Precursors isolated from human embryonic stem cell culture: potential use for kidney regeneration

Funding Type: 
SEED Grant
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

End stage renal disease has reached epidemic proportions in the United States. In the U.S., more than 400,000 people are on chronic dialysis every year and another 20,000 patients have undergone a kidney transplant. Currently dialysis and transplantation remain the only viable treatment despite significant complications with both. This along with an increasing shortage of organs has heightened interest in developing novel methods of therapy for kidney replacement. A great deal of attention has recently been focused on stem cell technology as an alternative modality for the treatment of a variety of diseases. This is particularly true in the fields of tissue engineering and regenerative medicine, because stem cells have the capacity to differentiate into a variety of cell types and represent a potentially in-exhaustible source of cells that can be used to regenerate new tissue for transplantation.
A great deal of effort is focused in our laboratory to researching novel sources for stem cell lines. We have demonstrated that in culture, a new population of stem cells derived from human amniotic fluid exhibit the capacity to differentiate into normal organ structures in developing embryonic kidneys. These results encouraged us to pursue live animal models which have demonstrated similar outcomes after the induction of injury to the kidney. This is an important concept because this may represent a novel method for cell therapy in those patients with End Stage Renal Disease where recovery of the organ could be made possible.
In our efforts of continuing to examine other stem cell lines we would like to isolate another novel population of stem cells derived from human embryonic stem cell cultures and apply these cells to regenerative applications in the laboratory to determine their potential value in tissue regeneration. At the edge of human embryonic stem cell colonies, there exists a heterogeneous population of cells both differentiated and partially differentiated. These cells do not have the same pluripotential capacity as the undifferentiated stem cells near the center of the colony but also do not form teratomas (tumors), which affords them greater advantage for future clinical applications. We plan to isolate these precursors cells, establish their optimal culture conditions and characterize them. In addition we would like to show that these cells can differentiate into kidney cells and confirm that they do not form teratomas in live animals. The isolation of these precursor cells from human embryonic cultures may prove helpful in understanding some of the mechanisms of development and cell differentiation. However, most important characteristic of these novel precursor cells is that they may have viable future clinical applications, since they can be derived in virtually an unlimited amount and likely avoid the risk of tumor formation when applied into biological systems.

Statement of Benefit to California: 

The State of California is home of some of the nation's best organ transplant centers. Having our laboratory next to one of California's busiest pediatric renal transplant programs in the country, at Childrens Hospital Los Angeles, we became acutely aware of the growing shortage of organs for our patients. While the need for donor organs continues to rise every year, emerging technologies such as those offered by stem cell research may assist our patients and the rest of the citizens in California with alternative technologies that perhaps can make a significant impact in regenerative medicine and transplantation therapies. Although human embryonic stem cells show the capacity for multiple differentiation and the prospect for new medical cures, they also have an inherent propensity to form teratomas ( benign tumors) in culture which may actually limit their use for future clinical applications. However, a very novel population of precursor cells exist on the periphery of a typical human embryonic stem cell colony that maintain the ability for multiple cell line differentiation but will not form teratomas. These cells could possibly be a safer alternative for regenerative applications aimed at evolving into human clinical therapies that would help those citizens of California in need of organ replacement therapies in the future. We intend to characterize the potential these cells have for differentiation into various cell lines and test their capacity to differentiate into renal cells in the laboratory, a process by which we have extensive experience and success in performing with other precursor cells.