Cord Blood May Help Repair Children's Heart Defects
Stem cells from umbilical cord blood may provide the raw material to repair the hearts of thousands of babies born each year with defective heart valves, according to data presented at last week's American Heart Association annual meeting.
Cardiologists from the University Hospital of Munich report they are about five years away from transplanting new heart valves into children with heart defects, made from the children's own cord blood.(1)
Congenital heart defects - or problems with the heart's structure that are present at birth - are the most common type of major birth defect.(2) In children with heart valve abnormalities, the valves do not fully open or close and impede the flow of blood.(3) While surgeons can transplant new valves from donors or from artificial material, these valves won't grow as the children do, meaning these individuals will require repeated operations to provide them with new, larger valves, said Dr. Ralf Sodian, the cardiac surgeon who led the research.(1)
Cardiologists from the University Hospital of Munich report they are about five years away from transplanting new heart valves into children with heart defects, made from the children's own cord blood.(1)
Congenital heart defects - or problems with the heart's structure that are present at birth - are the most common type of major birth defect.(2) In children with heart valve abnormalities, the valves do not fully open or close and impede the flow of blood.(3) While surgeons can transplant new valves from donors or from artificial material, these valves won't grow as the children do, meaning these individuals will require repeated operations to provide them with new, larger valves, said Dr. Ralf Sodian, the cardiac surgeon who led the research.(1)
"Tissue-engineered heart valve generated from human marrow stromal cells from a separate pre-clinical study. (Hoerstrup et al.)"
Replacement heart valves made from the child's own cord blood stem cells would theoretically grow with the child and change shape as needed, significantly reducing the number of surgeries necessary for these patients.
In this study, the cord blood stem cells were seeded onto biodegradable heart valve scaffolds and grown in the laboratory. The cells formed a tissue layer around the scaffolding and further tests showed the engineered cells formed viable heart tissue. When their ability to handle blood flow and pressure were tested, the valves created from cord blood stem cells showed capabilities similar to natural heart valves.(4)
Similar results from a pre-clinical study showed cord blood endothelial stem cells demonstrated excellent growth potential for tissue-engineered vascular grafts that could replace human heart defects.(5)
The research presented this week - as well as those pre-clinical findings - offer a compelling reason why parents with a child diagnosed intrauterinely with congenital defects should consider preserving their child's cord blood, since it may offer a treatment option in the future.
In this study, the cord blood stem cells were seeded onto biodegradable heart valve scaffolds and grown in the laboratory. The cells formed a tissue layer around the scaffolding and further tests showed the engineered cells formed viable heart tissue. When their ability to handle blood flow and pressure were tested, the valves created from cord blood stem cells showed capabilities similar to natural heart valves.(4)
Similar results from a pre-clinical study showed cord blood endothelial stem cells demonstrated excellent growth potential for tissue-engineered vascular grafts that could replace human heart defects.(5)
The research presented this week - as well as those pre-clinical findings - offer a compelling reason why parents with a child diagnosed intrauterinely with congenital defects should consider preserving their child's cord blood, since it may offer a treatment option in the future.
About Cardiovascular Disease
Cardiovascular disease is the leading cause of death for both men and women in the U.S. Approximately one million people die of cardiovascular disease annually despite medical intervention, with coronary artery disease claiming 50 percent of those lives.(6) Although heart disease impacts an older population whose heart muscle, arteries and pumping function have deteriorated over time, heart ailments also strike the very young. According to the National Institutes of Health, congenital heart disease is responsible for more deaths in the first year of life than any other birth defect.(7)
To date, there is no proven "off-the-shelf" therapy to repair or regenerate the heart after acute myocardial infarction (heart attack) or congestive heart failure. Because heart cells have a limited capacity to regenerate, researchers are exploring potential therapies using various stem cell sources to repair or replace damaged tissue including vascular endothelial cells, which form the inner lining of new blood vessels, and cardiomyocytes, the heart muscle cells that contract to pump blood into and out of the heart.(8)
To date, there is no proven "off-the-shelf" therapy to repair or regenerate the heart after acute myocardial infarction (heart attack) or congestive heart failure. Because heart cells have a limited capacity to regenerate, researchers are exploring potential therapies using various stem cell sources to repair or replace damaged tissue including vascular endothelial cells, which form the inner lining of new blood vessels, and cardiomyocytes, the heart muscle cells that contract to pump blood into and out of the heart.(8)
About Cardiovascular Disease and Cord Blood
The stem cells found in a newborn's umbilical cord blood are one type of stem cell holding great promise in cardiovascular repair.
