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Cord Blood Adult Stem Cells to Repair Heart Valve Defects in Babies

Forbes, November 15, 2008

Each year thousands of babies in the U.S. alone are born with defective heart valves. Now, doctors at the University Hospital of Munich are growing new heart valves from adult stem cells derived from umbilical cord blood which are designated ultimately for the replacement of such defective heart valves in the earliest stages of a newborn's life.

From umbilical cord blood that was collected at the time of birth, cardiac surgeon Ralf Sodian and his colleagues in Munich were able to isolate those stem cells that are known to differentiate into cardiac tissue. The stem cells were then frozen and stored for 12 weeks, after which they were seeded and expanded upon a biodegradable polymer scaffold in the laboratory, from which eight new heart valves were grown. Preliminary examination with electron microscopy revealed that the stem cells had integrated into the pores of the scaffolding and not only had differentiated into cardiac tissue but also exhibited characteristics of the extracellular matrix as well. The newly engineered valves were shown to contain a wide array of proteins which included 78% as much collagen as heart valves which are formed from pulmonary tissue, 67% as much elastin, and 85% as much glycosaminoglycan, which is a carbohydrate found in connective tissue. The polymer scaffolds, which provide the architectural blueprints for the structural template of the heart valves on which the stem cells are guided in their differentiation, are designed to dissolve over time, thereby leaving behind nothing but the fully formed valve, each of which was tested for functional efficacy according to variations in blood flow volume and pressure, and all of which were found to mimic naturally occurring healthy valves. The next step, which will begin in 2009, will involve implantation of the bioengineered valves into young lambs to test how the valves change in growth and function over several years. If the valves are proven to be capable of growing as the young lambs mature and age, Dr. Sodian then expects to begin offering transplantation of these heart valves into human babies who are born with heart valve defects, using autologous (in which the donor and recipient are the same person) stem cells derived from the umbilical cord blood of each newborn.

Of all congenital heart defects, valve abnormalities are among the most common. With valves that are too narrow or do not close completely with each beat of the heart, "regurgitation" of the blood can cause a number of systemic physiological problems, depending upon the severity of the defect. In extreme cases, when a valve cannot be surgically repaired, complete valve replacement is the only solution, although valves that are transplanted into babies and children typically do not grow over time as the child grows, thereby necessitating repeated operations throughout the individual's life. Additionally, replacement valves in the past have been fashioned either from human, animal or artificial material, all of which also pose a number of risks, not the least of which is immune rejection.

As Dr. Sodian explains, "The problem is, if you have to do surgery on a child, you have a relatively small heart valve and the child grows out of it, which means you have to do the surgery many times. The basic idea is to implant something living, functional, from your own cells which will integrate into the surrounding tissue with the potential to grow. Imagine you had a child with congenital heart disease and this child has to be operated on every 2 to 3 years. It's very hard for children and parents. The goal is to do surgery once that would last a lifetime. If we replace a valve in a child, they will need surgery several times in their lifetime, because they will grow out of the device, so the ultimate goal is to have a construct which is able to grow with the child and only have to do the surgery once. Earlier is better, if possible."

The field of tissue engineering in general and of heart valves in particular is still in its infancy, with various research teams around the world exploring options for growing new heart valves not only from stem cells but also from bone marrow and amniotic fluid. Within this context, the innovation and novelty of Dr. Sodian's procedure is in and of itself worthy of attention. According to AHA (American Heart Association) spokesman Dr. Russel V. Luepker, the Mayo Professor of Epidemiology and Community Health at the University of Minnesota in Minneapolis, "The whole idea of building a scaffold is a unique idea. We generally put progenitor cells in the heart and try to get them to grow muscle cells, and they're sitting in the middle of other cells. But to build a scaffold that looks like a heart valve, then hope and anticipate that the cord blood cells will take that hint and differentiate, I think is very innovative." He cautiously adds, however, "I don't think anyone has any idea if the valves would grow. One may not know until it is put into a child, and the child grows. There are obviously a lot of hurdles to overcome."

In regard to the physiological importance of even the tiniest of heart valves, Dr. Leupker explains, "The stresses on a heart valve are enormous. They have to hold the blood back with each beat. The wear and tear on them which we see with metal and plastic valves is an issue, and those are fairly hard substances." As Dr. Sodian adds, "Tissue engineering provides the prospect of an ideal heart valve substitute that lasts throughout the patient's lifetime and has the potential to grow with the recipient and to change shape as needed. We showed that it is possible to do this with human cells."

Stem cells derived from umbilical cord blood are known to be among the most versatile of all adult stem cells, having already been demonstrated to differentiate into a wide variety of tissue types, including cardiac tissue which is one of the most highly specialized and complex of all human bodily tissues since it is both muscular and electrical in nature. Additionally, stem cells derived from umbilical cord blood are ethically noncontroversial, since the destruction of an embryo is not required for the derivation of such stem cells.

In what is known as a concept study, Dr. Sodian and his colleagues reported the results of their newly pioneered procedure today at the annual meeting of the American Heart Association in New Orleans.



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