Oncogenicity and function of mosaically aneuploid human stem cells
A major challenge in all human therapies, as paraphrased from Hippocrates, is “to do no harm” in treating patients. This proposal is designed to reduce or eliminate possible harms of stem cell therapies by improving their safety as well as effectiveness through the exploration of a new phenomenon observed in stem cell populations called “mosaic aneuploidy.” Mosaic refers to an assembly of similar yet distinct things, while aneuploidy refers to deviations from the normal number of chromosomes that should be present in a cell. Thus, a population of cells with different chromosomal compositions represents mosaic aneuploidy. We have found that stem cell populations in fact contain many different forms of aneuploidy. The repercussions of this mosaic aneuploidy are not known. Alterations in chromosome number have well-documented liabilities, as observed in Down Syndrome (where patients have 3 copies of chromosome 21 rather than the normal 2 copies), and many cancers where multiple chromosome copies are present. However, some forms of aneuploidy may in fact be advantageous. This proposal will determine functions for mosaic aneuploidies, and could lead to ways of eliminating “bad” stem cells while enriching for “good” ones, towards optimizing stem cell therapies in humans.
Health-related issues are major economic and societal challenges in the State of California. Stem cell science could provide new ways of treating major diseases that impact the state as well as its citizens, both directly through individuals, and indirectly through family members and friends. In addition to the development of new disease treatments, the infrastructure to develop this segment of the healthcare industry will benefit from studies supported by CIRM, towards bettering California and its citizens.