High-throughput label-free screening of stem cell differentiation
A critical bottleneck in realizing stem cell-based therapies is the significant risk of tumor formation following treatment. Approaches used to direct pluripotent stem cells to medical-grade cells for these therapies may result in residual cells likely to form tumors once transplanted. Therefore, it is important to be able to recognize these residual unsafe cells or be able to predict if a batch of pluripotent stem cells is likely to yield many of these cells. Current approaches to identify these unsafe pluripotent cells have been developed for the research environment and are too costly and difficult to perform routinely. This has severely limited the practical realization of stem cell therapies. We have developed an automated and miniaturized approach to identify these unsafe cells based solely on their deformability (or ability to change shape when stretched) that promises to have significantly reduced costs. We propose to increase the accuracy of this approach through microfluidic and high-speed imaging technology development, and directly validate the approach for predicting tumor formation. Once guidelines have been developed for predicting tumor-forming potential we will implement this system to screen stem cell lines and their derivatives that are being developed for therapeutic purposes. This tool also promises to speed up the development of stem cell therapies by allowing high speed evaluation of many formulations that can be used to direct stem cell behavior.
We propose to develop an instrument to determine the tumorigenic potential and improve the safety of stem cell therapies. We expect that this instrument will benefit Californians by (i) enabling stem cell therapies to enter the clinic by addressing safety concerns, (ii) reduce the cost of these therapies and the economic burden on our healthcare system, and (iii) provide jobs when the technology is commercialized through a California-based startup or industry partner. A major bottleneck in achieving stem cell therapies derived from embryonic stem cells or induced pluripotent stems cells is the significant risk of tumor formation if undifferentiated cells are carried through with a cell-based treatment. By providing a cost-effective solution to identify these cells prior to implantation we hope to increase the safety of these treatments and thus the likelihood that they will be made available to Californians with devastating, currently incurable diseases. Besides improving the chances that these treatments will be available, our approach would reduce the cost of these therapies when compared to currently used approaches to identify and sort unsafe cells. Cost may play a large role in whether insurance companies will reimburse for these therapies. A reduced cost will also reduce the tax-payer burden for providing these treatments through public healthcare. In addition to reducing the tax-payer burden in providing care that includes stem cell-based treatments, the development of our instrument will create many well-paying high technology jobs located in California as it is commercialized. Product development based on our instrument will provide high technology jobs in instrument engineering, product design, software development, and business development for commercialization through a startup or local industry partner. If successful these instruments will be used across the nation and world leading to a hundred million dollar market that will stimulate California's economy.