Microfluidic Platform for Stem Cell Applications

DESCRIPTION provided by applicant The emerging field of stem cell therapy has the potential to transform medicine forever However a major bottleneck for bringing stem cell therapies to the patient is the lack of adequate in vitro assays for the study of stem cell quality Critical test criteria are efficacy pluripotency prior to the differentiation process and safety lack of tumorigenicity after differentiation prior to implantation of stem cell derived tissues The simplest assay available to assess stem cell quality is the embryoid body EB assay However this assay is not able to support tissue growth long enough to achieve complete teratoma development Therefore the present gold standard for testing stem cell quality relies on in vivo testing by injecting stem cell preparations into immunodeficient mice This so called andquot teratoma assayandquot assesses the stem cellsandapos pluripotency the ability to develop into cell types derived from all three embryonic germ layers Unfortunately this in vivo assay has significant drawbacks it requires a large number of animals is prohibitively expensive time consuming labor intensive and results are dependent on surgical skills The proposed projectandapos s objective is to develop an in vitro assay based on a microfluidic chip containing a tissue engineered vascularized humanized microenvironment for testing stem cell pluripotency Preliminary data obtained with the Nortis technology suggest that the proposed in vitro model can perform the pluripotency test much more economically and in a much shorter time frame than the in vivo teratoma assay Additionally our data indicate that perfused microvasculature incorporated into stem cell environment is key to long term viability and differentiation of human teratoma tissue During Phase I we will develop the microfluidic hardware and tissue engineering protocols Specific Aim Additionally we plan to demonstrate feasibility that the assay can be performed with a quality and robustness that complies with the requirements for assessing stem cell pluripotency Specific Aim We will compare the performance of our teratoma chip directly with currently available methods the EB assay and in vivo teratoma assay Minimum feasibility requirements for Phase I are to meet the performance quality and run time of the in vivo assay at significantly reduced costs During Phase II we will dedicate major Randamp D to validate the assay and increase throughput capabilities Ultimately the proposed product will provide researchers in academia and industry with a powerful new in vitro tool that will fuel the development of groundbreaking stem cell therapies and their clinical translation PUBLIC HEALTH RELEVANCE The emerging field of stem cell therapy has an enormous potential to transform medicine forever but lacks predictive tests for evaluating the quality of stem cells to be used in clinic The proposed project aims to develop an in vitro assay for evaluating stem cell quality based on a microfluidic chip containing a tissue engineered microenvironment that supports stem cell growth and differentiation Successfully accomplished project will provide researchers in academia and industry with a new generation in vitro tool that facilitates the discovery and development of new stem cell therapies and their translation to clinic across a wide range of human diseases