidly when given cord blood rather than traditional bone marrow. They theorized that cord blood stem cells, being less mature than stem cells in adult bone marrow, could more easily adapt to their new surroundings and respond to signals that differentiate them into the needed kind of cell.

Crapnell proved the presence of donor stem cells in the young boy’s heart by searching for aberrant female stem cells from his baby girl donor amid his largely male heart cells. She used stains to label heart cells as either male or female and to test for cell surface “markers” that indicate what type of cell it is. The first stain had an affinity for troponin, a protein on the surface of heart cells. The second stain had an affinity for myosin, a protein on the surface of muscle cells.

She found that, although few in number, the female heart cells were clearly illuminated amid a larger pool of male myocytes. Just a few donor stem cells are enough to provide a wide swath of damaged tissue with the enzyme necessary to restore function, Crapnell and other researchers believe.

Brain cell transformation also occurs

The same phenomenon is likely at work in brain tissue as well, said Jennifer Hall, another research fellow at Duke who is also presenting at the International Bone Marrow Transplantation Registry meeting in Orlando.

Research shows that cord blood transplants appear to halt or slow the progressive brain damage that is caused by metabolic diseases such as Sanfilippo. Yet time is lost as the stem cells make their way from the bloodstream into the brain, where they eventually differentiate into the needed types of brain cells, potentially causing children to miss a critical therapeutic window of treatment.

Hall tested the potential of hematopoietic stem cells to differentiate inside a test tube into specific kinds of brain cells called oligodendrocytes that are targeted for destruction in children with metabolic diseases. She cultured a unit of cord blood stem cells together with growth factors, hormones and other compounds that direct stem cells toward the oligodendrocyte lineage. One month later, Hall analyzed the cells under a microscope and found that 60 percent of them appeared to resemble cells of the same lineage.

She validated her observations by staining the cells with various antibodies that only bind to and illuminate proteins unique to oligodendrocytes precursor cells and ones with antibodies for a host of other cell types. The presence of unique proteins in a given cell confirms that it is actively producing that protein, not just that its genetic code is capable of doing so, said Hall, and in this case, the oligodendrocytes were producing the needed protein or enzyme.

“The therapeutic goal is to rapidly produce oligodendrocytes in the lab, and then infuse them into patients soon after transplant,” said Hall. “Delivering cells directly to the brain could hasten engraftment of the cells and could ultimately result in repairing of neurologic tissue.”

Hall said the potential also exists for repairing spinal cord injuries and multiple sclerosis, which … like the metabolic “leukodystrophies” (brain degeneration)… result from imperfect growth of the myelin sheath that coats nerve cells.

Predicting infectious disease risk, too

Transplant physicians at the Duke Comprehensive Cancer Center also have identified several risk factors that make certain children more likely than others to die of viral infections after receiving umbilical cord blood transplants to cure their deadly cancers, immune diseases and rare metabolic disorders.

Children are at highest risk of infection during the first 100 days after transplant, when their new immune system struggles to take hold. As a result, almost half of all deaths after cord blood transplantation are caused by infections, and among those, viruses are by far the most common. The children who live, however, are typically cured of their deadly cancers, immune disorders and rare metabolic diseases.

The Duke team has already applied their findings in the laboratory toward strengthening cord blood’s ability to wage an immune response. Doctors ultimately plan to infuse these bolstered immune cells into transplant patients to more effectively fend off opportunistic infections, said Paul Szabolcs, assistant professor of pediatrics and immunology at the Duke Pediatric Bone Marrow and Stem Cell Transplant Program.

Szabolcs also was recently in Orlando, presenting the findings of his study at the International Bone Marrow Transplantation Registry meeting.

In an effort to predict a child’s risk of infection, Szabolcs studied the immune status of 102 children at the Duke Pediatric Bone Marrow and Stem Cell program. He looked for immune system differences that could explain why some children succumb to infections and die while others do not.

“Our goal was to predict which children would be at greatest risk for infection so that, in the near future, we can reinforce a child’s immune response immediately following their transplant,” said Szabolcs. “Until now, we haven’t understood what factors predict for opportunistic infections that claim the lives of certain patients.”

Duke Pediatric Bone Marrow and Stem Cell Transplant Program:

International Bone Marrow Transplantation Registry: