Urine-derived Stem Cells For The Treatment Of Chronic Kidney Disease In A Rat Model

Background:Chronic kidney disease is a common disease that may lead to uremia and cardiovascularcomplications, and its incidence rate has been on the rise. Approximately13%of the worldpopulation are suffering from chronic kidney disease, making it a major health care problem.In our country, the incidence rate of chronic kidney disease is also high, affecting10.25%ofthe population. Chronic kidney disease is progressive. It may finally become end-stage renaldisease, which will bring about huge economic burden. In2007alone, the expenditure ofUnited States on end-stage renal disease was almost23billion US dollars, accounting for5.8%of total Medicare budget. Current treatments against end-stage renal disease are limited.Dialysis and renal transplantation are the most effective methods. However, dialysis is a longprocedure with many complications that will decrease patients’ quality of life. Moreover, itonly replaces kidney’s filtration function and cannot replace the endocrinal function and so on.On the other hand, the biggest obstacle of renal transplantation is the shortage of donor organs.Furthermore, the problem of tissue rejection and the consequences of immune suppresscannot be easily solved. Therefore, new therapies are needed.Cell therapy has been attracting growing interests. Stem cells, because of their abilities toself-renew and differentiate into different kinds of cells, have made promising progress inalmost every research field. Urine-derived stem cells are a new source of stem cells. Theybelong to the mesenchymal stem cell family, and can be derived non-invasively from freshurine. Mesenchymal stem cells may be beneficial for renal functions. Because urine-derivedstem cells may come from kidneys, it may be a better cell source to treat chronic kidneydisease.Purpose:To study whether urine-derived stem cells can treat chronic kidney disease and to brieflydiscuss the mechanisms.Methods:1. Urine-derived stem cells were harvested from health donors. Cells werecharacterized through the abilities of self-renew and multipotent differentiation, aswell as the expression of surface markers. 2. Urine-derived stem cells were injected into the kidneys of athymic mice. The micewere sacrificed at1-week,2-week,3-week, and4-week time points. The kidneyswere harvested, and urine-derived stem cells were located by antibodies. Surfacemarkers were tested to see the possibility of renal differentiation.3. Athymic rats were divided into3groups: age-matched control group, chronic kidneydisease models injected with urine-derived stem cells, and chronic kidney diseasemodels injected with phosphate buffered saline. Renal function, including serumcreatinine and glomerulus filtration rate, of the3groups were followed. Thehistological evaluation of the kidneys of the3groups were also performed.Results:1. Urine-derived cell clones were able to self-renew, and differentiate into osteocytesand adipocytes. These cells express mesenchymal stem cells markers such as CD24,CD29, CD44, CD73, CD90, CD105, CD146, and so on. On the other hand, they donot express hematopoietic markers such as CD31, CD34, and CD45.2. Urine-derived stem cells survived inside the kidney. Within the limited time offollow-up, no cell fusion was observed under microscope. Urine-derived stem cellsstill expressed mesenchymal stem cells markers meaning that they may notdifferentiate into renal cells.3. Urine-derived stem cells may improve renal functions. Compared with modelsinjected with phosphate buffered saline, models injected with urine-derived stemcells had lower serum creatinine levels and higher glomerulus filtration rates.Urine-derived stem cells may improve the structure of kidney as well. Comparedwith models injected with phosphate buffered saline, models injected withurine-derived stem cells had more healthy nephrons, decreased type I and type IIIcollagen, and less inflammatory filtration.Conclusions:Urine-derived stem cells may an alternative treatment method for chronic kidney disease.These cells can be derived from fresh urine and may be a non-invasive, autologous cell sourceto treat chronic kidney disease. The mechanisms needs further studying, and modifiedtreatment plans are needed.