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Researchers success in isolating hematopoietic stem cells could aid bone marrow transplantation, gene therapy.

Researchers have found a way to isolate elusive hematopoietic stem cells (HSC), a discovery that could someday alleviate blood shortages for transfusions and lead to new approaches to bone marrow transplantation and gene therapy.

"The hematopoietic stem cell (HSC) has been considered the elusive Holy Grail of hematology and immunology, said Cesare Peschle, PhD of Thomas Jefferson University in Philadelphia, PA and the Instituto Superiore di Sanita in Rome, Italy who led the multinational research team. "Now it has been found and captured by identifying the first specific and functional stem cell marker."

HSCs are 1 of 2 types of precursor blood cells, the other being hematopoietic progenitor cells. HSCs have 2 crucial abilities: to develop into any kind of blood cell and to self-renew by generating new daughter stem cells. Progenitor cells are further along in the differentiation process than HSCs. While they, too, can become red blood cells, white blood cells, and platelets unlike HSCs, progenitor cells do not have the capacity to self-perpetuate; they give rise only to more differentiated precursor cells.

Distinguishing between the two types of blood cells has proved difficult. Both are extremely uncommon, but HSCs are the rarer. For the past decade, scientists have been able to isolate undifferentiated progenitor cells using a marker on the cell known as CD34. Between 0.5-1% of bone marrow cells are hematopoietic progenitor cells carrying CD34, but only 0.1% of CD34 cells are HSCs--1 HSC per 100,000 marrow cells. What was needed was a specific marker on the cell surface of HSCs comparable to CD34 on progenitor cells.

"Once you have a marker protein for HSCs, you can theoretically raise antibodies against the marker, and then you can separate stem cells from other cell populations," explained Peschle.

The investigators found that KDR, a protein which functions as a receptor for vascular endothelial growth factor, is expressed at low levels on CD34-positive progenitor cells. Theorizing that KDR might represent a marker for HSCs, they used an antibody that recognized the KDR receptor and was capable of isolating KDR-expressing cells from other progenitors in the CD34-positive progenitor cell population. And they discovered that only HSCs--and no progenitor cells--expressed KDR.

Peschle and his colleagues now are able to determine the exact frequency of HSCs in the KDR-positive population and have used animals to evaluate the capability of KDR-positive HSCs to repopulate the bone marrow with blood cells after transplantation. The ability to manipulate these cells and induce them to self-renew and differentiate, said Peschle, eventually will allow scientists to generate in the laboratory the circulating blood cells required for transfusions and transplants.
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Comment:Researchers success in isolating hematopoietic stem cells could aid bone marrow transplantation, gene therapy.
Publication:Transplant News
Geographic Code:1USA
Date:Oct 14, 1999
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