title: The significance of the host inflammatory response on the therapeutic efficacy of cell therapies utilising human adult stem cells.
abstract: Controlling the fate of implanted hMSCs is one of the major drawbacks to be overcome to realize tissue engineering strategies. In particular, the effect of the inflammatory environment on hMSCs behaviour is poorly understood. Studying and mimicking the inflammatory process in vitro is a very complex and challenging task that involves multiple variables. This research addressed the questions using in vitro co-cultures of primary derived hMSCs together with human peripheral blood mononucleated cells (PBMCs); the latter are key agents in the inflammatory process. This work explored the in vitro phenotypic changes of hMSCs in co-culture direct contact with monocytes and lymphocytes isolated from blood using both basal and osteogenic medium. Our findings indicated that hMSCs maintained their undifferentiated phenotype and pluripotency despite the contact with PBMCs. Moreover, hMSCs demonstrated increased proliferation and were able to differentiate specifically down the osteogenic lineage pathway. Providing significant crucial evidence to support the hypothesis that inflammation and host defence mechanisms could be utilised rather than avoided and combated to provide for the successful therapeutic application of stem cell therapies.
authors.affiliation: UKCTE, The Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L69 3GA, UK. mnavarro@ibecbarcelona.eu
authors.forename: Melba
authors.initials: M
authors.lastname: Navarro
authors.forename: Fanrong
authors.initials: F
authors.lastname: Pu
authors.forename: John A
authors.initials: JA
authors.lastname: Hunt
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000276:immunology / Q000502:physiology / Q000637:transplantation*; D064987:Cell- and Tissue-Based Therapy / Q000009:adverse effects / Q000379:methods; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006789:Host vs Graft Reaction / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D016207:Cytokines