Development of a device for the identification and quantification of cancer stem cells
Regenerative medicine holds great promise for the treatment of a host of human diseases. The remarkable regenerative potential of stem cells puts them at the forefront in terms of options in regenerative medicine. The use of pluripotent stem cells to generate tissue (sometimes called adult) stem cells is one of the most promising strategies for success in development of novel cell-based therapies and diagnostics. However, the generation of tissue stem cells, from pluripotent stem cells, for potential applications must employ laboratory methods for cell generation, maintenance and expansion that increase the risk of generating cancer stem cells. For example, many pluripotent human embryonic stem cell (hESC) lines are known to be contaminated with cells that have undergone cancer-causing mutations. Furthermore, substantial numbers of mice reconstituted with islet cells derived from induced pluripotent cells (iPSCs) developed tumors. Thus, a critical bottle neck in bringing any pluripotent cell-based therapy to the clinic is overcoming our limited ability to identify malignant cells that contaminate cell cultures intended for regenerative medicine.
In addition to applications in regenerative medicine, another aspect of stem cell biology has immense potential for novel therapeutic applications. In order to develop a clearer understanding of breast cancer biology, our group has begun to apply the principles of stem cell biology to breast cancer in humans. Data generated from our laboratory has demonstrated that many common cancer tumors contain populations of tumorigenic, immortal, cancer stem cells (CSCs), as well as and non-tumorigenic cancer cells. Indeed, as few as 100 CSCs were able to form tumors when injected into immunodeficient mice and these resultant lesions contained the full, phenotypically-heterogeneous population of CSCs and non-tumorigenic cancer cells found in the patient’s original malignancy. Since our evidence suggested that stem cells drive tumor development, we hypothesized that resistance of the CSCs would contribute to relapse after cytoxic radiotherapy and chemotherapy. This prediction has now been borne out. Recently, using single cell analyses of stem cell pathways, we have developed a novel way that should make it possible to accurately identify and count cancer stem cells in both pluripotent stem cell cultures and biopsy specimens. This opens the door to a rapid and simple assay that could be used to quickly determine the risk and effectiveness of a treatment regimen for an individual patient.
This research has the potential to significantly benefit the State of California and its citizens. First, this research could solve a potentially serious complication for the use of stem cells in the clinic. For example, transplantation of insulin-producing cells has the potential to cure diabetes. However, there is a risk that the laboratory grown cells used for such treatments could become cancerous. If successful, our studies will reduce this risk and thus help to enable clinical trials to proceed with less risk of this serious complication. Next, this research should lead to a new diagnostic that can be used to optimize the therapy that a patient with cancer receives. This would reduce the side effects that a patient is exposed to and would increase the chances that a particular treatment will be effective. Finally, if these projects are successful, they will generate new instrumentation that must be commercialized. This will lead to more high-paying jobs for the State of California.