Ligand-Targeted Phage Particles as Tools for Progenitor Cell Tracking, Gene Delivery, and Biomarker Discovery
Human pluripotent stem cells offer the potential of a continually self-renewing source of human cells that can become any tissue or cell type needed to treat human degenerative diseases such as heart failure, diabetes, macular degeneration, MS, ALS, Alzheimer's, and Parkinson's as well as spinal chord injury and other wound healing. Until recently, human embryonic derived stem cells were the principal source of pluripotent cells. New techniques like reprogramming adult human cells point the way to more plentiful and cost-effective cells for research and development. However, our understanding of how to efficiently make specific cell types such as heart or skin cells on demand starting from pluripotent stem cells and how to produce sufficient clinical grade quantities of cells needed for therapy is currently quite limited and presents a significant challenge for researchers in the field of regenerative medicine. Our proposed research offers to directly address this issue by developing research tools and techniques for understanding and monitoring differentiation of human pluripotent stem cells. As pluripotent cells grow and change in a dish in the laboratory they progress to cells that are programmed to become various mature cells based on environment signals. We propose to create targeted bio-probes that will recognize and label only very specific populations of early precursor stem cells. The bio-probes will leave an indelible color coded mark on their target cells so that we can track the progression of these cells over time and determine what type of cells they become in response to interaction with other cells and other environmental cues. We will use time lapse photography to make movies showing color coded precursor cells as they grow, migrate, divide and change into functional mature body cells such as skin or beating heart cells. The ability to mark specific populations of progenitor cells will allow researchers to also isolate them to study their growth and development under various conditions aimed at producing desirable mature cell types from the progenitors. The new tools we propose to develop will help researchers distinguish one stem cell derivative from another so that well characterized cells can be prepared for disease therapies that are free of unwanted cell types.
About half of California's families have a child or adult who has suffered or will suffer from a serious medical conditions that could potentially be treated with stem cell therapies whether it be cell transplantation, the use of drugs tested on stem cell derived cells or drugs that affect endogenous stem cells to promote healing. The proposed research will result in new tools and technologies for identifying, isolating and tracking progenitor cells that are derived from pluripotent stem cells. Recent advances allow more ready access to pluripotent stem cells through reprogramming however there remains a critical need to understand how efficiently derive cells for therapy or drug testing. The innovative and versatile tools we propose to develop would allow California researchers to to tag lineage specific cells derived from any pluripotent stem cell line at any point in development. Multiple probes can be used to study two or more lineages at the same time. The technology can be used to target progenitor cells with a known biomarker interaction or to identify new surface markers or combinations that distinguish one type of precursor cell from another. These tools will make it easier for researchers to understand how to derive useful therapeutic cells from embryonic and other types of stem cells in the laboratory, to determine how to make and scale up pure cell populations that are free of unwanted cells and thus facilitate the translation of research to the development of cells and regenerative medicines for treating the patient population of California. An added benefit to California will be that the movies we create of differentiating ES cells will have important educational value for the general public's understanding of stem cells and their potential for curing disease. There are many other benefits to California researchers that will result from the development of the proposed progenitor targeting probe technology among them are improved assay development for differentiation agents, characterization of cells for transplant, and monitoring the fate of transplanted cells. Our proposed tools would therefore benefit the California economy by advancing the biomedical industry.