SBIR-STTR Award

BioLife Technologies is a wholly owned subsidiary of Cryomedical Sciences (CMS) incorporated on March 31, 1998 under the General Corporation Law of the State of Delaware. BioLife's primary mission is to develop improved hypothermic (cold storage) solutions designed to maintain cells, tissues and organs in a near state of suspended animation at 4 degrees C. Cardioplegia, organ transplant and selected non-regulated markets have been targeted. Data presented herein demonstrate that BioLife's hypothermic solutions, the HypoThermosol (HTS) series, are better at cold-protecting kidney, heart and skin cells than is ViaSpan - a product produced by DuPont-Merck. ViaSpan currently commands the largest market share in the transplant solution business, but it has not been significantly modified since its introduction 10 years ago. More importantly, the design of ViaSpan is not based on modern molecular biology investigations. BioLife has launched an aggressive program to determine the molecular basis of cell death during extended hypothermic storage so that knowledge of these events can lead to a new generation of hypothermic solutions. DNA gels presented in this proposal demonstrate that cells cold stored for too long die by apoptosis (programmed cell death) two days after they are returned to normothermic (37 degrees C) temperatures. HTS supplemented with apoptosis inhibitors blocks this process and improves HTS's performance. CMS patent lawyers have advised BioLife Technologies that the inclusion of apoptosis inhibitors in a future generation series of FITS solutions warrants a patent application. The Specific Aims of this Phase I project are to determine if: (1) apoptosis that occurs during extreme hypothermia is best prevented when apoptosis inhibitors are added before, during and/or after the hypothermic event; (2) if hypothermia-induced apoptosis occurs to human skin, kidney, liver, lung and aortic cells; (3) activation of cell death inhibiting genes prevents hypothermia-induced apoptosis; (4) inhibition of apoptosis thought to occur during cryopreservation (-180 degrees C) also increases the efficacy of HTS cryopreservative solutions. Successful completion of this Phase I SBIR will lead to (1) improved cold storage solutions based on sound molecular biology investigations and (2) a patent protection package that will preclude any other company from developing similar cold storage solutions based on apoptosis inhibition. PROPOSED COMMERCIAL APPLICATIONS: BioLife Technologies proposes to develop solutions to be used for the hypothermic storage of cells, tissues and organs. Applications may include engineered tissues, cardioplegia and organ transport/transplant.

Thesaurus Terms:
cryopreservation, programmed cell death, protease inhibitor, technology /technique development, tissue /organ preservation BCL2 gene /protein, inhibitor /antagonist

BioLife Solutions Inc. was incorporated in March, 1998, and specializes in developing solutions and procedures for the hypothermic and cryopreservation of human cells, tissues and organs. The Company's research staff is composed, in part, of molecular biologists who have accumulated evidence supportive of the concept that the best manner in which to formulate future preservation solutions is to understand the molecular cell death cascades that are triggered during preservation storage regimes. BioLife has developed the HypolhermosolR (HTS) family of hypothermic and cryopreservative solutions that is designed based on this molecular biology strategy and is uniquely formulated for cell-specific applications. BioLife's successful completion of the Phase I work described herein has resulted in the sale of HTS to several corporate, academic, and government groups. BioLife has selected to work with Vitagen Corporation and the University of Miami Diabetes Research Institute (DRI) to develop two special HTS formulations for the shipping/storing of Vitagen's Extracorporeal Liver Assist Device (HTS-ELAD) and DRI's transplantable pancreatic islets (HTS-ISLETS). BioLife proposes three research themes in this Phase II SBIR. First, BioLife will continue its basic research on the molecular mechanisms underlying preservation-induced cell death. This basic research initiative is unique in the preservation industry and contributed to DRI's adoption of HTS for human islet transplantation. Second, BioLife will modify HTS with apoptotic and necrotic inhibitors identified through the literature as well as Vitamin E analogues synthesized through combinatorial chemistry so that HTS-ELAD and HTS-ISLETS can be optimized. Finally, the most challenging theme of the Phase II project is to develop a ProteinChip microarray high throughput assay system that will be the keystone of BioLife's Phase III additive discovery program. This, in turn, will allow the company to perform rapid assays by harnessing the microarrav technology so that additional I-ITS variants can be developed for future clients.

Thesaurus Terms:
apoptosis, cell death, cryopreservation, technology /technique development, tissue /organ preservation BCL2 gene /protein, antimetabolite, cell sorting, cysteine endopeptidase, enzyme activity, high throughput technology, microarray technology, pancreatic islet, protease inhibitor, proteomics, solution, tocopherol biotechnology