SBIR-STTR Award

BioLife Solutions Inc. is a Biological Packaging Company dedicated to developing improved solutions for hypothermic (4 to 8C) and cryopreservation (-196C) of human cells and tissues. The Company generates revenues from direct sales of its two platform solutions, HypoThermosol (HTS) and CryoStor as well as executing Custom Solution Optimization Program contracts with cell therapy and tissue engineering companies. The HTS platform consists of HTS-BASE (the original HTS formulation); HTS-DCC (a formulation that controls cation flux); HTS-FRS (a formulation that controls free radical accumulation) and HTS-LIVER (a formulation that controls apoptosis in hepatocytes). The first three HTS formulations are available through MediaTech Inc, whereas the fourth is currently under development. CryoStor is an HTS solution designed for improved cryopreservation necessitating reduced amounts of cryoprotective agent (e.g. DMSO). BioLife has also launched a program in Packaging and Downloadable Diagnostics that will allow cell therapy/tissue engineering companies who currently use HTS to track the history of temperature, shock, and pressure changes that occur during cell product transit. BioLife's HTS platform solutions were designed originally to protect substrate-attachment cells. But the recent clinical success of HTS-FRS preservation of suspended human myoblasts used in BioHeart Inc's successful European cellular cardiomyoplasty trials, coupled with CryoStor's apparent superiority in cryopreserving ATCC human hybridomas, experiments recently performed by ATCC personnel, has demanded that BioLife launch a new research program to understand the stress mechanisms that occur to suspended cells prior to preservation. Four Specific Aims are proposed as follows: SAI: Improving preservation by occupying integrin receptors that, in turn, could block anoikis; SA2: Improving preservation through inhibiting cell shape change that occurs due to the suspension process; SA3: Improving preservation by blocking FAS activation, a known death receptor that the Company has linked to preservation efficacy; SA4: Test the dual-function free radical inhibitor, Emblica, to determine if a combination free radical/metal chelator can improve the preservation of suspended cells. The intent of this Phase I SBIR project is to better understand the stress mechanisms that need to be controlled for improved preservation of suspended cells that will lead to the Phase II development of HTS-SUSP.

Thesaurus Terms:
method development, preservation, stress, suspension, tissue /cell culture apoptosis, cell morphology, chelating agent, cryopreservation, cytoskeleton, extracellular matrix protein, free radical, integrin, receptor expression western blotting

Cell Preservation Services, Inc. (CPSI) is dedicated to the development of novel processes and devices in the area of biotechnology and medicine. CPSI research strategy focuses on understanding and manipulating the cell survival and cell death pathways activated in response to various stressors. Recently, we have recognized that it is not adequate to merely address stress response issues during isolated events of cell processing, as has been the focus in the past, but in fact a more comprehensive and strategy involving process integration and cellular conditioning is necessary. CPSI intends to apply this novel strategic approach to develop new methodologies to improve the quality (integrity and function) of human lung cells (hLC) and tissues beyond those typically realized today. Investigations conducted under this research project will utilize cDNA microarrays, proteomic profiling, and viability and functional analysis to define the stress response pathways activated in hLC during common pre-transplant manipulation and processing. It is the intent of these studies to provide a better understanding of the unique responses of hLC to ex vivo manipulation and utilize these data to develop new methodologies for cell processing. These developments should have an impact not only on the quality and availability of lung tissue samples, but also enable expanded utilization in areas such as in vitro study as well cell and tissue transplants.