Expansion of "youthful" mesenchymal stem cells from elderly individuals for autologous cell-based therapies

SummaryAbstractOur group has recently licensed a technology enabling the identificationisolationand subsequent expansion ofyouthfulmesenchymal stem cellsMSCsfrom elderly individualsThis population is characterized by small size and expression of stage specific embryonic antigenSSEAPrior work indicates that smallSSEAsmallMSCsfunction in a manner similar to that of MSCs from young individualsMoreoverstudies suggest that while elderly MSCs contain a significant fraction of senescent cells expressing the senescence associated secretory phenotypeSASPsmallMSCs possess a secretory phenotype much more similar to young MSCsAs increasing evidence suggests that paracrine effects may be the most potent therapeutic mechanism of stem cellsand it is widely accepted that young stem cells are antiinflammatory and immunomodulatoryit is reasonable to suggest that smallMSCs may be effective in the treatment of various chronic inflammatory diseasesThe proposed studies test the feasibility of reducing an inflammatory reaction using smallMSCs isolated from elderly donors and expanded on a commercially available extracellular matrix that mimics the in vivo nicheCELLvoMatrixFeasibility will be determined in vitro using a lymphocyte proliferation assayand a microarray to characterize the cytokine profile of smallMSCs relative to young or elderly MSCsIt is expected that smallMSCs will possess an anti inflammatory cytokine profileand will inhibit activated T cells in the lymphocyte proliferation assayIf the results match expectationssmallMSCs may be used to address chronic inflammation in an animal model in a phase II studyAs inflammation is key to the pathogenesis of most age related diseasesthis approach has the potential to slow or reverse the progression of any number of degenerative diseases for which no adequate treatments currently exist NarrativeThe age associated decline in quality and quantity of adult stem cells severely limits the potential efficacy of regenerative medicine approaches to the treatment of degenerative diseaseAn effective strategy for obtaining large quantities of high quality stem cells from elderly individuals for autologous therapies has the potential to improve treatment outcomes for a wide array of disease conditions that are becoming more prevalent as the global population continues to ageTo achieve this goalwe propose to test the feasibility of utilizingyouthfulmesenchymal stem cellsobtained from elderly donors using a novel approachto treat inflammationa common factor in the pathogenesis of most age related diseases