IBA Publikation

Extern

Abstract:
AbstractRegeneration, tissue remodeling and organ repair after injury which rely on theregulated activity of tissue-borne stem cells become increasingly compromised withadvancing age.Mesenchymal stroma cells were isolated from bone of differently aged healthydonors. The rare population of mesenchymal stem cells (MSC) contained in theprimary cell isolates, barely declined in number, yet relative to the donor age thestem cells displayed diminished long-term proliferation potential. The expression ofvascular cell adhesion molecule 1 (CD106) was elevated on primary MSC. InCD106bright MSC, the abundance of a panel of stemness transcription factorsremained unchanged. As the CD106 level could be further enhanced by proinflammatorycytokines, we considered the rate of VCAM1 expression a goodreflection of an endogenous inflammatory milieu MSC are exposed to. Treatment ofMSC with increasing doses of interferon gamma exerted no immediate influence ontheir self-renewal capacity. It however impacted on the differentiation potentialtowards the adipogenic or osteogenic lineage. Moderately elevated levels ofinflammatory stimuli supported osteoblastogenesis while the same treatmentreduced adipogenic differentiation in MSC from young and intermediately ageddonors. In mesenchymal stem cells from elderly donors however,osteoblastogenesis was greatly diminished in an inflammatory environment whereasadipogenic differentiation remained unchanged.Conclusively, moderate levels of inflammatory stimuli are being interpreted bymesenchymal stem cells at young age as instructive signals for osteoblastogenesis,whereas at old age, an inflammatory milieu may effectively suppress boneremodeling and repair by tissue-borne mesenchymal stem cells while uninterruptedadipogenic differentiation may lead to adipose upgrowth.