Stem cells from cord blood may have an advantage over those found in bone marrow or peripheral blood because they are immunologically "younger" and appear to be more versatile. They also demonstrate an important characteristic with embryonic stem cells: they are able to differentiate into nearly all cell types in the body. However, cord blood stem cells offer important advantages: 1)they do this in a safe and controlled manner; 2)they have been used in clinical practice to treat humans for more than 20 years; and 3)there is no controversy involved in their collection.
Researchers are noting several positive observations in pre-clinical animal studies. Thus far, in animal models, cord blood stem cells have shown the ability to selectively migrate to injured cardiac tissue, improve vascular function and blood flow at the site of injury, and improve overall heart function.(6)
Stem cells from cord blood may have an advantage over those found in bone marrow or peripheral blood because they are immunologically "younger" and appear to be more versatile. They also demonstrate an important characteristic with embryonic stem cells: they are able to differentiate into nearly all cell types in the body. However, cord blood stem cells offer important advantages: 1)they do this in a safe and controlled manner; 2)they have been used in clinical practice to treat humans for more than 20 years; and 3)there is no controversy involved in their collection.
Researchers are noting several positive observations in pre-clinical animal studies. Thus far, in animal models, cord blood stem cells have shown the ability to selectively migrate to injured cardiac tissue, improve vascular function and blood flow at the site of injury, and improve overall heart function.(6)
Repairing Blood Vessels and Improving Ventricular Function
The heart demands a large volume of blood flow in order to bring nutrients and oxygen to the muscle tissue after it has been damaged. Research demonstrates that cord blood stem cells are capable of giving rise to vascular endothelial-like cells, which are believed to aid in the repair of heart tissue damage due to myocardial infarction.
Several pre-clinical studies of induced myocardial infarction in rats have shown that cord blood stem cells have the ability to:
Several pre-clinical studies of induced myocardial infarction in rats have shown that cord blood stem cells have the ability to:
- Migrate and engraft to damaged heart muscle (9,10)
- Contribute to the formation and proliferation of new blood vessels (9,11)
- Improve left ventricular remodeling, structural damage and function (12)
- Decrease the size of infarction (13)
These animal studies may lay the foundation for future human clinical trials testing cord blood stem cell treatment for patients with heart damage due to myocardial infarction.
Cardiomyocytes and Cord Blood: In Vitro Studies Show Promise
Permanent loss of cardiomyocytes (heart muscle cells) and the formation of scar tissue following a heart attack result in irreversible damage to cardiac function. Human cord blood contains several different types of stem cells including hematopoietic, endothelial and mesenchymal stem cells. Although still in early stages, four in vitro studies have shown that under certain treatment conditions, cord blood mesenchymal stem cells differentiate into cardiomyocyte-like cells (14,15,16,17) and were able to induce regeneration of healthy cells from damaged cardiomyocytes.(17) This suggests that cord blood stem cells have a high potential to differentiate into cardiomyocytes and aid the regeneration of cardiomyocytes lost due to heart damage.
Advances in Peripheral Vascular Disease
The ability of cord blood stem cells to become vascular endothelial-like cells and thus, blood vessels, indicates they will likely have potential applications beyond the heart.
Peripheral vascular disease (PVD) is a restriction of blood flow outside of the heart usually occurring in the legs and arms. Restricted blood flow is caused by blood vessel narrowing from fatty plaque formation on vessel walls (atherosclerosis) or blockage due to blood clots. If the blockage is severe enough, tissue death can occur. If left untreated, the limb may need to be amputated.(18)
In animal models, cord blood stem cells have been able to significantly reverse the effects of ischemia, or loss of blood flow in the blood vessels. In models of hind limb ischemia, transplantation of cord blood stem cells appeared to reverse surgery-induced ischemia resulting in limb salvage. (19,20) These observations may lead to future human clinical trials using cord blood stem cells to treat patients with peripheral vascular disease.
Peripheral vascular disease (PVD) is a restriction of blood flow outside of the heart usually occurring in the legs and arms. Restricted blood flow is caused by blood vessel narrowing from fatty plaque formation on vessel walls (atherosclerosis) or blockage due to blood clots. If the blockage is severe enough, tissue death can occur. If left untreated, the limb may need to be amputated.(18)
In animal models, cord blood stem cells have been able to significantly reverse the effects of ischemia, or loss of blood flow in the blood vessels. In models of hind limb ischemia, transplantation of cord blood stem cells appeared to reverse surgery-induced ischemia resulting in limb salvage. (19,20) These observations may lead to future human clinical trials using cord blood stem cells to treat patients with peripheral vascular disease.
