A microfluidic quality-control assay for stem-cell derived therapies

Period of Performance: 03/21/2016 - 02/28/2017


Phase 1 STTR

Recipient Firm

Nortis, Inc.
Woodinville, WA 98072
Principal Investigator


? 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 teratoma assay assesses the stem cells' 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 project'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 1). 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 2). 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 R&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.