Congenital diseases of the genitourinary tract (kidneys, bladder, ureter, urethra etc.) are a leading cause of organ failure carrying with it an increased risk of death, and are a growing public health burden. At present, the only therapies are dialysis (for the kidneys) and organ transplantation. With the demand for transplants far exceeding supply there is an imminent need for alternate therapies. A comprehensive understanding of how the genitourinary tract develops in utero is necessary to effectively develop novel therapies to replace or repair injured tissue. The GenitoUrinary Development Molecular Anatomy Project (GUDMAP) has been successful at providing a high-resolution map of gene expression in the mouse GenitoUrinary system. However, a similar description has not been available for the human genitourinary system, nor has it been possible to develop optimized experimental techniques to grow, expand and differentiate human genitourinary progenitor cells in vitro. These research efforts by the developmental biology community have been hampered by the lack of a central hub for the procurement, quality control and distribution of human genitourinary samples. The Health Sciences Tissue Bank (HSTB) at the University of Pittsburgh has been involved in human tissue procurement for over 18 years, with a long standing history of collecting, maintaining and disbursing quality samples to research scientists, both in house and outside the University of Pittsburgh. HSTB is embedded within the Department of Pathology of the University of Pittsburgh Health Systems; thus providing rapid access to very high quality tissue and biological specimens. HSTB has established consenting protocols in line with the best practices recommendations from the NIH, a strong informatics backbone to facilitate specimen procurement and annotation, and has in place a robust quality control and quality assurance programs. The HSTB biorepository is fully accredited by the College of American Pathologists (CAP). HSTB has an established program accruing fetal tissues. The fetal tissue IRB has been in place since 2005. HSTB has the infrastructure for dissecting specimens and collecting different tissue types. In this calendar year, we have disbursed over 300 fresh samples collected from 77 cases. The collections can be significantly ramped up as material could have been accrued from as many as 725 cases last year. We have preliminary data showing that we can isolate the human urogenital system (kidneys, ureters and bladders) from various developmental ages (6-24 weeks). We have produced publication quality images of these genitourinary organs (including kidneys and bladder) and have also been able to isolate and expand cells from various genitourinary organs. Further, we have shipped high quality tissue to various GUDMAP investigators and they have verified the quality of the tissue sent. We propose to act as both the GUDMAP Tissue Hub and Tissue Gathering site to build upon the pre-existing specialized collecting abilities of HSTB and provide high quality genitourinary samples to members of the scientific community including those within GUDMAP.
An understanding of human genitourinary development is critical to tackling the growing number of developmental diseases affecting these tissues. This grant proposes to leverage the significant infrastructure of the University of Pittsburgh to provide high quality fetal tissue to the GUDMAP atlas projects.