The future success of regenerative medicine depends on our understanding of human stem cell biology. Stem cells are unique because they have the capacity to generate many different cell types. The goal of regenerative medicine is to harness the power of stem cells to repair or replace damaged tissue due to disease, aging, trauma or inherited defects by generating new, functional and transplantable human tissue in the laboratory. To accomplish this, it is imperative to define how tissue specific stem cells (also termed adult stem cells), cells capable of generating each cell type within a specific organ (i.e. blood stem cells generate both red blood cells and white blood cells), develop from conception to adulthood. However, inadequate tools and resources to identify, isolate and purify tissue specific stem cells are major roadblocks in tracking and profiling tissue specific stem cells throughout development. This issue confounds the development of novel therapeutics from pluripotent stem cells, which posses the potential to become any cell in the body, including tissue specific stem cells. We have developed a new systematic approach to isolate and study rare tissue specific stem cell populations. The focus of this project is on two adult stem cell populations, hematopoietic (blood) and hepatic (liver). Our approach includes isolating hematopoietic and hepatic stem cells from human fetal and adult tissues using known cell surface markers, followed by molecular profiling studies to identify new markers that will further enrich for the stem cell population. Monoclonal antibodies (molecules designed to target specific cell surface markers) will be generated to bind and tag the newly identified markers. These antibodies will aid in separating stem cells from other cells. Every novel marker identified will be functionally validated to ensure that real stem cells are isolated. This process is repeated continuously to further enrich for a pure stem cell population. Our findings will not only provide the field with standardized methods and tools to define novel markers for human adult stem cell identification, isolation and purification but will also directly advance efforts in regenerative medicine specifically targeted for blood and liver disorders by providing new reagents for the identification of hematopoietic and hepatic stem cells.
In an era of healthcare reform and economic depression, the growth of the State of California largely depends on the innovation and discovery generated by both its academic and industrial sectors. This project represents a collaboration between academia and industry to advance the translation of stem cell research from bench to bedside. A major roadblock in accomplishing this goal is our limited understanding of the biology of human tissue specific stem cells due to a lack of resources and necessary reagents. Tissue specific stem cells are unique cells capable of regenerating an entire organ. The studies proposed herein will provide the stem cell community with new tools,reagents and standardized methods to identify, isolate, purify, characterize and molecularly interrogate human tissue specific stem cells to advance the development of stem cell-based therapeutics. These new therapies will impact on children and adults suffering from diseases of the blood and liver. The data produced has the potential to directly impact California citizens and their families who have a disease or disorder that could benefit from stem cell therapy.