The Future of Cord Blood Stem Cell Cardiac Therapy
As a next step to the research presented at the American Heart Association meeting, the study investigators plan to begin experiments next year to test their procedure in animal models. They will implant the heart valves made from cord blood into the hearts of young lambs, observing their ability to grow and function over time.(1)
The growing library of research on cardiac repair suggests an infant's own cord blood could prove to be a valuable treatment option not just for treating a congenital heart defect, but perhaps later in life if the individual experiences a sudden and serious heart attack.
The growing library of research on cardiac repair suggests an infant's own cord blood could prove to be a valuable treatment option not just for treating a congenital heart defect, but perhaps later in life if the individual experiences a sudden and serious heart attack.
1Waters R. Cord Blood Stem Cells May Help Repair Babies' Heart Defects. Bloomberg. November 10, 2008. http://www.bloomberg.com/apps/news?pid=20601124&sid=aWRs4Rf8yvjY&refer=home. Accessed November 2008.
2Centers for Disease Control and Prevention. About Heart Disease Page. http://www.cdc.gov/HeartDisease/about.htm. Accessed April 2008. 3Arkansas Children's Hospital. The Heart Center. Heart Conditions, Diagnosis and Treatment. http://www.pediatric-cardiology.com/Heart_Health/heart_health.asp. Accessed November 2008.
4American Heart Association Press Release. Umbilical cord blood may help build new heart valves. http://americanheart.mediaroom.com/index.php?s=43&item=548. Accessed November 2008.
5Schmidt D, Breymann C, Weber A, Guenter CI, Neuenschwander S, Zund G, Turina M, Hoerstrup SP. Umbilical cord blood derived endothelial progenitor cells for tissue engineering of vascular grafts. Ann Thorac Surg. 2004 Dec;78(6):2094-8.
6Harris DT, Badowski M, Ahmad N, Gaballa MA. The potential of cord blood stem cells for use in regenerative medicine. Expert Opinion on Biological Therapy. 2007;7(9):1311-1322.
7U.S. National Library of Medicine and National Institutes of Health. Medline Plus. Congenital Heart Disease page. http://www.nlm.nih.gov/medlineplus/ency/article/001114.htm. Accessed January 2008.
8National Institutes of Health. Stem Cell Information Page. http://stemcells.nih.gov/info/scireport/chapter9.asp. Accessed January 2008.
9Ma N, Stamm C, Kaminski A, Li W, et al. Human cord blood cells induce angiogenesis following myocardial infarction in NOD/scid-mice. Cardiovascular Research. 2005;66(1):45-54.
10Hu CH, Wu GF, Wang XO et al. Transplanted human umbilical cord blood mononuclear cells improve left ventricular function through angiogenesis in myocardial infarction. Chin Med J (Engl). 2006;119(18):1499-506.
11Ma N. Ladilov Y, Kaminski A, Piechaczek C. Stamm C. Umbilical cord blood cell transplantation for myocardial regeneration. Transplant proc. 2005;38(3):771-3.
12Leor J, Guetta E, Feinberg MS et al. Human umbilical cord blood-derived CD133+ cells enhance function and repair of the infarcted myocardium. Stem Cells. 2006;24(3):772-80.
13Henning RJ, Abu-Ali H, Balis JU, Morgan MB, Willing AE, Sanberg PR. Human umbilical cord blood mononuclear cells for the treatment of acute myocardial infarction. Cell Transplant. 2004;13(7-8):729-39.
14Cheng F, Zou P, Handong Y. Induced differentiation of human cord blood mesenchymal stem/progenitor cells into cardiomyocyte-like cells in vitro. J Huazong Univ Sci and Tech. 2003;23(2):154-157.
15Nishiyama N, Miyoshi S, Hida N, et al. The significant cardiomyogenic potential of human umbilical cord blood-derived mesenchymal stem cells in vitro. Stem Cells. 2007;25(8):2017-24.
16Bonanno G, Mariotti A, Procoli A, et al. Human cord blood CD133+ cells immunoselected by a clinical-grade apparatus differentiate in vitro into endothelial- and cardiomyocyte-like cells. Transfusion. 2007;47(2):280-9.
17Yamada Y, Yokoyama S, Fukuda N, et al. A novel approach for myocardial regeneration with educated cord blood cells cocultured with cells from brown adipose tissue. Biochem Biophys Res Commun. 2007;353(1):182-8.
18U.S. National Library of Medicine and National Institutes of Health. Medline Plus. Peripheral Vascular Disease page. http://www.nlm.nih.gov/medlineplus/peripheralvasculardiseases.html. Accessed January 2008.
