"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 new 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.
Study coauthors include BIDMC researchers Hikaru Sugimoto, MD, PhD, Thomas Mundel, MD, PhD, Malin Sund, MD, PhD, and Liang Xie, PhD, and Dominic Cosgrove of Boystown National Research Hospital, Omaha, Nebraska.