?Stroke is the leading cause of disability in adults in the Western world. Its socioeconomic impact is staggering. Most stroke patients currently have no treatment option given that the only FDA-approved stroke therapy, intravenous tPA for treatment of thrombolysis, must be administered within 5 hours of stroke onset and only about 5% of stroke patients present for treatment within that time window. The development of a therapy with a longer treatment window could benefit the other 95% of patients not currently served. Mesenchymal stem cell (MSC) therapies have shown promise in cerebrovascular disease models; however, their mechanism of action is predominantly through paracrine support of endogenous repair mechanisms rather than direct tissue replacement. We and others have demonstrated the therapeutic potential of cell-free conditioned medium derived from adult MSCs isolated from adipose tissues. Importantly, we have observed morphological and functional benefits when our therapy, NFx-101, is delivered up to 36 hours following onset of ischemia. We propose to demonstrate the efficacy of NFx-101, a partially purified adipose stem cell-derived conditioned medium, when delivered between 6 and 24 hours after ischemia in a clinically relevant, partially humanized mouse embolic stroke model. Mice will be evaluated for morphological and functional changes as a result of treatment. If successful, NFx-101 could become a breakthrough therapy for stroke victims.
Public Health Relevance Statement: Public Health Relevance: Stroke causes more disabilities in adults of industrialized countries than any other medical condition. Only 5% of the 700,000 annual stroke patients in the United States are eligible for treatment with the only approved drug that removes the blockage of blood flow causing stroke. We propose a therapy based upon beneficial factors produced by adult stem cells that could potentially benefit the other 95% of patients by reducing damage and restoring brain functions.
NIH Spending Category: Brain Disorders; Neurosciences; Regenerative Medicine; Stem Cell Research; Stem Cell Research - Nonembryonic - Non-Human; Stroke
Project Terms: Acute; Adipose tissue; Adolescent; Adult; adult stem cell; aged; Alteplase; Animals; base; behavior test; Biological; Blood flow; Bolus Infusion; Brain; Brain Injuries; Brain Ischemia; cell motility; Cell Therapy; Cells; cerebral atrophy; Cerebrovascular Disorders; clinically relevant; Collaborations; comparative efficacy; Conditioned Culture Media; Data; Developed Countries; Development; disability; Disease model; Dose; drug candidate; Drug Interactions; Effectiveness; Evaluation; Family suidae; FDA approved; Female; Fractionation; functional improvement; functional outcomes; Goals; Harvest; Health Care Costs; Hospitals; Hour; Human; Image; improved; In Vitro; in vivo; Incidence; Individual; Injection of therapeutic agent; Intravenous; Ischemia; ischemic lesion; Ischemic Stroke; Laboratories; Lead; Legal patent; Magnetic Resonance Imaging; male; Medical; Mesenchymal Stem Cells; Modeling; Mus; Natural regeneration; neurogenesis; novel; Operative Surgical Procedures; Outcome; paracrine; Patients; Penetration; Performance; Pharmaceutical Preparations; Phase; Population; Preparation; Process; Proteins; public health relevance; Qualifying; repaired; research clinical testing; Research Infrastructure; safety study; socioeconomics; stem cell therapy; Stem cells; stroke; stroke therapy; subventricular zone; System; Temperature; Testing; Therapeutic; thrombolysis; Time; Tissues; Toxic effect; United States; Validation; Western World; white matter; young adult