19Ikeda Y, Noboru F, Wada M, Matsumoto T, Satomi A, Yokoyama SI, Saito S, Masumoto K, Katsuo K, Mugishima H. Development of angiogenic cell and gene therapy by transplantation of umbilical cord blood with vascular endothelial growth factor gene. Hypertens Res. 2004;27(2):119-128.
20Cho S-W, Gwak S-J, Kang S-W, et al. Enhancement of angiogenic efficacy of human cord blood cell transplantation. Tissue Eng. 2006;12(6):1651-1661.
2Centers for Disease Control and Prevention. About Heart Disease Page. http://www.cdc.gov/HeartDisease/about.htm. Accessed April 2008. 3Arkansas Children's Hospital. The Heart Center. Heart Conditions, Diagnosis and Treatment. http://www.pediatric-cardiology.com/Heart_Health/heart_health.asp. Accessed November 2008.
4American Heart Association Press Release. Umbilical cord blood may help build new heart valves. http://americanheart.mediaroom.com/index.php?s=43&item=548. Accessed November 2008.
5Schmidt D, Breymann C, Weber A, Guenter CI, Neuenschwander S, Zund G, Turina M, Hoerstrup SP. Umbilical cord blood derived endothelial progenitor cells for tissue engineering of vascular grafts. Ann Thorac Surg. 2004 Dec;78(6):2094-8.
6Harris DT, Badowski M, Ahmad N, Gaballa MA. The potential of cord blood stem cells for use in regenerative medicine. Expert Opinion on Biological Therapy. 2007;7(9):1311-1322.
7U.S. National Library of Medicine and National Institutes of Health. Medline Plus. Congenital Heart Disease page. http://www.nlm.nih.gov/medlineplus/ency/article/001114.htm. Accessed January 2008.
8National Institutes of Health. Stem Cell Information Page. http://stemcells.nih.gov/info/scireport/chapter9.asp. Accessed January 2008.
9Ma N, Stamm C, Kaminski A, Li W, et al. Human cord blood cells induce angiogenesis following myocardial infarction in NOD/scid-mice. Cardiovascular Research. 2005;66(1):45-54.
10Hu CH, Wu GF, Wang XO et al. Transplanted human umbilical cord blood mononuclear cells improve left ventricular function through angiogenesis in myocardial infarction. Chin Med J (Engl). 2006;119(18):1499-506.
11Ma N. Ladilov Y, Kaminski A, Piechaczek C. Stamm C. Umbilical cord blood cell transplantation for myocardial regeneration. Transplant proc. 2005;38(3):771-3.
12Leor J, Guetta E, Feinberg MS et al. Human umbilical cord blood-derived CD133+ cells enhance function and repair of the infarcted myocardium. Stem Cells. 2006;24(3):772-80.
13Henning RJ, Abu-Ali H, Balis JU, Morgan MB, Willing AE, Sanberg PR. Human umbilical cord blood mononuclear cells for the treatment of acute myocardial infarction. Cell Transplant. 2004;13(7-8):729-39.
14Cheng F, Zou P, Handong Y. Induced differentiation of human cord blood mesenchymal stem/progenitor cells into cardiomyocyte-like cells in vitro. J Huazong Univ Sci and Tech. 2003;23(2):154-157.
15Nishiyama N, Miyoshi S, Hida N, et al. The significant cardiomyogenic potential of human umbilical cord blood-derived mesenchymal stem cells in vitro. Stem Cells. 2007;25(8):2017-24.
16Bonanno G, Mariotti A, Procoli A, et al. Human cord blood CD133+ cells immunoselected by a clinical-grade apparatus differentiate in vitro into endothelial- and cardiomyocyte-like cells. Transfusion. 2007;47(2):280-9.
17Yamada Y, Yokoyama S, Fukuda N, et al. A novel approach for myocardial regeneration with educated cord blood cells cocultured with cells from brown adipose tissue. Biochem Biophys Res Commun. 2007;353(1):182-8.
18U.S. National Library of Medicine and National Institutes of Health. Medline Plus. Peripheral Vascular Disease page. http://www.nlm.nih.gov/medlineplus/peripheralvasculardiseases.html. Accessed January 2008.
19Ikeda Y, Noboru F, Wada M, Matsumoto T, Satomi A, Yokoyama SI, Saito S, Masumoto K, Katsuo K, Mugishima H. Development of angiogenic cell and gene therapy by transplantation of umbilical cord blood with vascular endothelial growth factor gene. Hypertens Res. 2004;27(2):119-128.
20Cho S-W, Gwak S-J, Kang S-W, et al. Enhancement of angiogenic efficacy of human cord blood cell transplantation. Tissue Eng. 2006;12(6):1651-1661.
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