SYLVATICA BIOTECH INC — Department of Health and Human Services SBIR Phase I: NICHD

Description

PROJECT SUMMARY ABSTRACTThis program aims to develop a novel storage method for human ovarian tissue and whole ovarieswhich can also be applied to testicular tissue and gonadal preservation as well as a variety of cellstissuesand whole organsThis multi pronged approach builds on recent advances in machine perfusionnature inspired cytoprotection strategiesand non toxic cryoprotectant solutionscombining them with our novel method for constant volumepressure assisted coolingOur method promises to achieve vitrification of living tissues without the aid of toxic concentrations of cryoprotectantsin a system at thermodynamic equilibrium and potentially at temperatures as high asCIt ameliorates or entirely circumvents many of the limitations of conventional cryopreservation methods for large tissuesincluding damaging ice crystallizationeleterious changes in solute concentrationsand volumetric changesThis approach has the potential to enable indefinite banking of ovarian tissueswhole ovariesand other living materials while dramatically limiting tissue injury currently associated with ex vivo storageThe technical objective of this Phaseproposal is to develop an optimized cocktail and protocol for preservation and indefinite banking of ovarian tissue stripsWe will develop our method across three specific aimsIn Aimwill use well established methods developed in one of our labs for comprehensive thermodynamic characterization of novelnature inspired cryoprotectant solutions in an isochoricconstantvolumesystemthis will allow us to select solutions that allow for pressure assisted vitrification of living materials at low to intermediate pressures and much higher temperatures than traditionally needed for ice free cryopreservationIn Aimwe select the most effective cryoprotectant solutions established in Aimto optimize ourhigh sub zero vitrificationin a cell based model for ovarian tissue consisting of human primary ovarian epithelial cellshuman primary ovarian granulosa cellsand human endothelial cellsusing highthroughput combinatorial testingwe will select protocols which maximize cell viability and improve on current preservation standardsIn Aimwe will test our optimized protocols for the preservation of human ovarian cortical tissue stripsalong with one of the most successful protocols for ovarian tissue freezing and for ovarian tissue vitrificationrespectivelywe will additionally test the augmentation of these methods with subnormothermic machine perfusionenabling further reduction of ischemic tissue injurySuccess of these novel approaches individually or in combination will likely enable breakthroughs in clinical oncofertility and biopreservation PROJECT NARRATIVECancer treatment and research is inhibited by limitations in storage of biomaterials of every scalefrom whole ovariestestesand ovarian and testicular tissue to preserve the fertility of pediatric and young adult cancer patientsto the banking of patient biospecimens for researchit is no exaggeration that preservation breakthroughs can potentially save or change the lives of millions of cancer patientsWe have developed a novel approach to dramatically increase the effectiveness of ovarian tissue bankinghelping protect fertility and endocrine function in female cancer survivorsThis approach should be widely applicable for preservation of living systems