Design verification and enhanced risk mitigation tests for cytocompatibility evaluation of cell delivery devices

The purpose of this study was to evaluate the cytocompatibility of various cell delivery devices using a battery of tests under exaggerated conditions. These tests were carried out using a human embryonic cell line transfected with Toll-like receptors (TLR) and a human monocytic cell line. The TLR-transfected cell line was used to evaluate the potential for cell surface receptor modulation and consequent changes in downstream signaling pathways that could occur when passing cells through a device. TLRs are well characterized and respond to a range of relevant ligands; for these reasons, TLRs were used as representative receptors to indicate modulation of cell surface receptors. The human monocytic cell line was used to characterize the viability and metabolic activity of cells following incubation with media exposed to the test article for a set time. This assay evaluated the potential toxicity of substances that might be released from the medical device on the cellular product being delivered. Human monocytes were selected for use because they are well-characterized in the literature and familiar to academic and industrial labs. For each assay, all devices were incubated with complete cell culture media for a period of time far exceeding that expected for clinical use. Assays were performed after a set exposure period to the delivery device exposed media. Taken together, data generated from these tests may be representative of alterations that could arise in therapeutic cells when processed through medical devices and provide a basis for cytocompatibility evaluation of delivery devices.