Chemically produced neural progenitors loaded with ferumoxide-protamine sulfate complex for visualization of gliomas

Glioblastoma is a highly invasive tumor with a recurrence rate ofwhich is in most cases rapidly fatalThe failure of current clinical and experimental therapies to eradicate disseminated glioma cells results in tumor recurrence and a median survival ofmonthsFurthermorecurrently available imaging technologies are not sufficiently sensitive for detection of small tumor satelliteswhich are responsible for recurrenceRecent research advances have established mesenchymal stem cellsMSCsneural stem cellsNSCsand neural progenitor cellsNPCsas promising therapeutic delivery vehicles for gliomasThese stem cells track down cancer cells in the tumor mass as well as migratory cancer cells into the brain parenchymaBecause of this unique abilitythe use of MSCs and NSCs NPCs as therapeutic and imaging modalities has been exploredSeveral recent studies demonstrated many advantages of NSCs over MSCsSpecificallyNSCs have a unique ability to suppress tumor growth in vivoand exhibit greater and more specific tropism to gliomasThe disadvantage of NSCs is the lack of an adequate NSC sourceCurrent alternative approaches to produce NSCs by induced pluripotent stem celliPSCtechnologies are fraught with incalculable risksRecentlywe have been able to generate neural stem progenitor cells from human bone marrow and adipose derived MSCs using a purely chemical approachor small molecule approachthat has several advantages over currently known technologiesOur recent studies demonstrated that these chemically induced neural progenitorsCiNPCsexhibited higher migratory capacity to malignant glioma DGM cells compared to hMSCs which was further increased by pre exposure of these cells to DMG conditioned mediumGCMThusCiNPCs produced by our recently developed safefastreproducibleand cost effective reprogramming approach can be efficiently used as a drug delivery vehicle for the treatment of brain tumors and or as carriers for magnetic resonance imagingMRIcontrast agents for visualization of gliomasThe goal of this SBIR phase I proposal is to investigate whether GCM pre exposed and magnetically labeled CiNPCs could be utilized for visualization of intracranial DMG glioma cells by MRIPhase II studies will investigate the potential use of these cells for MRI visualization of different types of gliomasCommercial and clinically compatible research products emerging from Phase I II work includes technology for large scale clinical grade production of magnetically loaded CiNPCs that can be used for visualization of different gliomas by MRITo achieve these goals the following Specific Aims are proposed for Phase I studiesSpecific Aimwill test the hypothesis that GCM preexposed CiNPCs loaded with ferumoxide protamine sulfate complexFE Prowill retain their viability and tropism to DMG cells in vitroSpecific Aimwill test the hypothesis that GCM pre exposed and FE Proloaded CiNPCs will exhibit tropism to DMG glioma xenografts in vivowhich can be monitored by MRI Since stem cells have a tendency to track down cancer cells in the tumor mass as well as those that have migrated away from the bulk of the tumor into the brain parenchymastudies have explored the use of stem cells as an imaging modality to determine the extent of tumor infiltration and to determine where the therapeutic stem cells are positionedRecentlywe have been able to produce neural progenitor cells from human adult mesenchymal stem cellsMSCsby safeefficient and cost effective method and demonstrated their specific high migratory capacity to gliomas in vitroThe goal of this SBIR proposal is to investigate whether these chemically induced neural progenitors could be utilized as carriers for MRI contrast agentsmagnetic particlesfor visualization of gliomas