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Research Finds Bone-Marrow-Derived Stem Cells Can Reverse Genetic Kidney Disease
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Research Finds Bone-Marrow-Derived Stem Cells Can Reverse Genetic Kidney Disease

Research Finds Bone-Marrow-Derived Stem Cells Can Reverse Genetic Kidney Disease
News

Research Finds Bone-Marrow-Derived Stem Cells Can Reverse Genetic Kidney Disease

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The discovery that bone-marrow derived stem cells can regenerate damaged renal cells in an animal model of Alport syndrome provides a potential strategy for managing this inherited kidney disease and offers the first example of how stem cells may be useful in repairing basement membrane matrix defects and restoring organ function.

Led by researchers at Beth Israel Deaconess Medical Center (BIDMC), the findings are described in the Proceedings of the National Academy of Sciences (PNAS), which appears on-line the week of April 24, 2006.

"This is one of 31 human diseases that occur because of genetic defects in the body's extracellular matrix and basement membrane proteins," explains the study's senior author Raghu Kalluri, PhD, chief of the division of matrix biology at BIDMC and associate professor of medicine at Harvard Medical School

Present throughout the body, the extracellular matrix (ECM) is made of collagens, proteogylcans, noncollagenous glycoproteins and in some tissues, elastin fibers.

The ECM serves a unique role by constructing a "scaffold" for cells, thereby maintaining the structural integrity of many tissues.

"In normal kidneys, a specialized form of extracellular matrix known as the glomerular basement membrane (GBM), composed primarily of type IV collagen, is the key component of the blood filtration apparatus," says Kalluri.

"With no known cure, treatment options for Alport syndrome are limited to kidney transplantation or lifelong dialysis," he adds.

"Our lab set out to determine if bone marrow-derived stem cell therapy might provide another treatment option."

Using a mouse model of the disease, in which COL4A3 - one of the three type IV collagen genes that is mutated in Alport patients - had been removed, the researchers transplanted allogenic bone marrow into the knockout mouse.

According to Kalluri, within a period of about four weeks, the investigators found that approximately 10 percent of the transplanted cells had incorporated into the damaged regions of the kidney glomeruli in the knockout mouse, emerging as healthy renal cells (podocytes and mesangial cells).

This led to clear improvement in the animal's kidney function and repair of the glomerular architecture defects.

"These results offer a possible therapeutic opportunity for both children and adults with Alport syndrome," he says.

In addition, the findings demonstrate that bone-marrow-derived stem cells can be used to repair extracellular/basement membrane defects, and according to Kalluri, the researchers' next step will be to see if the use of embryonic stem cells and circulating adult stem cells will achieve the same function.

"This new evidence offers hope that this is a treatment strategy that can be explored for other diseases that result from extracellular matrix defects," he notes.

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