Early Translational II
ICOC Funds Committed:
A great deal of attention has recently been focused in the area of stem cells as a possible alternative for the treatment of a variety of diseases. End stage renal disease (ESRD) has reached epidemic proportions in the United States. An estimated 400,00 US residents are in treatment for ESRD and just last year more than 60,000 individuals were awaiting a kidney transplant. Currently, dialysis or kidney transplantation remain the only viable treatments despite significant limitations to both. This situation along with an increasing shortage of donor organs has heightened interest in developing novel therapeutic modalities, especially in the area of chronic kidney disease. Alport Disease is a hereditary glomerulonephritis estimated to affect at least 1 in 20,000 people. It is a chronic kidney disease caused by genetic defects in one of the proteins (type IV collagen) that make up the Glomerular Basement Membrane (GBM), an important component of the kidney’s blood filter. Eventually the kidney is replaced by fibrosis or “scar” which leads to failure of the organ. Herein we focus on the application of a novel source of stem cells from amniotic fluid (AFSC). We have successfully demonstrated that these cells have the potential to differentiate into multiple cell types and when injected into experimental animals they can restore the functionality of multiple organs such us the kidney, lung, and pancreas. In particular, when injected in an animal model of Alport Disease, AFSC have the propensity to lessen inflammation and fibrosis, and restore renal function. Major advantages of AFSC are that they can be easily retrieved through amniocentesis with no injury to the embryo and that they do not form tumors (teratomas) in vivo. We hypothesize that AFSC could represent a readily available source of ethically acceptable, biologically unmodified stem cells that may prove useful as a novel alternative in stem cell therapy for a wide variety of chronic kidney diseases.
Statement of Benefit to California:
The State of California is home to some of the nation's best organ transplant and treatment centers. Having our laboratory next to one of California's busiest pediatric renal transplant programs, at Children’s Hospital Los Angeles, we have been aware of the growing shortage of organs for our patients and the need for good alternative therapies in the field of regenerative medicine. In particular we focused our attention on chronic kidney disease. The need for donor organs continues to rise every year and emerging technologies such as those offered by stem cell research may assist our patients as well as the adult citizens of California with alternative technologies that perhaps can make a significant impact in this field. A novel population of pluripotent stem cells exists within amniotic fluid, which can be easily obtained, stored, and possibly used for future regenerative medicine or clinical purposes without some of the same concerns over clinical compatibility as embryonic stem cells. We intend to characterize the potential of these cells in the treatment of chronic kidney disease for their possible use one day in the clinic. CIRM funding will ensure a competitive advantage for California in this innovative direction.