Origins of blood vessel cells


Indianapolis -- Researchers at the Indiana University School of Medicine have discovered how the body makes the cells that line its blood vessels, work that could someday lead to dramatic new treatments for vascular problems ranging from stroke to diabetes.

The origin of these endothelial cells, which play a vital role in the body's circulatory system and internal organs, has been uncertain. But by extracting and comparing cells from adult blood and infant umbilical cords, the IU team was able to isolate the parents -- the progenitors -- of the cells and explain how they differ from related cells.

The progenitor cells that the researchers identified are adult type stem cells, but they proliferate much like embryonic stem cells, and they can be grown in large quantities in the laboratory, said Mervin C. Yoder, M.D., Richard and Pauline Klingler professor of pediatrics and of biochemistry and molecular biology.

The research appears in the online version of Blood, the journal of the American Society of Hematology.

Endothelial cells make up the inner lining of the blood vessels in the body, as well as the capillary beds where the blood delivers its nutrients and oxygen to other cells.

The researchers found that the endothelial cells are formed in a manner similar to the blood cells carried by the circulatory system, said David A. Ingram, Jr., M.D., assistant professor of pediatrics.

The red blood cells that carry oxygen and "white" cells that make up the body's immune system are descended from a series of progressively less differentiated cells, created in a process called hematopoiesis ("hee-matt-oh-po-esis"). The source of those less differentiated cells are a relative handful of hematopoietic stem cells, found mainly in the bone marrow. Researchers have been attempting to use hematopoietic stem cells in gene therapy, hoping to correct immune disorders, certain cancers and other genetic problems by inserting genes into the stem cells. Progress has been slow, however, because hematopoietic stem cells are hard to find, difficult to grow in the laboratory and hard to modify with genes.

The endothelial progenitor cells, on the other hand, not only grew exceedingly well, but were easily modified with new genes, raising the prospects of a new gene therapy tool, Yoder said. He foresees a day -- many years in the future -- when genetically modified endothelial stems cells would help diabetes patients reverse the circulatory problems that threaten them with the loss of extremities from amputation. Or the day could come in which modified cells would be injected to quickly begin a process of blood vessel repair after a heart attack.

Previously, researchers have attempted to identify possible endothelial progenitor cells using indirect measures involving certain protein "markers" on the surfaces of cells. The Indiana University scientists, however, were able to isolate the endothelial progenitor cells directly from cord blood and grow them the laboratory. Unlike the cells previously identified in adult blood as possible endothelial progenitor cells, the cord blood progenitor cells could be grown for at least 100 new generations, forming many new colonies of cells.

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