The differentiation potential of three existing kidney progenitor cell lines derived from rat and mouse metanephric mesenchyme (MM) and ureteric bud (UB) was examined during Phase I and found to undergo reciprocal induction to form a differentiated tubular epithelium and satellite (stromal) cells in 3-dimensional culture. Because, the kidney progenitor cell lines retain differentiation potential, they have enormous potential in state-of-the art research areas including stem cell biology, cell replacement therapy, tissue engineering, and other burgeoning fields in regenerative medicine. The basis of this Phase II application (in collaboration with the University of Texas Health Science Center at San Antonio and Southwest Foundation for Biomedical Research) is to procure embryonic kidney cells from rats and from baboons as a model for translational research to humans. The following aims are proposed:
Aim 1. To isolate and characterize additional progenitor cell lines derived from rat and baboon embryonic kidney. New embryonic MM, UB and nephrogenic progenitor (NP) cell lines derived from developing glomeruli and tubules in embryonic kidney will be isolated, characterized and included in the Probetex's cell bank for additional assay development and testing in experimental regenerative medicine.
Aim 2. To develop kits for the in vitro investigation of nephrogenesis. Kits will be developed to investigate different aspects of renal development by 1) Three- dimensional co-culture of various combinations of embryonic MM, UB, and NP cell lines and with and adult cells with diverse differentiation potential that may develop into specialized kidney structures. 2) Define the differentiation potential of embryonic cells in response to conditioned and defined medium for further characterization of the cell lines and as product for commercialization.
Aim 3. To define differentiation potential of kidney embryonic progenitor cells in cell replacement therapy for renal disease. Cell replacement therapy offers a novel and powerful medical technology. The therapeutic potential of embryonic kidney progenitor cells to selectively integrate, differentiate towards a renal fate, and repopulate damaged areas and accelerate the restoration of renal structure and function will be evaluated in rats and baboons. Two established experimental models of renal disease are selected, each for their selective damage specialized cell types. Ischemia/reperfusion targeting proximal tubular cells and bromoethylamine hydrobromide (BEA)- induced papillary injury targeting the loop of Henle and collecting ducts. Commercialization of these cells will provide an important resource for the study of renal development and regenerative medicine.
The potential impact of availability of renal stem cell technologies is enormous. Probetex's goal to create a Cell Bank of Embryonic Kidney cell lines will foster further research and development on kidney progenitor cells, enhancing our understanding of the basic science of growth and development of the kidney. Also, research in the stem cell biology will be instrumental in the procurement of new knowledge and methodologies for cell-based tissue and bioengineering approaches to renal disease.
| Patel, Mandakini; Velagapudi, Chakradhar; Burns, Hannah et al. (2018) Mouse Metanephric Mesenchymal Cell-Derived Angioblasts Undergo Vasculogenesis in Three-Dimensional Culture. Am J Pathol 188:768-784 |
| Velagapudi, Chakradhar; Nilsson, Rune-Par; Lee, Myung Ja et al. (2012) Reciprocal induction of simple organogenesis by mouse kidney progenitor cells in three-dimensional co-culture. Am J Pathol 180:819-30 |
